Psych Reference · PsychDispo

⚠️ Personal study reference — evidence-based / textbook-sourced. Not clinical advice. Verify doses before use.

Assessment & Clinical Skills

Interview → differential workup → safety & legal → scholarly writing

Interview & Mental Status

Differential & Screening

Safety, Capacity & Legal

Scholarly Writing

Mental Status Exam Clinical Skill

The MSE is the psychiatric "physical exam" — a structured cross-section of the patient's presentation at the moment of interview. Standard domains:

Domain	What to note	High-yield associations
Appearance	Apparent vs. stated age, build, grooming/hygiene, dress, odor, ID markings	Aged appearance: chronic illness/substance use. Lanugo/parotid enlargement/knuckle callus → eating disorder. Long sleeves → IVDU. Self-cutting scars → borderline.
Behavior / Motor	Activity level, agitation vs. retardation, eye contact, gait, abnormal movements, cooperation	Psychomotor retardation → MDD/catatonia. Akathisia (inner restlessness). EPS (dystonia, parkinsonism, TD). Tics → Tourette. Catatonia (waxy flexibility, echopraxia, negativism).
Speech	Rate, rhythm, volume, latency, fluency, articulation	Pressured (rapid, uninterruptible) → mania. ↓amount/latency → depression. Distinguish thought-process disorder from aphasia.
Mood / Affect	Mood = subjective (their words); Affect = observed (range, congruence, stability, reactivity)	Affect: full/restricted/blunted/flat; labile; congruent vs incongruent. Mood-incongruent psychotic features → consider schizoaffective.
Thought process	How thoughts are organized (form/flow)	Circumstantial (eventually reaches point) · tangential (never gets there) · flight of ideas (mania) · loose associations / derailment / word salad (psychosis) · thought blocking · clang (mania) · neologisms · perseveration
Thought content	What they think about	Delusions (fixed false beliefs — persecutory, grandiose, somatic, reference, control, nihilistic), overvalued ideas, obsessions (ego-dystonic), phobias, SI/HI
Perception	Illusions, hallucinations (auditory/visual/tactile/olfactory/gustatory), derealization/depersonalization	Visual/tactile/olfactory → think medical/organic, delirium, substance. Hypnagogic/hypnopompic → narcolepsy/normal.
Cognition	Level of consciousness, orientation, attention (serial 7s, WORLD backward), memory, fund of knowledge, abstraction, MMSE/MoCA	Fluctuating consciousness + inattention → delirium. Concrete proverb interpretation → psychosis/low cognition.
Insight & Judgment	Awareness of illness/need for treatment; decision-making & consequence recognition	Poor insight → psychosis, mania, anosognosia; affects adherence

Describing the tricky domains — terms defined

Speech (describe the form, not the content)

Parameter	What it means	How you'd write it
Rate	Speed of speech	slow · normal · rapid
Volume	Loudness	soft/hypophonic · normal · loud
Quantity / spontaneity	How much, and whether offered freely	talkative/verbose · normal · paucity (only answers, no elaboration)
Latency	Pause before responding	↑ latency → depression, psychosis, guardedness
Rhythm / prosody	Melody & inflection	normal · monotone · dysprosodic
Pressured	Rapid, ↑amount, hard to interrupt	→ mania
Fluency / articulation	Word-finding & clarity	fluent vs non-fluent (aphasia); clear vs dysarthric/slurred

Example: "soft, slow, with increased latency and paucity of speech" (depression) vs "loud, rapid, pressured, difficult to interrupt" (mania).

Affect — describe 6 features (mood = what they say; affect = what you see)

Quality: euthymic, dysphoric, depressed, anxious, irritable, euphoric
Range (the restricted→flat spectrum — see below)
Stability: stable vs labile (rapid, abrupt shifts)
Congruence: does affect match the stated mood AND the thought content/circumstances? (e.g., laughing while describing suicidal thoughts = incongruent/inappropriate)
Reactivity / mobility: reactive (shifts appropriately during interview) vs fixed/non-reactive
Appropriateness to the situation

Range term	What it means (decreasing expressiveness →)
Full / euthymic	Normal range & intensity of emotional expression
Restricted / constricted	Mild–moderate reduction in range (fewer emotions shown). The two are used largely interchangeably; "constricted" often implies a slightly milder reduction than "restricted."
Blunted	Marked reduction in the intensity of expression (severe — but some expression remains)
Flat	Virtual absence of expression — monotone voice, immobile/expressionless face

Memory hook: restricted/constricted = narrowed range; blunted = dampened intensity; flat = nearly none. Example: "Affect constricted in range, dysphoric in quality, congruent with stated depressed mood, reactive."

Thought process — glossary

Term	Definition
Linear / goal-directed	Normal — logically reaches the point
Circumstantial	Over-inclusive detail/digressions but eventually reaches the point
Tangential	Wanders off and never returns to the point
Flight of ideas	Rapid jumping between connected ideas (mania)
Loose associations / derailment	Shifts between ideas with no logical connection (psychosis)
Word salad / incoherence	Incomprehensible jumble of words (severe psychosis)
Thought blocking	Abrupt stop mid-thought, content lost
Perseveration	Repeating the same response/idea regardless of stimulus
Clang / neologism / echolalia	Rhyme-driven links (mania) · invented words · repeating others' words

Insight & Judgment — how to grade and phrase it

Insight = awareness of being ill and needing treatment. Grade good / fair / limited / poor / absent. Ask: do they recognize they have a condition, that the symptoms are part of it, and that treatment can help? (Poor/absent in psychosis, mania, anosognosia → affects adherence.)
Phrase: "Limited insight — attributes symptoms to others rather than illness."
Judgment = ability to make sound decisions and anticipate consequences. Assess from recent real-world behavior (not hypothetical "what would you do with a found letter"). Grade good / fair / impaired.
Phrase: "Judgment impaired — left against medical advice despite active suicidal ideation."

Thought process vs. aphasia: thought disorders preserve syntax/prosody and don't impair reading/naming/repetition; neologisms are symbolic & repeated. Aphasias drop connecting words (telegraphic), impair repetition/naming/comprehension; neologisms are random. Word salad ≈ Wernicke's aphasia.

Medical Mimics of Psychiatric Illness Differential

Scope: Canonical organic differential for new or atypical psychiatric presentations. Neurologic syndromes with psychiatric features → Disorders → Neuropsychiatry. Delirium & hospital encephalopathies → C-L → Delirium. Step 3 rapid triggers → Step 3 → Medical Mimics Rapid.

Many medical conditions present with psychiatric symptoms. Screen hard for an organic cause when there are atypical features — and always before calling a presentation "primary psychiatric."

Red flags for a medical/organic etiology

Late or very early onset (first psychosis >40, first mania in elderly), abrupt onset
Clouded consciousness / fluctuating attention (→ delirium), disorientation, visual/tactile/olfactory hallucinations
Focal neuro signs, seizures, abnormal vitals, autonomic instability, abnormal movements
No personal/family psych history; poor response to standard treatment; cognitive decline

Category	Conditions	Clues / workup
Endocrine	Hypo/hyperthyroidism, Cushing, Addison, hyper/hypoparathyroidism, hypoglycemia, pheochromocytoma	TSH, AM cortisol/dex-suppression, Ca²⁺, glucose, metanephrines
Nutritional	B12/folate, thiamine (Wernicke), niacin (pellagra)	B12/folate; empiric thiamine before glucose in at-risk
Infectious	Neurosyphilis, HIV, Lyme, encephalitis, UTI/sepsis (elderly delirium)	RPR/FTA, HIV, LP; UA in elderly
Autoimmune	Anti-NMDA-receptor encephalitis, SLE/CNS vasculitis, Hashimoto encephalopathy, paraneoplastic/limbic	Anti-NMDAR & paraneoplastic Ab, ANA, anti-TPO, LP, EEG, MRI; young woman + psychosis + seizures/dyskinesia → ovarian teratoma workup
Neurologic	Temporal lobe epilepsy, TBI, stroke, MS, Wilson disease, Huntington, NPH, tumor, delirium	MRI, EEG; ceruloplasmin/Kayser-Fleischer (Wilson, <40 yo)
Toxic / metabolic	Heavy metals, CO, acute intermittent porphyria, hepatic/uremic encephalopathy, electrolytes (Na⁺, Ca²⁺)	BMP, LFTs, ammonia, urine porphobilinogen; med review (steroids, anticholinergics, interferon)

First-episode psychosis / mania / catatonia workup: CBC, CMP, TSH, B12/folate, Ca²⁺, HIV/RPR, UDS, pregnancy; MRI brain + EEG if atypical; LP + autoimmune/paraneoplastic antibodies when rapid onset, fever, seizures, dyskinesias, or refractory. Standard differential per Kaplan & Sadock / general hospital psychiatry references.

Rating Scales & Screening Instruments Assessment

Every major evidence-based instrument in one place — click any scale to see how to administer it and how it's scored. Cutoffs are conventional thresholds; the clinical interview remains the diagnostic standard. (S = self-report · C = clinician-rated.)

Depression

PHQ-9 / PHQ-2 — depression screen & severity

Administer S · 9 items (PHQ-2 = first 2), past 2 wk · ~2 min

Stem "Over the last 2 weeks, how often have you been bothered by…" — each scored 0 not at all · 1 several days · 2 >half the days · 3 nearly every day

Items 1. Little interest/pleasure in doing things · 2. Feeling down, depressed, or hopeless · 3. Trouble falling/staying asleep, or sleeping too much · 4. Feeling tired / little energy · 5. Poor appetite or overeating · 6. Feeling bad about yourself / a failure / let self or family down · 7. Trouble concentrating · 8. Moving/speaking slowly, or being fidgety/restless · 9. Thoughts that you'd be better off dead or of hurting yourself

Score 0–27: 5 mild · 10 moderate · 15 mod-severe · 20 severe. ≥10 ~88% sens/spec for MDD. PHQ-2 (items 1–2) ≥3 → give full PHQ-9.

Notes Free/public domain (Pfizer; no permission needed). Item 9 flags suicidal ideation.

MADRS — depression severity (clinician)

Administer C · 10 items, each 0–6

Score 0–60: 0–6 none · 7–19 mild · 20–34 moderate · 35–60 severe. Response = ≥50% reduction; remission ≤10. Less weighted to somatic items than HAM-D.

HAM-D (HDRS-17) — depression severity (clinician)

Administer C · 17 items

Score 0–7 normal · 8–16 mild · 17–23 moderate · ≥24 severe. The classic trial outcome measure.

BDI-II · GDS-15 · EPDS — special populations

BDI-II S · 21 items 0–3 (0–63): 14 mild · 20 moderate · 29 severe

GDS-15 S · 15 yes/no, geriatric (minimizes somatic items): ≥5 suggests depression

EPDS S · 10 items, perinatal: ≥10–13 possible depression; item 10 screens self-harm

Anxiety

GAD-7 — anxiety screen & severity

Administer S · 7 items, past 2 wk · ~2 min

Stem "Over the last 2 weeks, how often bothered by…" — 0 not at all · 1 several days · 2 >half the days · 3 nearly every day

Items 1. Feeling nervous, anxious, or on edge · 2. Not being able to stop or control worrying · 3. Worrying too much about different things · 4. Trouble relaxing · 5. Being so restless it's hard to sit still · 6. Becoming easily annoyed or irritable · 7. Feeling afraid as if something awful might happen

Score 0–21: 5 mild · 10 moderate · 15 severe. ≥10 = positive screen for GAD (reasonable for panic/social/PTSD too). Free/public domain.

HAM-A — anxiety severity (clinician)

Administer C · 14 items each 0–4 (0–56)

Score <17 mild · 18–24 mild–moderate · 25–30 moderate–severe

Bipolar / Mania

MDQ — bipolar screen (with items)

Stem "Has there ever been a period when you were not your usual self and…" (yes/no each):

Items …felt so good/hyper others thought you weren't normal · so irritable you shouted/started fights · much more self-confident · got far less sleep without missing it · more talkative / spoke faster · thoughts raced · easily distracted · much more energy · much more active/did more · more social/outgoing · more interested in sex · did things unusual/excessive/risky · spending got you/family into trouble

Follow-ups Did several of these happen at the same time? · How much of a problem? (none / minor / moderate / serious)

Score Positive = ≥7 "yes" + same period + moderate/serious problem. Screen only (misses many bipolar-II). Free for clinical use.

YMRS — mania severity (clinician)

Administer C · 11 items (7 scored 0–4, 4 scored 0–8)

Score 0–60: ~≥12 threshold for mania, ≥20 significant; tracks treatment response.

Trauma / PTSD

PCL-5 · PC-PTSD-5 — PTSD screen/severity (with items)

PC-PTSD-5 S · first confirm exposure to a traumatic event, then "In the past month have you…" (yes/no): 1. had nightmares about it or thought about it when you didn't want to · 2. tried hard not to think about it or went out of your way to avoid reminders · 3. been constantly on guard, watchful, or easily startled · 4. felt numb or detached from people, activities, or surroundings · 5. felt guilty or unable to stop blaming yourself or others. ≥3 = positive. Public domain (VA/National Center for PTSD)

PCL-5 S · 20 items 0–4 (0–80) mapped to DSM-5 clusters B/C/D/E: cutoff ~31–33 probable PTSD; tracks response

Gold standard CAPS-5 (clinician structured interview)

OCD

Y-BOCS — OCD severity (clinician)

Administer C · symptom checklist + 10 items (5 obsessions + 5 compulsions), each 0–4

Score 0–40: 0–7 subclinical · 8–15 mild · 16–23 moderate · 24–31 severe · 32–40 extreme (full table in OCD section)

Psychosis

PANSS · BPRS · SIPS

PANSS C · 30 items each 1–7 → positive, negative, general subscales (research standard)

BPRS C · 18–24 items, brief psychiatric symptom rating

SIPS/SOPS C · clinical-high-risk / attenuated psychosis (see Mini-SIPS section)

ADHD

ASRS v1.1 · Vanderbilt · Conners

ASRS v1.1 S, adult · 18 items; Part A (6 items) = screen — ≥4 in the shaded boxes is positive → full evaluation

Vanderbilt Pediatric, parent + teacher versions (cross-informant required)

Notes ADHD is a clinical diagnosis needing onset before 12, ≥2 settings, impairment

Substance Use

CAGE · AUDIT-C · CRAFFT · DAST — substance screens (with items)

CAGE 1 pt each, ≥2 positive: Have you ever felt you should Cut down? · Have people Annoyed you by criticizing your drinking? · Felt Guilty about drinking? · Had a drink first thing in the morning (Eye-opener)?

AUDIT-C 3 items 0–4, ≥4 ♂ / ≥3 ♀: how often you drink · how many drinks on a typical drinking day · how often 6+ drinks on one occasion

CRAFFT adolescent, ≥2 positive: Car (ridden with intoxicated driver) · Relax (use to relax) · Alone · Forget · Family/friends say cut down · Trouble while using

DAST-10 drug-use, ≥3 positive · AUDIT (full 10-item) ≥8 hazardous

CIWA-Ar · COWS — withdrawal severity

CIWA-Ar C, alcohol, 10 items: <8–10 mild · 8–15 moderate · ≥15 severe / impending DTs (drives symptom-triggered benzo dosing)

COWS C, opioid, 11 items: 5–12 mild · 13–24 moderate · 25–36 mod-severe · >36 severe (guides buprenorphine timing)

Eating Disorders

SCOFF · EAT-26 · EDE-Q (with items)

SCOFF 5 yes/no, ≥2 positive: Do you make yourself Sick because uncomfortably full? · Worry you've lost Control over how much you eat? · Lost >One stone (~14 lb) in 3 months? · Believe you're Fat when others say thin? · Would you say Food dominates your life?

EAT-26 S · 26 items: ≥20 → refer for evaluation

EDE-Q S · 28 items over 28 days (severity & subscales)

Dissociation

DES-II · SCID-D

DES-II S · 28 items, each 0–100% → average the items. ≥30 suggests a dissociative disorder (high false-positive — screen only)

Gold standard SCID-D (structured clinical interview for dissociative disorders)

Personality / Borderline

MSI-BPD · PDQ · SCID-5-PD

MSI-BPD S · 10 yes/no McLean Screening Instrument for BPD: ≥7 positive screen

PDQ-4/5 S · screens all PD types (high sensitivity, low specificity → confirm)

Gold standard SCID-5-PD (semi-structured interview)

Cognitive Screening

MoCA — cognitive screen (training required)

Administer C · 30 points, ~10 min · requires free certification/training to administer & use (since 2020)

Score <26 abnormal; +1 point if ≤12 yr education. More sensitive than MMSE for MCI & executive/frontal deficits

Link Training & test at mocacognition.com

SLUMS — cognitive screen (free, no license)

Administer C · 30 points, St. Louis University Mental Status

Score ≥ high-school education: 27–30 normal · 21–26 MCI · <21 dementia. < high-school: 25–30 · 20–24 · <20. Detects MCI; free, no training required

MMSE · Mini-Cog · clock-draw · AD8

MMSE C · 30 points: <24 abnormal (insensitive to MCI/executive; copyrighted)

Mini-Cog (1) register 3 words → (2) clock draw (set hands to 11:10) as distractor → (3) recall 3 words. Score = recall (0–3) + clock (0 or 2). 0–2 = positive screen for impairment. Free

AD8 Informant, 8 items: ≥2 suggests cognitive impairment

Delirium

CAM / CAM-ICU · 4AT · RASS

CAM (1) acute onset & fluctuation + (2) inattention + (3) disorganized thinking OR (4) altered level of consciousness → need 1+2 and (3 or 4)

CAM-ICU / 4AT ICU / rapid bedside versions · RASS = sedation-agitation level (−5 to +4)

Drug-Induced Movement

AIMS · Barnes · Simpson-Angus

AIMS C · 12 items 0–4 for tardive dyskinesia; positive ≈ ≥2 in one item or ≥1 in two items; do q6–12 mo on antipsychotics

Barnes akathisia · Simpson-Angus drug-induced parkinsonism

Sleep

Epworth · ISI · STOP-BANG

Epworth (ESS) S · 8 items 0–3 (0–24): >10 = excessive daytime sleepiness

ISI S · 7 items: 8–14 subthreshold · 15–21 moderate · 22–28 severe insomnia

STOP-BANG 8 yes/no for OSA, ≥3 = intermediate–high risk: Snoring loudly · Tired/daytime sleepiness · Observed apnea · Pressure (HTN) · BMI >35 · Age >50 · Neck >40 cm · Gender male

Suicide · Catatonia · Global

C-SSRS · BFCRS · CGI · WHODAS (with items)

C-SSRS Columbia screen — past month/lifetime (yes/no): 1. Wish to be dead · 2. Non-specific active suicidal thoughts · 3. Thoughts with method (no plan/intent) · 4. Some intent to act · 5. Specific plan and intent · 6. Behavior (any preparatory acts/attempt, ever & in last 3 mo). Yes to 4, 5, or any behavior → high risk. Free with attribution

BFCRS Bush-Francis catatonia: ≥2 of first 14 = positive (see Catatonia)

CGI CGI-S (1–7 severity) & CGI-I (1–7 improvement) · WHODAS 2.0 disability/function

Standard validated instruments (DSM-5-TR measures; APA/USPSTF screening references). PHQ/GAD are free; MMSE & MoCA are copyrighted (MoCA requires certification).

Diagnostic Mnemonics Reference

Classic memory aids for recalling diagnostic criteria — useful at the bedside and on boards. Grouped information is easier to recall than isolated points. Mnemonics prompt criteria; they don't replace the full DSM list or clinical judgment.

Mood / affective

Depression — SIG: E CAPS: Sleep, Interest, Guilt, Energy, Concentration, Appetite, Psychomotor, Suicidality (+ depressed mood)
Mania — DIG FAST: Distractibility, Indiscretion, Grandiosity, Flight of ideas, Activity ↑, Sleep ↓, Talkativeness
Dysthymia — HE'S 2 SAD: Hopelessness, Energy ↓, Self-esteem ↓, 2 years, Sleep Δ, Appetite Δ, Decision/concentration ↓

Anxiety / trauma

GAD — WATCHERS: Worry, Anxiety, Tension in muscles, Concentration ↓, Hyperarousal/irritability, Energy ↓, Restlessness, Sleep Δ
PTSD — TRAUMA: Traumatic event, Re-experience, Avoidance, Unable to function, Month+ of symptoms, Arousal ↑

Medication-effect syndromes

Antidepressant discontinuation — FINISH: Flu-like, Insomnia, Nausea, Imbalance, Sensory disturbance, Hyperarousal
NMS — FEVER: Fever, Encephalopathy, Vital-sign instability, Elevated WBC/CPK, Rigidity
Serotonin syndrome — HARMED: Hyperthermia, Autonomic instability, Rigidity, Myoclonus, Encephalopathy, Diaphoresis

Addiction

Alcohol — CAGE: Cut down, Annoyed by criticism, Guilty, Eye-opener
Substance use disorder — ADDICTeD: Activities given up, Dependence (tolerance), Dependence (withdrawal), Intrapersonal consequences, Can't cut down, Time-consuming, Duration/amount > intended

Delirium

Causes — I WATCH DEATH: Infection, Withdrawal, Acute metabolic, Trauma, CNS pathology, Hypoxia, Deficiencies, Endocrinopathies, Acute vascular, Toxins/drugs, Heavy metals
Life-threatening causes — WWHHHHIMPS: Wernicke's, Withdrawal, Hypertensive crisis, Hypoperfusion/hypoxia, Hypoglycemia, Hyper/hypothermia, Intracranial process, Meningitis/metabolic, Poisons, Status epilepticus

Personality disorders

Disorder	Mnemonic
Paranoid	SUSPECT — Spousal infidelity suspected, Unforgiving, Suspicious, Perceives attacks, Enemy/friend doubts, Confiding feared, Threats in benign events
Schizoid	DISTANT — Detached affect, Indifferent to praise/criticism, Sexual interest low, Tasks solitary, Absent close friends, Neither desires relationships, Takes pleasure in few activities
Schizotypal	ME PECULIAR — Magical thinking, unusual Experiences, Paranoid ideation, Eccentric, Constricted affect, Unusual thinking/speech, Lacks friends, Ideas of reference, Anxiety in social situations, Rule out psychosis
Antisocial	CORRUPT — Conform to law (cannot), Obligations ignored, Reckless disregard for safety, Remorseless, Underhanded, Planning insufficient (impulsive), Temper
Borderline	IMPULSIVE — Impulsive, Moodiness, Paranoia/dissociation under stress, Unstable self-image, Labile relationships, Suicidal gestures, Inappropriate anger, Vulnerability to abandonment, Emptiness
Histrionic	PRAISE ME — Provocative/seductive, Relationships seen as more intimate, Attention-seeking, Influenced easily, Speech impressionistic, Emotions shifting/shallow, Make-up/appearance focus, Emotions exaggerated
Narcissistic	GRANDIOSE — Grandiose, Requires attention, Arrogant, Need to be special, Dreams of success/power, Interpersonally exploitative, Others' feelings unrecognized, Sense of entitlement, Envious
Avoidant	CRINGES — Criticism/rejection preoccupation, Restraint in relationships, Inhibited in new relationships, Needs to be sure of being liked, Gets around occupational contact, Embarrassment prevents risk, Self viewed as inferior
Dependent	RELIANCE — Reassurance required, Expressing disagreement hard, Life responsibilities assumed by others, Initiating projects hard, Alone (helpless), Nurturance sought, Companionship sought urgently, Exaggerated fears of self-care
OCPD	SCRIMPER — Stubborn, Cannot discard objects, Rule-obsessed, Inflexible, Miserly, Perfectionistic, Excludes leisure, Reluctant to delegate

Source: Caplan JP, Stern TA. "Mnemonics in a nutshell: 32 aids to psychiatric diagnosis." Current Psychiatry 2008;7(10):27–33. Confirm against full DSM-5-TR criteria.

Clinical Calculators Reference

The formulas we reach for most in psychiatric/consult practice. (For the QTc formula-selection framework, see the QTc section.)

Calculator	Formula	Use / cutoffs
QTc (Bazett)	QT / √RR (RR sec = 60/HR)	Drug cardiac safety; >500 ms or +60 ms = high TdP risk. Choose the formula by HR — see QTc section
Creatinine clearance (Cockcroft-Gault)	[(140−age) × wt(kg) × 0.85 if ♀] / (72 × SCr)	Renal dosing (lithium, gabapentinoids, paliperidone); avoid lithium if CrCl <30
Anticholinergic burden (ACB scale)	Sum of agent scores (0–3 each)	Cumulative score ↑ delirium/falls/cognitive risk — esp. elderly (diphenhydramine, TCAs, paroxetine, oxybutynin)
Corrected calcium	Ca + 0.8 × (4.0 − albumin g/dL)	Hypoalbuminemia masks true Ca²⁺ (lithium → hypercalcemia; Ca²⁺ affects mood)
Corrected sodium (hyperglycemia)	Na + 0.016 × (glucose − 100) (~0.024 if glu >400)	Pseudohyponatremia; relevant to SIADH (SSRIs, carbamazepine)
Anion gap	Na − (Cl + HCO₃) (normal 8–12)	Toxic ingestions (salicylate, toxic alcohols), metabolic acidosis
Serum osmolality / osmolar gap	2·Na + glucose/18 + BUN/2.8; gap = measured − calc	↑ osmolar gap → toxic alcohols (methanol, ethylene glycol)
MME (morphine equivalents)	Σ(dose × conversion factor)	Opioid risk; see Dose Equivalents (methadone non-linear)
NNT / NNH	1 / ARR (NNH = 1 / ARI)	Translate trial effect size to practice
BMI	wt(kg) / height(m)²	Metabolic monitoring; eating-disorder severity
Child-Pugh / MELD	Bilirubin, albumin, INR, ascites/enceph (CP); Cr/bili/INR/Na (MELD)	Hepatic impairment → dosing; transplant listing

Validated withdrawal/severity instruments — CIWA-Ar (alcohol), COWS (opioid), chlorpromazine/olanzapine-equivalents — are covered in their own sections. Standard clinical references (Cockcroft-Gault 1976; ACB scale; MDCalc-type formulas).

Risk Assessment — Suicide & Violence Clinical Skill

Scope: General framework for stratifying and lowering acute suicide and violence risk (ED, outpatient, inpatient psych). Inpatient medical/C-L setting → C-L → Suicide Risk (Hospital). Chronic aggression pharmacotherapy → Disorders → Aggression & Violence. Acute agitation PRN dosing → Emergencies → PRNs.

The goal isn't to predict — it's to stratify acute risk and lower it. We can only meaningfully move acute risk, and we do it by mitigating dynamic (modifiable) risk factors and building protective factors. The standard of care is an adequate, documented assessment, not accurate prediction.

The framework: chronic vs acute risk

Chronic (baseline) risk = STATIC factors — history we cannot change (prior attempts, sex, trauma, diagnosis). They set the baseline, not the disposition.
Acute risk = the DYNAMIC, modifiable state layered on top of that baseline — this is what we treat.
We lower acute risk two ways:
- Mitigate dynamic risk factors — treat the depression/psychosis/mania, agitation, insomnia, panic/akathisia; detox; treat pain; stop the precipitant.
- Build protective factors / safety plan (below).

Lowering risk through protective factors (the disposition work)

Establish outpatient follow-up (a real, dated appointment — bridge/transition care)
Get the patient on / optimize medications
Collaborate with case management (housing, benefits, transportation, linkage)
Mobilize social support (family/friends engaged in the plan)
Means restriction — remove firearms, provide gun locks, secure/limit medication quantities, restrict access to other lethal means (confirm & document removal)
Strengthen the therapeutic alliance and future orientation

Acute risk levels & disposition

Acute HIGH risk = immediate/imminent risk — the person cannot remain safely even on a locked unit without a dedicated 1:1 (constant observation).
Acute MODERATE — most patients downgrade to this once in the contained ED/unit environment; needs admission/close observation, and consider a 1:1 based on clinical judgment (e.g., persistent intrusive ideation, agitation, impulsivity, or intoxication) rather than treating 1:1 as automatically off the table.
Acute LOW — safe for discharge with outpatient follow-up + safety plan + means restriction.
Placement implication: a receiving/outside inpatient unit reads "needs 1:1" as a very acute patient and will hesitate to accept — so document the trajectory (e.g., "high on arrival, downgraded to moderate in ED after containment/sobriety") to support transfer.

Most indicative RISK factors

Prior suicide attempt — strongest single predictor (lethality/severity of prior attempts > number)
Active SI with a plan + intent + access to lethal means (esp. firearms)
Hopelessness
Recent admission/discharge (week after admit; month after discharge)
Command hallucinations / mood-congruent delusions (↑~5×)
Acute substance use/intoxication (disinhibition) — + major affective disorder ↑~10×
Severe anxiety/panic/akathisia, global insomnia, agitation (modifiable — treat now)
Recent major loss/humiliation; impulsivity (cluster B)
Violence: past violence is the best predictor; active psychosis with a threat/command; intoxication

Most indicative PROTECTIVE factors

Responsibility to family / dependent children <18 — the #1 protective factor
Strong social support & an engaged therapeutic alliance
Future orientation / reasons for living
Help-seeking and treatment engagement/adherence
Religious/moral objection to suicide; fear of death or the act
Means restriction already in place; pregnancy

Key epidemiology

Lifetime completed suicide: affective illness ~15%, schizophrenia ~10%, borderline 5–18%, antisocial ~5%, alcoholism 3–10%
Risk highest the week after admission, month after discharge (42% of completed suicides within 6 mo of discharge), and in early recovery
~⅔ of inpatient suicides had denied intent shortly before death; depression predicts ideation, but anxiety + poor impulse control predict attempts
Lithium: bipolar patients ~7× less likely to attempt (anti-suicide); abrupt stop → fatalities rose ~13×
Methods: firearms 55–60%; hanging (most common in psychiatric hospitals); jumping (general hospitals)

Assessment approach: build rapport first; use a graded "suicide ladder" (wish to be dead → thoughts → method → intent → how close have you come). Probe lethality, planning, precautions against discovery, and feelings afterward (relief vs regret). Don't accept disavowal at face value once a patient has decided to die — look for objective improvement and involve collateral. No-suicide contracts are NOT protective (>½ of inpatient suicides had one). Respond in proportion to risk; document risk level, reasoning, and the modification plan.

Psychosis-Risk Screening (Mini-SIPS / APS) Clinical Skill

The Mini-SIPS (abbreviated Structured Interview for Psychosis-risk Syndromes) screens for DSM-5 Attenuated Psychosis Syndrome (APS) — psychotic-like symptoms below full-disorder threshold that connote risk for future psychosis. APS only applies if the person has never been fully psychotic.

Three symptom classes queried

Delusion-like (DEL): unusual thoughts, suspiciousness/paranoia, ideas of reference, grandiosity, thought interference, magical thinking
Hallucination-like (HAL): attenuated perceptual disturbances (auditory murmurs, visual ambiguities) — not formed, distinct, or fully real
Disorganized communication (DIS): vague, circumstantial, or tangential speech

Rate the most severe symptom in each class against Normal / APS / Psychotic anchors based on content + distress + functional interference.

APS diagnosis — all must be true

Symptom currently in the APS severity range (below psychotic threshold; insight relatively maintained)
Occurs on average ≥1×/week
Onset or worsening in the past year
Distressing/disabling enough to warrant clinical attention
Not better accounted for by another disorder (e.g., panic, depression)
Patient has never been fully psychotic

Why it matters: identifying APS / clinical-high-risk states allows monitoring and early intervention before conversion to a full psychotic disorder. APS frequently co-occurs with other diagnoses; give the APS label only when the attenuated symptoms aren't fully explained by the comorbid condition. Source: Mini-SIPS 1.0 (Woods, Walsh, Cannon, 2020).

Capacity to Consent Clinical Skill

Capacity is decision-specific and clinically determined (competence is a legal determination). A patient can have capacity for one decision and not another, and capacity can fluctuate. The threshold rises with the risk/complexity of the decision (a sliding scale).

The four functional components (Appelbaum & Grisso)

Communicate a choice — express and maintain a stable preference (not vacillating to the point that no decision can be implemented).
Understand the relevant information — the diagnosis, the proposed treatment, alternatives (including no treatment), and their risks/benefits. Assess by asking the patient to paraphrase in their own words.
Appreciate the situation and its consequences — apply that information to themselves (acknowledge they have the condition and that the consequences would actually happen to them). Failure here is classic in psychosis or denial ("the doctors are wrong, I'm not ill").
Reason — rationally manipulate the information: weigh options, compare risks/benefits, and arrive at a choice through a logical process (the focus is on the process, not whether you agree with the outcome).

Key principles: a patient may refuse treatment and still have capacity — an "irrational"-seeming choice is not itself incapacity. Mental illness ≠ incapacity. When capacity is lacking and treatment is needed, proceed via surrogate/proxy, advance directive, or court as appropriate. Reassess as the clinical picture changes (e.g., after delirium clears). Source framework: Appelbaum PS, NEJM 2007 (synthesized).

Capacity vs competence & the consult in practice

Capacity = the clinical ability to make a specific decision at a moment in time (any physician can assess). Competence = a court determination, typically when impairment is expected to be permanent
Lacks capacity → the decision passes to the surrogate/POA
A refusal to engage is not a demonstration of capacity. If the patient won't answer questions, they have not shown they understand/appreciate/reason — so you cannot clear them to leave AMA.
Orientation alone ≠ capacity — a patient oriented ×3 (e.g., in partial-complex status epilepticus) can still lack it. Conversely, a patient may hold a delusional belief (denies their cancer) yet still have capacity to consent to the needed treatment — capacity is decision-specific.
Screen the reversible confounders before concluding: delirium, depression, and intoxication/withdrawal (e.g., immediately after large benzo doses for CIWA). Check consistency with the patient's previously stated values/wishes.
Documentation: if the patient lacks capacity, clearly document it — do NOT complete a pink slip (incapacity ≠ involuntary psychiatric commitment). For "capacity to refuse SNF/placement," obtain PT/OT first. Stay alert to racial/ethnic bias in who gets a capacity consult.

Source: Brandstetter, "Capacity Evaluation," 2024 (synthesized).

Involuntary Admission ("Pink Slip") Clinical Skill

Emergency civil commitment lets a qualified person hold someone for psychiatric evaluation when mental illness creates a substantial risk of harm. Specifics (who can sign, hold duration, exact criteria) vary by state — the framework below uses Ohio as the worked example; always apply your own jurisdiction's statute.

Two things must both be true

Mental illness — a substantial disorder of thought, mood, perception, orientation, or memory that grossly impairs judgment, behavior, capacity to recognize reality, or ability to meet the ordinary demands of life
AND substantial risk of harm by one of the objective criteria (below)

The behavior must result from the mental illness
Delirium / acute medical illness alone does not qualify (though it does not block admission to a psychiatric unit — it may just not be insurance-covered)
Intoxication does not automatically preclude assessment

Objective criteria — need ≥1

Harm to self — threats or attempts at suicide or serious self-inflicted injury
Harm to others — homicidal/violent behavior, threats causing reasonable fear, or present dangerousness
Grave disability — cannot provide for basic physical needs AND those provisions are not available in the community (think advanced dementia)
Would benefit from hospitalization AND behavior poses imminent risk to substantial rights of self/others (think mania)

Who can initiate & what to document

In Ohio: any licensed physician, a health officer, a licensed clinical psychologist, or a police/parole officer
Legibly write and sign name, title, and license/badge number
Document: the organization, date/time, statement of belief, objective support of mental illness, and the risk criterion met
Only a physician (usually a psychiatrist) or clinical psychologist completes the post-transfer evaluation stating reasons to admit or discharge

After the hold expires (Ohio: 72 business hours, ending ~1800 on the 3rd work day): (1) discharge if no longer meeting criteria; (2) convert to voluntary admission (patient may later request discharge in writing → physician has 72 business hours to act); or (3) pursue probate-court civil commitment via affidavit for continued involuntary treatment. State statutes differ — verify locally.

Writing a Case Report — CARE Checklist Scholarly

Case reports sit low on the evidence hierarchy but remain valuable for novel observations and teaching ("the best teaching of medicine is that taught by the patient himself" — Osler). The CARE guideline standardizes what to report so a case is rigorous and reproducible.

#	Section	What to include
1	Title	Primary diagnosis/intervention + the words "case report"
2	Key words	2–5 terms (include "case report")
3	Abstract (no refs)	What's unique & what it adds; main symptoms/findings; diagnoses, interventions, outcomes; take-away
4	Introduction	1–2 paragraphs on why the case is unique (may cite references)
5	Patient information	De-identified data; primary concerns/symptoms; medical, family & psychosocial history (incl. genetics); relevant past interventions & outcomes
6	Clinical findings	Significant exam & important clinical findings
7	Timeline	Historical & current information for this episode, organized chronologically
8	Diagnostic assessment	Testing (exam/labs/imaging); diagnostic challenges; diagnosis & differentials; prognosis/staging where applicable
9	Therapeutic intervention	Type; administration (dose, strength, duration); changes with rationale
10	Follow-up & outcomes	Clinician- & patient-assessed outcomes; follow-up tests; adherence & tolerability; adverse/unanticipated events
11	Discussion	Strengths & limitations; relevant literature (with refs); scientific rationale for conclusions; one-paragraph take-away
12	Patient perspective	The patient's own view of the treatment, in 1–2 paragraphs
13	Informed consent	Obtain it; provide if requested

To appraise a case report's quality, check that it hits these CARE elements — especially a clear timeline, de-identification, documented adverse events, a balanced strengths/limitations discussion, and explicit informed consent. Source: CARE Case Report Guidelines (care-statement.org), CC BY-NC-ND.

Treatment Algorithms

Step-by-step pharmacotherapy decision trees — not diagnostic overviews

Chapter 2 vs Chapter 5: This chapter is medication algorithms (what to prescribe next). Chapter 5 — Disorders covers diagnostic criteria, clinical pearls, psychotherapy, and neuromodulation by syndrome.

Using Algorithms — Principles Evidence-Based Practice

The algorithms that follow are from the Psychopharmacology Algorithm Project at Harvard South Shore (D.N. Osser et al.). They distill the evidence base into decision support — aids to judgment, not cookbook recipes.

Why evidence-informed practice

Three common sources of harm:

Repeating past ineffective/harmful treatments — from not knowing the treatment history
Slips — careless omissions
Errors — not knowing or not applying the evidence

Evidence-based medicine is the "best way we have" — but laborious: diagnose by DSM-5 → identify comorbidity → get the past-treatment history → apply the pertinent research.

Bias-prone defaults people use instead:

Intuition / "the art"
The availability and affective heuristics
Novelty-seeking

"Clinical experience" can be making the same mistakes with increasing confidence — actuarial (evidence-based) decisions consistently outperform impressionistic ones.

Qualities of a good algorithm

Peer-reviewed; published in quality journals
Updated promptly as new treatments emerge
Free of bias — check funding/disclosures
Weighs short- and long-term safety
Not rigid — other options considered at each node
Accounts for comorbidity

Why the outcome evidence is only modest: trials test whole algorithms vs. usual care (diluting the impact of the few critical nodes), and clinicians can skip the most important steps (e.g., clozapine after two failed trials). Physicians deviate when they lack knowledge of the evidence, the recommended drug is unfamiliar or off-formulary, or the evidence-based path takes more time. "Principles are aids to judgment, not laws" — von Clausewitz, applied to psychopharmacology.

Schizophrenia Algorithm

Comorbidities to consider at every node: suicidality, aggressiveness, agitation, negative symptoms, major depression, childbearing potential, substance abuse, cardiac disease, old age. Plasma level monitoring is used for this and all further trials.

1First antipsychotic trial (monotherapy)

Aripiprazole 10–30 mg/day (start 10–15)
Risperidone 2–6 mg/day
Lurasidone 40–160 mg/day (with ≥350 kcal)
Ziprasidone 40–80 mg bid (with ≥500 kcal)
(Amisulpride — not available in US)

NOT clozapine, olanzapine, or quetiapine first. Adequate trial = 4–6 wk at therapeutic dose; check a plasma level.

Poor adherence → long-acting injectable · inadequate trial (other reasons) → alternative first-line agent

↓

adequate trial but unsatisfactory

2Second antipsychotic trial

Risperidone 2–6 mg or olanzapine 10–20 mg, or
a first-generation antipsychotic (e.g., haloperidol 5–15 mg)

↓

two adequate trials failed

3Clozapine — the evidence-based step for resistance

Start 12.5 mg → titrate to 300–450 mg/day (max 900)
Target trough ≥350 ng/mL; weekly ANC (REMS)

↓

partial / inadequate response

4Clozapine augmentation

Add aripiprazole 5–15 mg or lamotrigine, or
ECT (best evidence for clozapine augmentation)

↓

still unsatisfactory

5Combinations — try in any order

Keep clozapine + memantine or omega-3
No clozapine: another monotherapy; FGA + mirtazapine; SGA + celecoxib

Bipolar Mania Algorithm

Confirm diagnosis & address medical etiology. Taper/discontinue antidepressants; treat comorbid substance & anxiety disorders. Always consider: pregnancy risks, IM lorazepam ± haloperidol for severe agitation, ECT (if unresponsive/intolerant or prior ECT response), and prior mania treatments.

1Confirm dx · stop antidepressants · treat agitation

Severe agitation: IM lorazepam 2 mg ± haloperidol 5 mg, or IM olanzapine 10 mg / ziprasidone 10–20 mg
Taper/DC antidepressants; treat comorbid substance & anxiety; consider ECT

↓

determine subtype

2Subtype-driven mood stabilizer

Pure (euphoric) mania → lithium 900–1200 mg/day (level 0.8–1.2 mEq/L) — uniquely anti-suicide
Mixed/dysphoric → SGA + valproate (load 20–30 mg/kg → level 50–125 µg/mL)

↓

unsatisfactory

3SGA step (add or switch)

Quetiapine 400–800 mg (>600 for mixed); risperidone 2–6 mg; olanzapine 10–20 mg
Aripiprazole 15–30 mg; ziprasidone 40–80 mg bid (with food); asenapine 5–10 mg bid SL
Add valproate ± lithium
Avoid two antipsychotics together.

↓

still unsatisfactory

4Tiered options

1st tier: risperidone, haloperidol, olanzapine, carbamazepine, valproate
2nd tier: aripiprazole, ziprasidone, asenapine
3rd tier: clozapine (treatment-resistant mania)

Carbamazepine autoinduces — level falls over 2–4 wk; lowers OCP / lamotrigine / antipsychotic levels.

↓

refractory

5Another tier agent or ECT

Try another agent from any tier, or ECT

Bipolar Depression Algorithm

First decision: urgent need for ECT? If yes → ECT recommended; if refused/unsuccessful → consider IV ketamine.

1Urgent need for ECT?

Yes (severe, suicidal, catatonic, psychotic) → ECT
Refused / unsuccessful → consider IV ketamine

↓

not urgent

2Optimize current regimen

Taper/DC inappropriate agents; optimize levels — lithium level >0.8 mEq/L before calling it a failure

↓

cycle through evidence-based agents

3Core five — try up to all

Quetiapine 300–600 mg (BOLDER; works BP-I & BP-II); lurasidone 20–120 mg
Cariprazine 1.5–3 mg; lithium (optimal level 0.6–0.8 mmol/L); lamotrigine → 200 mg (slow titration; maintenance value)
Also FDA-approved: olanzapine-fluoxetine combination

See start/titration schedules below.

↓

unsuccessful → assess mixed / rapid-cycling

4Antidepressant decision

Mixed / rapid-cycling / prior AD-induced mania → avoid antidepressants; add valproate
Otherwise may add bupropion (1st) or an SSRI (2nd) — only on an adequate mood stabilizer

STEP-BD showed no benefit of adjunctive antidepressants; switch risk modest but real.

↓

refractory

5Refractory bipolar depression

Combinations of the core agents + valproate; ECT; IV ketamine

First-line agents — starting & titration schedules

Agent	Effective dose & start/titration	Pros	Cons
Lamotrigine (Lamictal)	Effective 50–200 mg. Start 25 mg qAM ×14 d → 50 mg qAM ×14 d → 100 mg/day (slower with valproate)	Best tolerated; good preventative effect for depression	Slow to work (6–12 wk); Stevens-Johnson syndrome (~1 in 3,000); does not treat mania
Lithium	Optimal level 0.6–0.8 mmol/L (0.4–0.6 in elderly; higher may be needed in mania). Start ER 300 mg qhs ×4–7 d → 600 mg ×4–7 d → 900 mg qhs	Best preventative vs mania, depression, suicide, hospitalization; may protect against dementia, stroke, cardiac disease	Nephrotoxicity (lessened by keeping level ≤0.8); hypothyroidism (10–20%); arrhythmias; toxicity (esp. with drug interactions); diabetes insipidus (10–15%); tremor, imbalance, nausea, thirst, acne, affective flattening
Cariprazine (Vraylar)	Effective 1.5 mg/day. Start 1.5 mg qod ×7–14 d → 1.5 mg/day	Effective in mania (3–6 mg) and depression	Worse for akathisia (better fatigue/metabolic); lower effect size in depression than other SGAs
Lurasidone (Latuda)	Effective 20–120 mg (usual 40–80). Start 20 mg ½ qd ×4–7 d → 20 mg qd ×4–7 d → 40 mg qd. Take with ≥350 cal meal	Among atypicals, best balance of efficacy & tolerability; approved in pediatrics (10–17 for bipolar depression); may improve cognition	Worse for akathisia (better fatigue/metabolic)
Quetiapine (Seroquel)	Effective 300 mg qhs. Start 50 ×1–4 d → 100 ×1–4 d → 200 ×1–4 d → 300 mg qhs	Best acute efficacy; good preventative; best evidence in BP-II, insomnia & anxiety; treats mania (400–800 mg)	Worse metabolic/cardiac/QTc, fatigue, orthostasis (better akathisia); XR = less orthostasis but more next-day sedation

SGAs share class risks: tardive dyskinesia, metabolic syndrome, akathisia, orthostasis, anticholinergic effects, QT prolongation, temperature dysregulation, NMS, and increased mortality in dementia. Source: Osser, "Psychopharmacology Algorithm Project," Carlat Psychiatry Report 18(4), 2020.

Unipolar (Non-Psychotic) Depression Algorithm

Inpatient with severe melancholic depression → consider urgent ECT (if rejected/inadequate → ketamine, then choices below).

1First-line monotherapy (choose by side-effect fit)

Sertraline 50–200 mg (cardiac-safe); escitalopram 10–20 mg
Bupropion XL 150–450 mg (no sexual SE/weight gain; C/I seizure & eating disorder)

Wait 4–6 wk at therapeutic dose; none proven more effective than another.

↓

inadequate response

2Switch or augment (≈ equal — STAR*D)

Switch: another first-line agent; venlafaxine 75–225 mg or mirtazapine 15–45 mg; TMS
Augment: aripiprazole 2–15 mg or quetiapine; lithium; T3 25–50 µg; L-methylfolate (strongest: T3, lithium, aripiprazole)

↓

treatment-resistant → screen comorbidities (table)

3Atypical features?

Yes → MAOI (phenelzine 45–90 mg, selegiline) or SSRI + aripiprazole
No → TCA (nortriptyline, level 50–150 ng/mL); venlafaxine + mirtazapine; ECT augmentation

↓

inadequate

4Highly treatment-resistant

ECT (best for melancholic/psychomotor); esketamine; MAOI

Comorbidity-targeted options

Comorbidity	Options
Chronic pain	TCA (amitriptyline, clomipramine); duloxetine (fibromyalgia, diabetic peripheral neuropathy, musculoskeletal); gabapentin (post-herpetic neuralgia, peripheral neuropathic); pregabalin (post-herpetic neuralgia, spinal injury, neuropathic, fibromyalgia, diabetic neuropathy); carbamazepine
OCD	High-dose SSRI; augment with SGA (risperidone or aripiprazole)
ADHD	Stimulants (methylphenidate, dextroamphetamine); atomoxetine; venlafaxine, desipramine, bupropion
PTSD	Prazosin or doxazosin; SSRI

Psychotic Depression Algorithm

Diagnosis of major depression with psychotic features → assess severity.

1Severely ill / urgent?

Yes → ECT (response ~80–90%, fastest route to remission). High suicide risk → low threshold for inpatient care

↓

not severe, or ECT declined

2Antidepressant + antipsychotic combination

Sertraline 100–200 mg + olanzapine 10–20 mg (STOP-PD), or a TCA + antipsychotic
Use adequate doses of both; antidepressant monotherapy is inadequate

↓

failed one combination

3Switch class or add lithium

Try the other antidepressant class + antipsychotic, or reconsider ECT
Both combinations failed → add lithium

↓

refractory

4Refractory

ECT; clozapine for refractory cases

Panic Disorder Algorithm

Recurrent unexpected panic attacks + ≥1 month of anticipatory worry or avoidance. Start SSRIs low and go slow — these patients are sensitive to early activation.

1First-line: SSRI + CBT

CBT with interoceptive exposure is first-line (alone or combined)
SSRI started low: sertraline 25 mg, escitalopram 5 mg, or paroxetine 10 mg → titrate to therapeutic over weeks

Warn about transient jitteriness; benefits take 4–6 wk. Limit caffeine. Bupropion is not effective for panic.

Severe early distress → short-term benzodiazepine bridge (clonazepam) while the SSRI takes effect, then taper

↓

inadequate response

2Optimize / switch

Maximize SSRI dose; or switch to another SSRI or an SNRI (venlafaxine XR 75–225 mg)

↓

still refractory

3Third-line

TCA (imipramine, clomipramine) or MAOI (phenelzine) — effective but worse tolerability
Address comorbid agoraphobia with sustained exposure therapy

APA panic disorder guideline; standard references.

Generalized Anxiety Disorder Algorithm

Consider at each node: insomnia, substance use, women of childbearing potential, pregnancy, elderly, neuropathic pain, major depression, bipolar depression/mania, PTSD. No second-generation antipsychotic until the third trial.

1First-line SSRI / SNRI

Sertraline 50–200 mg, escitalopram 10–20 mg, paroxetine 20–50 mg, or duloxetine 30–120 mg

Partial response → augment (hydroxyzine, pregabalin, or benzo). No SGA until the 3rd trial.

↓

inadequate / no response

2Second SSRI or duloxetine

No response → move to an SNRI (venlafaxine 75–225 mg)
Partial → augment: hydroxyzine, pregabalin 150–600 mg, or benzodiazepine

↓

SNRI trial failed

3SGA augmentation (now permitted)

Quetiapine or risperidone (others not studied; avoid olanzapine); valproate
Buspirone 30–60 mg (no abuse potential, safe in COPD)

↓

still unsatisfactory

4Other options

Buspirone, hydroxyzine, pregabalin, bupropion, benzodiazepine, agomelatine (not US), kava, lavender oil

Obsessive-Compulsive Disorder Algorithm

Note: OCD often requires higher SSRI doses than depression, and longer trials (8–12 weeks).

1First SSRI — high dose, long trial + ERP

Fluoxetine 40–80 mg, fluvoxamine 100–300 mg, or sertraline 100–200 mg × 8–12 wk
May exceed PDR max by up to 100% if tolerated (Ninan). ERP is the core treatment.

Inadequate → check plasma level for nonadherence / rapid metabolism before calling it a failure.

↓

inadequate

2Second SSRI or clomipramine

Different SSRI, or clomipramine 100–250 mg (more cardiac/anticholinergic burden), × 8–12 wk

↓

inadequate

3Augment with low-dose SGA

Risperidone 0.5–3 mg or aripiprazole 5–15 mg — ~⅓ respond; quetiapine is ineffective

↓

refractory

4Novel agents

Memantine, NAC, lamotrigine, riluzole, topiramate, minocycline, celecoxib, ondansetron

↓

still refractory

5Device / neurosurgical

TMS → if inadequate, deep brain stimulation or capsulotomy

Y-BOCS — measuring severity & treatment response

The Yale-Brown Obsessive Compulsive Scale rates the past week with 10 items (5 obsessions + 5 compulsions), each scored 0–4 on the same five dimensions: time occupied, interference, distress, resistance, and control. Obsession subscale 0–20 + compulsion subscale 0–20 = total 0–40.

Total score	Severity
0–7	Subclinical
8–15	Mild
16–23	Moderate
24–31	Severe
32–40	Extreme

Use serial scores to track response (a ≥25–35% reduction is the usual treatment-response threshold in trials). A separate symptom checklist catalogs obsession/compulsion types (contamination, harm, symmetry, hoarding, sexual/religious, checking, washing, counting, ordering). Source: Goodman WK et al., Arch Gen Psychiatry 1989 (Y-BOCS).

Posttraumatic Stress Disorder Algorithm

First assess sleep.

1Address sleep first

Nightmares / hyperarousal → prazosin 1 mg hs → titrate (men to ~20 mg, women to ~10 mg) — slow, to avoid first-dose hypotension
Sleep-onset impaired → trazodone 50–150 mg

↓

address core symptoms

2First-line SSRI + trauma-focused therapy

Sertraline 50–200 mg or paroxetine 20–50 mg (only FDA-approved); venlafaxine 75–225 mg alternative
Prolonged exposure / CPT / EMDR is first-line overall and outperforms meds for core PTSD

↓

partial / no response

3Psychosis? then sequence agents

Psychosis present → add an antipsychotic
Else → 2nd SSRI / SNRI / mirtazapine → then 3rd (incl. nefazodone)

Avoid benzodiazepines — no effect on core symptoms, abuse potential, worse outcomes.

↓

augment by symptom cluster

4Augmentation by cluster

Hyperarousal: quetiapine, clonidine · Re-experiencing: risperidone, aripiprazole, lamotrigine, topiramate
Avoidance: aripiprazole, lamotrigine · All symptoms: prazosin, phenelzine, levetiracetam

Medications & Prescribing

Drug reference, mechanisms, dosing/PK, interactions, monitoring & safety

Quick Reference & Drug Classes

Mechanisms & Neurobiology

Drug Deep-Dives

Dosing, PK & Conversions

Interactions, Monitoring & Safety

Antidepressants — Quick Reference

Usual daily dosage and selective action on neurotransmitters. NE = norepinephrine, 5-HT = serotonin, DA = dopamine, ACH = anticholinergic. (0 = none → +++++ = high)

Generic	Brand	Daily dose	Sedation	ACH	NE	5-HT	DA
imipramine	Tofranil	150–300 mg	mid	mid	++	+++	0
desipramine	Norpramin	150–300 mg	low	low	+++++	0	0
amitriptyline	Elavil	150–300 mg	high	high	++	++++	0
nortriptyline	Aventyl, Pamelor	75–125 mg	mid	mid	+++	++	0
clomipramine	Anafranil	150–250 mg	high	high	0	+++++	0
trazodone	Oleptro	150–400 mg	mid	none	0	++++	0
nefazodone	(generic)	100–300 mg	mid	none	0	+++	0
fluoxetine	Prozac, Sarafem	20–80 mg	low	none	0	+++++	0
bupropion	Wellbutrin	150–400 mg	low	none	++	0	++
sertraline	Zoloft	50–200 mg	low	none	0	+++++	+
paroxetine	Paxil	20–50 mg	low	low	+	+++++	0
venlafaxine	Effexor	75–350 mg	low	none	+++	+++	+
desvenlafaxine	Pristiq	50–400 mg	low	none	+++	+++	+
fluvoxamine	Luvox	50–300 mg	low	low	0	+++++	0
mirtazapine	Remeron	15–45 mg	mid	mid	+++	+++	0
citalopram	Celexa	10–40 mg	low	none	0	+++++	0
escitalopram	Lexapro	5–20 mg	low	none	0	+++++	0
duloxetine	Cymbalta	20–80 mg	low	none	+++	+++	0
vilazodone	Viibryd	10–40 mg	low	low	0	+++++	0
atomoxetine	Strattera	60–120 mg	low	low	+++++	0	0
vortioxetine	Trintellix	10–20 mg	mid	none	0	+++++	+
levomilnacipran	Fetzima	40–120 mg	low	none	+++	++	0
MAO inhibitors
phenelzine	Nardil	30–90 mg	low	none	+++	+++	+++
tranylcypromine	Parnate	20–60 mg	low	none	+++	+++	+++
selegiline	Emsam (patch)	6–12 mg	low	none	+++	+++	+++

Source: Preston, Quick Reference to Psychiatric Medications (2017). General reference only — verify against prescribing information.

Antipsychotics — Quick Reference

Ortho = orthostatic hypotension; EPS = acute parkinsonism/dystonia/akathisia (not tardive risk); ACH = anticholinergic; Equiv = dose equivalent to 100 mg chlorpromazine.

Generic	Brand	Dose range	Sedation	Ortho	EPS	ACH	Equiv
Low potency
chlorpromazine	Thorazine	50–800 mg	high	high	++	++++	100 mg
clozapine	Clozaril	300–900 mg	high	high	0	+++++	50 mg
quetiapine	Seroquel	150–600 mg	mid	mid	+/0	+	50 mg
High potency
perphenazine	Trilafon	8–60 mg	mid	mid	++++	++	10 mg
loxapine	Loxitane	50–250 mg	low	mid	+++	++	10 mg
fluphenazine	Prolixin	3–45 mg	low	mid	+++++	++	2 mg
haloperidol	Haldol	2–40 mg	low	low	+++++	+	2 mg
pimozide	Orap	1–10 mg	low	low	+++++	+	1–2 mg
risperidone	Risperdal	4–16 mg	low	mid	+	+	1–2 mg
paliperidone	Invega	3–12 mg	low	mid	+	+	1–2 mg
olanzapine	Zyprexa	5–20 mg	mid	low	+/0	+	1–2 mg
ziprasidone	Geodon	60–160 mg	low	mid	+/0	++	10 mg
iloperidone	Fanapt	12–24 mg	mid	mid	+	++	1–2 mg
asenapine	Saphris	10–20 mg	low	low	+	+	1–2 mg
lurasidone	Latuda	40–80 mg	mid	mid	+	+	10 mg
aripiprazole	Abilify	15–30 mg	low	low	++	+	2 mg
brexpiprazole	Rexulti	1–4 mg	low	low	+	+	1 mg
cariprazine	Vraylar	1.5–6 mg	low	low	+	+	1 mg

Acute EPS columns do not reflect tardive dyskinesia risk — all neuroleptics can cause TD except clozapine. Source: Preston (2017).

Bipolar / Mood Stabilizer Quick Reference

Generic	Brand	Daily dose	Serum level
lithium carbonate	Eskalith, Lithobid	600–2400 mg	0.6–1.5 mEq/L
divalproex / valproate	Depakote	750–1500 mg	50–100 mcg/mL
lamotrigine	Lamictal	50–500 mg	—
carbamazepine	Tegretol, Equetro	200–1600 mg	4–10 mcg/mL
oxcarbazepine	Trileptal	1200–2400 mg	—
olanzapine/fluoxetine	Symbyax	6/25–12/50 mg	—

Lithium expressed in mEq/L; valproate in mcg/mL. Many antipsychotics are also used across phases of bipolar disorder.

Bipolar Maintenance Treatment Medication Reference

Maintenance aims to prevent both poles. Agent choice is driven by which pole predominates, acute-phase evidence, and tolerability. CANMAT hierarchical first-/second-line ranking (Yatham et al.):

Tier	Agent	Best preventative role
First-line	Lithium	Prevents any episode, mania & depression; anti-suicide; target 0.6–0.8 mmol/L
	Quetiapine	Prevents both poles; good for index depression, anxiety, insomnia
	Divalproex	Prevents mania (mixed/rapid-cycling); caution in women of childbearing age
	Lamotrigine	Prevents depression (does not prevent mania)
	Asenapine; aripiprazole / arip. OM; quetiapine or aripiprazole + Li/DVP	Prevent mania (aripiprazole limited for depression prevention)
Second-line	Olanzapine	Prevents both poles but metabolic burden (safety concern ↑↑↑)
	Risperidone LAI (mono or adjunct), paliperidone >6 mg	Prevent mania; LAI useful for adherence
	Carbamazepine; lurasidone or ziprasidone + Li/DVP	CBZ prevents both; lurasidone+Li/DVP for depression

Pattern recognition: depression-predominant course → lamotrigine, quetiapine, lurasidone, lithium. Mania-predominant → lithium, divalproex, quetiapine, aripiprazole, asenapine. Lithium and quetiapine are the broadest (both poles). Continue the agent that achieved acute remission whenever possible. Source: CANMAT/ISBD bipolar maintenance ranking (Table 17).

Anxiolytics & Hypnotics — Quick Reference

Benzodiazepines

Generic	Brand	Dose	≈5 mg diazepam
diazepam	Valium	2–10 mg	5 mg
chlordiazepoxide	Librium	10–50 mg	25 mg
clonazepam	Klonopin	0.5–2.0 mg	0.25 mg
lorazepam	Ativan	0.5–2.0 mg	1 mg
alprazolam	Xanax	0.25–2.0 mg	0.5 mg

Other anti-anxiety agents

buspirone (BuSpar) 5–20 mg · gabapentin (Neurontin) 200–600 mg · hydroxyzine (Atarax/Vistaril) 10–50 mg · propranolol (Inderal) 10–80 mg · atenolol (Tenormin) 25–100 mg · guanfacine (Tenex/Intuniv) 0.5–3 mg · clonidine (Catapres/Kapvay) 0.1–0.3 mg · pregabalin (Lyrica) 25–450 mg · prazosin (Minipress) 5–20 mg (nightmares/daytime anxiety)

Hypnotics

Generic	Brand	Dose
temazepam	Restoril	15–30 mg
triazolam	Halcion	0.25–0.5 mg
zolpidem	Ambien	5–10 mg
zolpidem	Intermezzo	1.75 mg
zaleplon	Sonata	5–10 mg
eszopiclone	Lunesta	1–3 mg
ramelteon	Rozerem	4–16 mg
diphenhydramine	Benadryl	25–100 mg
doxepin	Silenor	3–6 mg
suvorexant	Belsomra	15–40 mg

Stimulants & Over-the-Counter

Psychostimulants

Generic	Brand	Daily dose
methylphenidate	Ritalin	5–60 mg
methylphenidate	Concerta	18–54 mg
methylphenidate	Metadate / Methylin / Daytrana / Quillivant XR	5–60 mg
dexmethylphenidate	Focalin	5–40 mg
dextroamphetamine	Dexedrine	5–40 mg
lisdexamfetamine	Vyvanse	30–70 mg
amphetamine/dextroamphetamine	Adderall, Mydayis	5–40 mg
modafinil	Provigil	100–400 mg
armodafinil	Nuvigil	150–250 mg

Over-the-counter

Agent	Daily dose	Use
St. John's Wort	600–1800 mg	depression/anxiety (significant drug interactions)
SAM-e	400–1600 mg	depression
Omega-3 (EPA)	1–2 g	depression / bipolar adjunct
Folic acid	400–800 mcg	depression
L-methylfolate	7.5–15 mg	depression (Deplin Rx form)
N-acetylcysteine	1200–2400 mg	trichotillomania
Chamomile	200–1500 mg	anxiety
5-HTP	300–600 mg	depression

Anti-obsessional (often higher doses than for depression)

clomipramine (Anafranil) 150–300 mg · fluoxetine (Prozac) 20–80 mg · sertraline (Zoloft) 50–200 mg · paroxetine (Paxil) 20–60 mg · fluvoxamine (Luvox) 50–300 mg · citalopram (Celexa) 10–40 mg · escitalopram (Lexapro) 5–30 mg · vilazodone (Viibryd) 10–40 mg · vortioxetine (Trintellix) 10–20 mg

Newer & Targeted Agents Medication Reference

Agent	Mechanism / use	Key points
Esketamine (intranasal) / IV ketamine	NMDA antagonist; treatment-resistant depression, acute suicidality	Rapid antidepressant; dissociation, ↑BP; REMS (2-h monitoring); abuse potential
Brexanolone (IV) / zuranolone (oral)	Neuroactive steroid, GABA-A modulator; postpartum depression	Brexanolone 60-h infusion (REMS); zuranolone 14-day oral course; rapid onset
Dextromethorphan-bupropion (Auvelity)	NMDA antagonist + CYP2D6 inhibitor (boosts DXM); MDD	Rapid onset; avoid other serotonergic/MAOI
VMAT2 inhibitors (valbenazine, deutetrabenazine)	↓ presynaptic dopamine; tardive dyskinesia, HD chorea	First FDA-approved for TD; QT/parkinsonism; do not abruptly stop
Pimavanserin	5-HT₂A inverse agonist (no D₂); Parkinson disease psychosis	No worsening of motor symptoms; QT prolongation
Lumateperone, cariprazine	SGAs; schizophrenia, bipolar depression	Favorable metabolic (lumateperone); cariprazine partial D₃/D₂ agonist
Orexin antagonists (suvorexant, lemborexant, daridorexant)	DORA; insomnia (sleep onset & maintenance)	Less dependence than benzo-receptor agonists; next-day somnolence

FDA labels; recent guideline updates.

Drug Classes & Mechanisms

Brand = Generic, with mechanism annotations.

Antidepressant classes

SSRIs: Celexa=citalopram, Lexapro=escitalopram, Luvox=fluvoxamine, Prozac=fluoxetine, Paxil=paroxetine, Zoloft=sertraline

SNRIs: Cymbalta=duloxetine, milnacipran, Effexor=venlafaxine, Pristiq=desvenlafaxine

Serotonin modulators: Viibryd=vilazodone (5-HT_1A agonist), Trintellix=vortioxetine (5-HT_1A agonist)

Atypical: Wellbutrin=bupropion (NDRI), Remeron=mirtazapine (NE, 5-HT₂, α₂ antagonist)

TCAs: amitriptyline, nortriptyline, doxepin, clomipramine, desipramine, imipramine — inhibit NE & 5-HT reuptake

MAOIs: phenelzine, selegiline, tranylcypromine

Antipsychotics

Typical (D₂ antagonist): Thorazine=chlorpromazine, Haldol=haloperidol (PO/IM), Prolixin=fluphenazine (PO/IM)

Atypical (D₂/5-HT_2A antagonist): Abilify (PO/IM)/Aristada (IM)=aripiprazole, Rexulti=brexpiprazole, Saphris=asenapine, Clozaril=clozapine, Zyprexa=olanzapine (PO/IM), Symbyax=olanzapine/fluoxetine, Seroquel=quetiapine, Vraylar=cariprazine, Latuda=lurasidone, Invega=paliperidone (PO/IM), Risperdal=risperidone/Perseris IM, Geodon=ziprasidone

Mood stabilizers

Lithium · Depakote=valproate (GABA agonist; inhibits Na_v, ↓glutamate release) · Lamictal=lamotrigine (inhibits Na_v) · Tegretol=carbamazepine · Trileptal=oxcarbazepine

ADHD, narcolepsy, insomnia, RLS

ADHD stimulants (block NE & DA reuptake): Adderall/Mydayis=amphetamine/dextroamphetamine, Vyvanse=lisdexamfetamine, Ritalin/Concerta=methylphenidate

ADHD non-stimulants: Strattera=atomoxetine (inhibits NE reuptake), Kapvay=clonidine (α₂ agonist), Intuniv=guanfacine

Narcolepsy: Nuvigil=armodafinil (blocks DA reuptake), Provigil=modafinil, Xyrem=sodium oxybate

Insomnia: Unisom=diphenhydramine (H₁ antagonist), Lunesta=eszopiclone, trazodone (5-HT_2A/C & α antagonist), Ambien=zolpidem

PTSD nightmares: prazosin, doxazosin (α₁ antagonist) · RLS: Mirapex=pramipexole, Requip=ropinirole

Substance use / antidotes

Opioid/EtOH tx: Suboxone=buprenorphine/naloxone, Narcan=naloxone (IM/nasal), Vivitrol=naltrexone (PO/IM), Campral=acamprosate, Antabuse=disulfiram

Benzo overdose: flumazenil (IV, antagonist)

Alzheimer's: Aricept=donepezil (AChE inhibitor), Namenda=memantine (NMDA antagonist)

Neuropathic pain: Cymbalta=duloxetine, Neurontin=gabapentin, Lyrica=pregabalin

Neurotransmitter Systems Neurobiology

The receptor pharmacology behind psychotropic drug effects and side effects (Stahl framework).

System	Key circuits / receptors	Clinical correlates
Dopamine	Mesolimbic, mesocortical, nigrostriatal, tuberoinfundibular; D₁–D₅ (D₂ key)	↑mesolimbic → positive psychotic sx; D₂ blockade → antipsychotic + EPS + ↑prolactin; ↓mesocortical → negative/cognitive (see Dopamine Pathways)
Serotonin (5-HT)	Raphe nuclei → cortex/limbic; 5-HT₁A, 2A, 2C, 3, transporter (SERT)	SERT block → antidepressant/anti-anxiety; 5-HT₂A block → atypical antipsychotic, ↓EPS; 5-HT₃ → nausea; 5-HT₂C → appetite/weight
Norepinephrine	Locus coeruleus; α₁, α₂, β	NET block → antidepressant/attention; α₁ block → orthostasis/sedation; α₂ agonism (clonidine/guanfacine) → ↓arousal, ADHD/PTSD; β-block → performance anxiety
Glutamate	Excitatory; NMDA, AMPA, kainate	NMDA hypofunction theory of schizophrenia; NMDA antagonists (ketamine) rapid antidepressant; memantine in dementia; excitotoxicity
GABA	Main inhibitory; GABA-A (ionotropic), GABA-B	Benzodiazepines/barbiturates/alcohol/Z-drugs → GABA-A → sedation/anxiolysis/anticonvulsant; withdrawal → hyperexcitability/seizures
Acetylcholine	Nucleus basalis (memory); muscarinic, nicotinic	Muscarinic blockade → dry mouth, constipation, blurred vision, urinary retention, delirium; ↓ACh in Alzheimer → cholinesterase inhibitors
Histamine	H₁	H₁ blockade → sedation, weight gain (mirtazapine, low-potency antipsychotics, TCAs)

Side effects = off-target receptor binding: H₁ → sedation/weight · M₁ (muscarinic) → anticholinergic · α₁ → orthostasis · D₂ → EPS/prolactin · 5-HT₂C → appetite. The receptor-binding (Kᵢ) tables for antidepressants and antipsychotics predict these (see Receptor Binding & Antidepressant PK). Stahl, Essential Psychopharmacology framework.

Dopamine Pathways Concept

Four dopamine pathways

Mesolimbic — positive symptoms (overactive) → D₂ blockade helps
Mesocortical — negative symptoms (underactive)
Tuberoinfundibular (TI) — D₂ blockade → ↑prolactin / galactorrhea
Nigrostriatal (NS) — D₂ blockade → EPS (acute dystonia, akathisia, parkinsonism, tardive dyskinesia)

Quick pearls

Clozapine: agranulocytosis (weekly ANC); mostly D₄, little D₂ blockade; for refractory schizophrenia
Risperidone: high D₂ block → ↑prolactin
Quetiapine: lowest D₂ block → used in Parkinson's psychosis
Lurasidone: "Latuda with food-a" (take with ≥350 cal)
Ziprasidone: fewest metabolic SE but QTc

Dose-Dependent Receptor Occupancy Neurobiology

As the dose rises, a drug recruits receptor actions in order of affinity (highest-affinity target first) — so the same molecule behaves differently at low vs high doses. This explains why low-dose quetiapine is a hypnotic and high-dose is an antipsychotic. (Stahl framework; PET-occupancy data.)

Occupancy thresholds (PET)

Dopamine D₂ (antipsychotics)

~65–70% occupancy → antipsychotic efficacy threshold
~>72% → hyperprolactinemia begins
~>78–80% → EPS threshold (the therapeutic window is between these)
Aripiprazole/cariprazine are partial agonists — high occupancy without full blockade (less EPS/prolactin); clozapine/quetiapine give low/transient D₂ occupancy (rationale for low EPS)

Serotonin transporter (SSRIs)

~80% SERT occupancy needed for antidepressant efficacy — reached at the usual starting dose of most SSRIs
→ pushing the dose higher adds little SERT occupancy (diminishing returns) but recruits off-target actions & side effects
OCD needs higher doses (different threshold/duration)

What you recruit as the dose climbs

Drug	Low dose	Medium dose	High dose
Quetiapine	H₁ (25–100) → sedation/sleep	+ 5-HT₂A, α₁, NET (via norquetiapine, ~150–300) → antidepressant/anxiolytic	+ D₂ (≥300–800) → antipsychotic
Trazodone	H₁, 5-HT₂A, α₁ (25–100) → hypnotic	—	+ SERT (150–600) → antidepressant
Mirtazapine	H₁ dominates (7.5–15) → most sedating, ↑appetite	+ α₂, 5-HT₂/₃ block grows (30–45) → relatively less sedating	—
Paroxetine	SERT (10–20)	—	+ NET & muscarinic (40–60) → more anticholinergic
Venlafaxine	SERT (37.5–75)	—	+ NET (≥150) → noradrenergic effects, ↑BP
Bupropion	NDRI (DAT/NET) across the range — no serotonergic action at any dose; seizure risk rises with dose (esp. IR >450)
TCAs	SERT/NET plus H₁ (sedation), muscarinic (anticholinergic), α₁ (orthostasis), Na-channel (cardiotoxic in OD) — present across doses
Clozapine / olanzapine	Broad multireceptor at all doses (D₂, 5-HT₂A, H₁, M, α₁) → sedation & metabolic; low D₂ occupancy explains low EPS
Aripiprazole	D₂/D₃ partial agonist + 5-HT₁A partial agonist + 5-HT₂A antagonist throughout — "dopamine stabilizer"; can cause akathisia
Risperidone	5-HT₂A + D₂ (1–2)	—	↑ D₂ & α₁ (≥4–6) → EPS & prolactin, orthostasis

Clinical payoffs: use low-dose quetiapine/trazodone/mirtazapine as hypnotics (H₁), not antidepressant doses; if you want quetiapine's antidepressant effect you need mid-range (norquetiapine's NET block); raising an SSRI above the SERT-saturating dose mostly buys side effects, not more efficacy; venlafaxine is "SSRI-like" low, SNRI high; aripiprazole's partial agonism is why it can activate (akathisia) rather than sedate. Stahl, Essential Psychopharmacology; D₂/SERT PET-occupancy studies (Kapur, Farde, Meyer).

Receptor Binding & Side-Effect Profiles APA tables

SGA side-effect summary, plus APA relative side-effect grades (+ seldom → +++ often).

Second-generation antipsychotic side effects (quick view)

Drug	Weight gain / metabolic	EPS	Prolonged QTc
Aripiprazole	Low	Low	Low
Clozapine	Very high	Low	Medium
Lurasidone	Low	Medium	Low
Olanzapine	Very high	Low	Medium
Quetiapine	High	Low	Medium
Risperidone	High	High	Medium
Ziprasidone	Low	Low	High

Comparative side-effect rankings (IPAP / TMAP)

EPS: high-potency FGA > mid-potency FGA = risperidone = paliperidone > low-potency FGA > aripiprazole ≥ ziprasidone = asenapine = olanzapine > lurasidone > iloperidone > quetiapine > clozapine
Tardive dyskinesia: FGA > SGA > clozapine
Weight gain: clozapine = olanzapine > low-potency FGA > risperidone = paliperidone = quetiapine > iloperidone > asenapine > mid-potency FGA > high-potency FGA = aripiprazole = ziprasidone = lurasidone
Prolactin / sexual SE: risperidone = paliperidone > FGA > olanzapine > ziprasidone > quetiapine = clozapine > aripiprazole > asenapine > lurasidone > iloperidone

Efficacy: no significant differences except clozapine (superior). First episode: driven by side-effect fit; use a lower FGA dose (~half) to limit EPS. Clozapine: after 2 failed trials — or earlier with suicidality, violence, or substance use; consider after 2 yr of positive symptoms + 5 yr inadequate response. Source: Antipsychotics comparison chart (IPAP/TMAP/PORT).

APA relative side effects — oral antipsychotics

+ = seldom, ++ = sometimes, +++ = often.

Drug	Akathisia	Parkinsonism	TD risk*	↑Prolactin	Anticholinergic	Sedation	QT	Wt gain	Metabolic
Haloperidol	+++	+++	+++	+++	+	+	++	++	+
Fluphenazine	+++	+++	+++	+++	+	+	++	++	+
Chlorpromazine	++	++	+++	+	+++	+++	+++	++	++
Thioridazine	+	+	+	++	+++	+++	+++	++	+
Aripiprazole	++	+	+	+	+	+	+	+	+
Clozapine	+	+	+	+	+++	+++	++	+++	+++
Olanzapine	++	++	+	++	++	+++	++	+++	+++
Quetiapine	+	+	+	+	++	+++	++	++	++
Risperidone	++	++	++	+++	+	++	++	++	++
Paliperidone	++	++	++	+++	+	+	++	++	++
Lurasidone	++	++	++	+	+	++	+	+	++
Ziprasidone	++	+	+	++	+	++	+++	+	+
Iloperidone	+	+	+	++	+	++	+++	++	++
Asenapine	++	+	++	++	+	++	++	++	++
Cariprazine	++	+	+	+	++	++	++	++	+
Brexpiprazole	++	+	+	+	+	++	++	+	++

*Dystonia/tardive grouped from APA Table 6. Clozapine notable: high salivation, severe constipation/ileus possible, rare myocarditis/neutropenia. Source: APA Practice Guideline for Schizophrenia (2020), Tables 5–6.

Receptor binding highlights (APA Table 5): Haloperidol = strong D₂, minimal H₁/muscarinic (→ EPS, little sedation). Clozapine/olanzapine = strong H₁ + muscarinic + broad 5-HT (→ sedation, metabolic, anticholinergic). Aripiprazole/brexpiprazole/cariprazine = D₂ partial agonists. Risperidone/paliperidone = strong α₁/α₂ + D₂ (→ prolactin, orthostasis).

Clozapine — Complete Guide Medication Reference

The only antipsychotic proven superior in treatment resistance and the only one that reduces suicide risk in schizophrenia/schizoaffective disorder — yet underused because of monitoring burden. Indicated after failure of ≥2 adequate antipsychotic trials (or earlier for suicidality, violence, or substance use).

Dosing & response

Supplied 25 & 100 mg (breakable) tablets; ODT and oral suspension exist
Start 12.5 mg qd–bid, ↑ by 25–50 mg/day → target 300–450 mg/day by ~2 wk; max 900 mg/day divided TID
Therapeutic response may take 3–6 months
Target trough plasma level ≥350 ng/mL (>600 → toxicity / seizure risk)
Half-life ~12 h; fluvoxamine/cimetidine/erythromycin ↑ level; carbamazepine & tobacco smoke ↓ level (smoking cessation can ↑ level → toxicity)

Side effects & black-box warnings

Severe neutropenia / agranulocytosis (~0.4%; most in first 3 mo) — REMS/ANC monitoring
Seizures (~5%, dose-related) — reduce dose or add valproate
Myocarditis (rare, often fatal — check troponin/CRP/eos if early fever, tachycardia, dyspnea); cardiovascular collapse ~1/3000
Sedation, dizziness, hypersalivation (towel on pillow; can treat), weight gain (15–30 lb/yr), worst metabolic profile (new diabetes, hyperlipidemia), tachycardia, constipation → ileus (bowel regimen — see Constipation reference)
EPS uncommon; little/no prolactin rise; orthostasis (slow titration); ↑ mortality in elderly dementia (class warning)

ANC monitoring & management of neutropenia (Clozapine REMS)

Before starting: baseline ANC must be ≥1500/µL (general population) or ≥1000/µL for documented benign ethnic neutropenia (BEN). Monitoring frequency: weekly ×6 months → every 2 weeks for months 6–12 → monthly after 12 months of normal ANCs. WBC counts are no longer accepted — submit the ANC.

ANC level (general pop.)	Action	ANC monitoring
Normal ≥1500/µL	Continue treatment	Per phase (weekly → q2wk → monthly)
Mild neutropenia 1000–1499	Continue treatment	3×/week until ANC ≥1500, then resume prior interval
Moderate 500–999	Hematology consult; interrupt if clozapine-induced suspected; resume once ANC ≥1000	Daily until ≥1000, then 3×/week until ≥1500, then weekly ×4 wk
Severe <500	Hematology consult; interrupt; do not rechallenge unless benefits outweigh risks	Daily until ≥1000, then 3×/week until ≥1500

BEN thresholds are lower (continue through mild; interrupt only for ANC <500). Confirm any first ANC <1500 (<1000 for BEN) with a repeat within 24 h. Fever: evaluate for infection and check ANC (rule out neutropenia & myocarditis). A prescriber may continue despite neutropenia with a documented "Treatment Rationale." Severe neutropenia incidence ~0.4%, fatal ~0.012% (1/10,000). Source: Clozapine REMS / "Clozapine and the Risk of Neutropenia," 2019; Carlat Clozapine Fact Sheet.

Consult-liaison management (inpatient)

Re-initiation after missed doses (metabolism resets fast): ≤48 h → resume prior dose. 48–72 h → 50% of prior daily dose day 1, 75% day 2, full dose day 3. 72 h–1 wk → restart 12.5 mg qd–bid, titrate over ~3 days. >1 wk → re-titrate as a new patient (12.5 mg start). Re-initiate promptly at admission to prevent relapse.

Levels & CYP1A2 swings

Metabolized by CYP1A2 → norclozapine; target trough 350–600 µg/L
Systemic inflammation/infection (COVID, pneumonia — ↑CRP/fever) lowers 1A2 → ↑levels/toxicity → reduce dose ≥50%
Smoking induces 1A2; stopping smoking in hospital ↑ levels → consider dose reduction. Fluvoxamine/ciprofloxacin/OCPs ↑ levels; carbamazepine/rifampin/phenytoin ↓ levels
Some East Asians are slow metabolizers — lower doses effective

Adverse-effect management

Sialorrhea: towel on pillow, side-sleeping → ipratropium spray → SL atropine drops → glycopyrrolate → terazosin; botox if refractory
Constipation → ileus (50–80%; can be fatal): ask every visit; docusate → PEG → bisacodyl/senna → mag citrate/enema; hold clozapine + image if obstruction
Seizures (3.5–8%, dose/level-related, >600 mg or >500 µg/L): EEG, add valproate — rarely need to stop clozapine
Myocarditis (1–3%, first ~4 wk, 10–30% mortality): monitor CRP, troponin, eosinophils, HR weekly during titration; chest pain/dyspnea/tachycardia → stop & admit

Don't stop abruptly (unless myocarditis or severe neutropenia) — taper over 1–2 wk to avoid rebound psychosis, cholinergic rebound, and clozapine-withdrawal catatonia (treat by resuming clozapine — even low doses reverse it — plus standard catatonia care). On chemo: continue clozapine if well-established, coordinate alternate ANC monitoring with heme-onc, and consider filgrastim through the neutropenic nadir. Source: ACLP "How-To Guide: Clozapine Consultation" (Lavakumar; updated 2024).

Lithium — Comprehensive Reference Medication Reference

Lithium remains the gold-standard mood stabilizer and is uniquely disease-modifying — it prevents both poles, reduces completed suicide, and lowers all-cause mortality. Its benefit grows with time, so it is a long-term treatment rather than primarily an acute agent.

Five indications

Bipolar maintenance — first-line across guidelines; prevents mania & depression. Acute mania OR ~1.45 vs placebo; weaker for acute bipolar depression
Unipolar depression — antidepressant augmentation in TRD; standalone prevention of recurrent depression (better proven than antidepressants for prevention)
Suicide prevention — the only psychotropic with robust evidence; meta-analytic OR ~0.13 vs placebo; cohort data ~60% ↓ suicide mortality
Mood temperaments — cyclothymia/hyperthymia may respond to ~half-standard doses
Dementia prevention — emerging; may normalize the elevated dementia risk in mood-disorder patients, possibly at very low doses

Predictors of good response (meta-analysis, >12,000 pts)

Mania-depression-interval (MDI) sequence — strongest positive predictor (OR ~4.27)
No rapid cycling (rapid cycling OR ~0.30) and no psychotic features (OR ~0.52)
Family history of bipolar (OR ~1.61); shorter pre-lithium illness; later age of onset
Poorer response: DMI sequence, rapid cycling, psychotic/mixed features, higher BMI

The "classic responder": MDI pattern, no rapid cycling, no psychosis, + family history, later onset.

Dosing & therapeutic drug monitoring

Context	Target serum level (trough, 12 h)	Notes
Acute mania / mixed	0.8–1.2 mEq/L	Start ~300 mg TID (FDA); dose to clinical efficacy, not just a number
Maintenance	0.6–0.8 mEq/L	Consensus across guidelines
Elderly	~0.4–0.6 mEq/L	~half standard; greater sensitivity
Renal impairment	Start lower, titrate slowly	Avoid if CrCl <30 mL/min
Pregnancy	0.6–1.0 mEq/L	Clearance ↑ in pregnancy, drops sharply postpartum — monitor frequently

Monitoring cadence: check level after ~3 days, then weekly until stable, then every 3–6 months; renal function (Cr/eGFR) every 3–6 months; TSH and calcium every 6–12 months; weight periodically. Once-daily dosing and the lowest effective level minimize renal risk. Pre-treatment workup: renal function, electrolytes, TSH, calcium, weight/vitals, pregnancy test, and a review of diuretics/NSAIDs/ACE-ARBs. Lithium has linear PK; 300 mg lithium carbonate ≈ 8 mEq Li.

Adverse effects (mostly dose-related)

Early/transient: fine tremor, GI upset, polyuria/polydipsia, weight gain
Hypothyroidism ~14% over ~6 yr (OR ~5.78; women >60); manage with levothyroxine — not a reason to stop lithium
Hyperparathyroidism ~10% (vs 0.1% baseline) — monitor calcium
Nephrogenic DI — most common renal effect, usually reversible (polyuria/polydipsia)
CKD — GFR ↓ ~0.92%/treatment-yr; clinically significant stage-3 needs ≥6–10 yr exposure (~5% after >20 yr); stage-4 rare. Amiloride may mitigate nephrotoxicity & DI

Toxicity — narrow therapeutic index

Mild (1.5–2.0): coarse tremor, nausea, diarrhea, drowsiness, weakness
Moderate (2.0–2.5): confusion, agitation, ataxia, dysarthria
Severe (>2.5): seizures, coma, CV collapse, renal failure → consider hemodialysis
SILENT = irreversible lithium-effectuated neurotoxicity (persistent cerebellar ataxia/cognitive change)
Triggers: dehydration, low-salt diet, renal impairment, interacting drugs, elderly. Symptoms may not track the level.

Key drug interactions

↑ Lithium level (toxicity risk): thiazide diuretics, NSAIDs, ACE-inhibitors/ARBs, metronidazole (all ↓ renal clearance). ↓ Lithium level: acetazolamide, theophylline, sodium bicarbonate (↑ urinary excretion). Pharmacodynamic: serotonergic drugs → serotonin syndrome
antipsychotics → neurotoxicity (EPS up to NMS)
calcium-channel blockers → neurologic reactions
iodide → hypothyroidism

Pregnancy: historical Ebstein-anomaly fear is overstated — modern data show only a modest rise (any anomaly OR ~1.81; cardiac OR ~1.86 with first-trimester exposure), and the cardiac risk is dose-dependent (>900 mg/day ~3× ; ≤600 mg/day non-significant). Lithium is reasonable in pregnancy for prior severe mania/lithium response — use the lowest effective dose, divided dosing to avoid peaks, frequent levels, fetal echo, and decrease/hold 24–72 h before delivery then resume postpartum. Neonatal: "floppy baby," hypothyroidism, nephrogenic DI.

Never stop abruptly (except true toxicity): abrupt discontinuation carries ~50% risk of mania within a month and ↑ short-term suicide risk. Taper gradually over ≥2 weeks (≈300 mg/week or 25% q2wk) — median time to recurrence 10.6 mo (gradual) vs 3.5 mo (rapid). Rare lithium-discontinuation-induced refractoriness exists, but most patients still respond on reinstitution. Synthesized from lithium clinical reviews (Acta Psychiatr Scand 2019/2022/2023; JAMA 2023; NEJM 2017).

Valproate — Comprehensive Reference Medication Reference

A broad-spectrum mood stabilizer/anticonvulsant (FDA-approved for acute mania/mixed, epilepsy, migraine prophylaxis). Its edge over lithium is in mixed features, rapid cycling, and multiple prior episodes — but it carries severe teratogenicity and metabolic/endocrine burden.

Indications

Acute mania / mixed — FDA-approved; beats placebo (RR ~1.42), ≈ lithium on most outcomes
Bipolar maintenance — better than placebo, but inferior to lithium as monotherapy (BALANCE: Li or Li+VPA > VPA alone)
Bipolar depression — modest benefit (small trials)
Acute agitation — IV (20 mg/kg) ≈ haloperidol with less sedation / no EPS (off-label)
ICU delirium/agitation — adjunct; reduces concomitant psychoactive use

Predictors of good response (CANMAT)

Mixed states (depressive symptoms during mania)
Rapid cycling — positive for valproate, negative for lithium
Multiple prior mood episodes
Depression-mania-euthymia course (opposite of the lithium-favorable MDI pattern)

Dosing & therapeutic drug monitoring

Context	Dose / target	Notes
Bipolar mania (DR)	Start 750 mg/day divided → trough 85–125 µg/mL (max 60 mg/kg/day)	Titrate rapidly
Oral loading	20–30 mg/kg/day → therapeutic in 1–2 days	For acute mania
ER formulation	~25 mg/kg/day once daily	ER is 8–20% lower bioavailability than DR — ↑ total daily dose 8–20% when converting
Epilepsy	Target 50–100 µg/mL	—
Elderly	Start lower, titrate slowly	Watch somnolence, dehydration, intake

Protein binding is concentration-dependent (free fraction ~10% at 40 → ~18.5% at 130 µg/mL) and rises further in the elderly, hyperlipidemic, hepatic/renal patients — total levels can under-represent active drug, so check a free valproate level in these populations.

Three FDA boxed warnings: Hepatotoxicity (fatal, usually <6 mo; highest risk <2 yr old, polytherapy, mitochondrial/POLG disease; ~1/20,000) · Teratogenicity (~9–10% major malformations, NTDs, dose-dependent ↓IQ, ↑autism) · Pancreatitis (hemorrhagic, ~1/40,000). Contraindicated in hepatic disease, POLG/urea-cycle disorders, and migraine use in pregnancy.

Adverse effects

GI (nausea, diarrhea), tremor, sedation, alopecia (reversible), transient ↑transaminases
Weight gain (~50%; mean ~21 kg) with hyperinsulinemia/metabolic syndrome (partly reversible)
PCOS — up to 64–70% develop polycystic ovaries/hyperandrogenism (esp. if started <20 yo); often reverses on switching to lamotrigine/stopping
Hematologic: dose-dependent thrombocytopenia (trough >110 ♀ / >135 ♂), ↓platelet aggregation, acquired von Willebrand
Hyperammonemia — can occur with normal LFTs (lethargy/confusion/vomiting); markedly ↑ with topiramate
↓ bone mineral density; male infertility

Monitoring

Baseline: LFTs, CBC w/ platelets, coagulation, pregnancy test; consider urea-cycle/mito screen if at risk
VPA level after dose changes, then periodically; CBC/LFTs baseline → frequently first 6 mo → periodically
Ammonia only if symptomatic (always check with topiramate)
Weight/BMI & menstrual history each visit; coagulation before surgery/pregnancy
After ~2 yr stable & uncomplicated, routine labs can be relaxed — patient education on warning symptoms beats routine labs for catching hepatotoxicity

Key drug interactions

↓ VPA level: enzyme inducers (phenytoin, carbamazepine, phenobarbital, rifampin) can double clearance; carbapenems (meropenem, ertapenem) drop levels 60–100% in days — avoid
↑ VPA level: felbamate, aspirin (protein-binding displacement)
VPA on others: doubles lamotrigine (inhibits glucuronidation → halve lamotrigine, SJS risk); ↑ phenytoin free fraction; ↑ diazepam; topiramate → hyperammonemia/encephalopathy

Pregnancy — the most teratogenic common psychotropic: ~9–10% major malformations (NTDs, cardiac, oral clefts, hypospadias, limb), dose-dependent IQ loss, ↑ autism, intellectual disability ~6% by age 18 (vs ~1.35%) — present even <1000 mg/day. Avoid in women of childbearing potential (AAN Level A; EMA ban without effective contraception). If unavoidable: document contraception, lowest dose, high-dose folate 4–5 mg/day, thorough counseling.

Valproate vs Lithium — quick contrast

Domain	Valproate	Lithium
Acute mania	Comparable	Comparable
Maintenance monotherapy	Inferior (BALANCE)	Superior
Mixed / rapid cycling	Preferred	Less effective
Suicide prevention	Modest / not significant	Strongest evidence (superior to VPA)
Adherence/tolerability	Fewer dropouts	More dropouts
Teratogenicity	Severe (~10% + IQ/ASD)	Modest (~1.8× cardiac, dose-dependent)
Weight / PCOS	~50% weight gain; PCOS up to 64%	Less weight gain; no PCOS
Organ toxicity	Hepatic, pancreatic, marrow	Renal (CKD), thyroid (~14%)

Bottom line: first-line for acute mania — especially mixed/rapid-cycling/multi-episode; lithium wins for maintenance monotherapy and suicide prevention (Li+VPA combo often strongest). Check ammonia for unexplained lethargy (even with normal LFTs, esp. with topiramate), monitor weight/PCOS in women, and avoid in reproductive-age women unless no alternative. Synthesized from valproate clinical reviews (CANMAT; JAMA 2023; AAN/AES/SMFM; BALANCE; Cochrane 2019).

Lamotrigine — Reference Medication Reference

A mood stabilizer with its niche in bipolar depression prevention (and maintenance) — not acute mania or acute depression. Anticonvulsant; blocks voltage-gated Na⁺ channels, ↓ glutamate release.

Dosing — the titration is the whole game

Monotherapy: 25 mg/day ×2 wk → 50 mg ×2 wk → 100 mg → target 200 mg/day (slow titration ↓ rash risk)
With valproate (inhibits glucuronidation → ↑ lamotrigine ~2×): halve the rate — 25 mg every other day → target ~100 mg
With inducers (carbamazepine, OCPs, rifampin → ↓ lamotrigine): faster titration / higher target (~400 mg)
Restart full titration if ≥5 days missed (see Don't-Stop-Cold)

Adverse effects

Stevens-Johnson syndrome / TEN — risk highest with fast titration, valproate co-use, early treatment; any rash → stop & evaluate (esp. mucosal/systemic)
Benign maculopapular rash common; headache, dizziness, diplopia, ataxia, nausea
Rare: DRESS, HLH, aseptic meningitis
Well tolerated overall: no weight gain, minimal sedation, no routine level/labs

Bottom line: first-line for preventing bipolar depression; ineffective for acute mania (don't use as monotherapy in acute mania) and weak for acute bipolar depression. The valproate interaction (halve the dose/rate) and rash vigilance are the two must-knows. FDA label; CANMAT.

Carbamazepine / Oxcarbazepine — Reference Medication Reference

Anticonvulsant mood stabilizer (FDA-approved for acute mania, esp. mixed/rapid-cycling); blocks Na⁺ channels. Defined by its autoinduction and broad interactions.

Dosing & monitoring

Start ~200 mg BID → titrate; target level 4–12 µg/mL
Autoinduces CYP3A4 — its own level falls over 2–4 wk (re-check & re-dose up)
Baseline + periodic CBC, LFTs, sodium; HLA-B*1502 (Han Chinese/SE Asian) before starting — SJS risk

Adverse effects

Hyponatremia / SIADH (more with oxcarbazepine), agranulocytosis & aplastic anemia (rare), SJS/TEN, hepatotoxicity
Diplopia, ataxia, sedation, nausea; teratogenic (neural tube defects)
Potent 3A4 inducer → ↓ levels of OCPs, lamotrigine, antipsychotics, methadone, warfarin, DOACs

Oxcarbazepine: less autoinduction, no level monitoring, fewer drug interactions, but more hyponatremia; weaker mania evidence. FDA label; standard references.

Long-Acting Injectable (LAI) Antipsychotics Medication Reference

LAIs reduce relapse and rehospitalization (Tiihonen, Leucht) and are underused — favor early in nonadherence, after a first episode, or by patient preference. Always establish oral tolerability first.

Agent	Start	Maintenance / interval	Oral overlap	Notes
Haloperidol decanoate	10–20× oral dose (if >100 mg, split: 100 mg then rest in 3–7 d)	10–15× oral dose q4 wk (max 450 mg)	~3–6 mo (until steady state, ~4 doses)	Deep IM gluteal, 21 G; t½ ~21 d
Fluphenazine decanoate	6.25–25 mg q2 wk (max 100 mg)	12.5–50 mg q2 wk; 12.5 mg ≈ 10 mg/day oral	1–2 wk minimum; until steady state	Gluteal; t½ ~14 d
Aripiprazole monohydrate (Maintena)	400 mg ×1	400 mg (300 if interactions) q4 wk	14 days oral overlap required	≥26 d between doses; ↓dose with strong 3A4/2D6 inhibitors; avoid 3A4 inducers
Aripiprazole lauroxil (Aristada)	441 / 662 / 882 / 1064 mg	Same q4 wk (882 q4–6 wk; 1064 q8 wk)	21 d oral — or single Aristada Initio 675 mg + 30 mg oral ×1	Deltoid (441/675) or gluteal
Paliperidone palmitate (Sustenna)	Day 1: 234 mg, Day 8: 156 mg (deltoid)	39–234 mg q4 wk	None (loading dose covers it)	Trinza q12 wk after ≥4 mo stable on Sustenna; renal metabolism
Risperidone (Consta)	25 mg q2 wk	25–50 mg q2 wk	3 wk oral overlap (no immediate release from microspheres)	Perseris = SC monthly 90/120 mg (no overlap)
Olanzapine (Relprevv)	210–405 mg q2–4 wk	150–405 mg	None	REMS: post-injection delirium/sedation syndrome — observe 3 h; gluteal only

High-yield: Paliperidone Sustenna needs no oral overlap (uses a day-1/day-8 deltoid load). Consta needs 3 weeks of oral overlap. Olanzapine LAI carries a unique post-injection syndrome REMS (3-hour observation). Aripiprazole Maintena needs 14 days of oral overlap (or use Aristada Initio). Source: LAI dosing/practical guides.

Antidepressants — Dosing, Kinetics & Augmentation Prescriber Reference

General principle: one change at a time; contact q1–2 wk; wait 1–4 wk at a dose before escalating total non-response, 8–12 wk if responding gradually. First-line SSRIs = sertraline or escitalopram; bupropion = first-line non-SSRI; fluoxetine the only SSRI FDA-approved in children.

Drug	Start	Titration / target	Notes
Sertraline	50 mg AM (25 if elderly/panic)	↑50 mg q2–4 wk; change if no response at 200 mg ×2–4 wk	One study favored holding 100 mg over going to 200
Escitalopram	10 mg (incl. most elderly/hepatic)	↑20 mg, though fixed-dose trials show no 10-vs-20 difference	10 mg ≈ 40 mg citalopram potency, fewer SE
Citalopram	20 mg (10 if elderly)	↑40 mg after 1 wk; 20 mg may ≈ placebo	QTc: max 40 (<60 yo) / 20 (≥60, hepatic, 2C19 PM, cimetidine). Don't drop dose abruptly (Rector 2016: ↑suicide)
Fluoxetine	10–20 mg AM (5–10 if >60/panic)	↑20 mg q2–4 wk; change if no response at 60 mg	Long half-life; only SSRI w/ no significant weight gain (Uguz 2015)
Bupropion SR	100–150 mg AM	→150 bid after 4–7 d; max SR 200 bid / XL 450	Use SR/XL not HCl (4× seizure rate). C/I seizure, anorexia/bulimia
Venlafaxine SR	37.5 mg AM ×1 wk	→75 → 150 (hold 3 wk); change if no response at 300	HTN 1–2% low dose, up to 10% ≥300 mg — check baseline BP
Duloxetine	40 mg (÷ doses helps nausea)	→60 mg after 3–7 d; 120 no more effective, more toxic	FDA: fibromyalgia, MSK & diabetic neuropathic pain; ↑BP
Mirtazapine	15 mg qPM	→30 mg at 1 wk; 45 = PDR max (no added benefit, Ueno)	Somnolence may be less at higher doses; avoid if weight a concern
Nortriptyline (TCA)	10 mg bid / 25 hs (5 bid elderly)	↑ to 100–150 mg; do not exceed 150	Therapeutic window 50–150 ng/mL; baseline EKG; 10-day supply can be fatal
Tranylcypromine (MAOI)	10 mg bid	→10 tid after 1 wk; ↑q1–3 wk to max 60 mg	Tyramine diet; fewer sexual SE/weight gain than phenelzine
Vilazodone	10 mg ×1 wk	→20 ×1 wk →40 (maintain); take with food	SSRI + 5-HT₁A partial agonist; sedating, GI; no weight gain
Vortioxetine	10 mg	10–20 mg effective	SSRI + 5-HT₃/₇ modulation; signal for pro-cognitive benefit

STAR*D remission rates (sequential trials)

Lack of placebo control limits interpretation, but generalizable to real-world patients.

Level 1 citalopram: 28% remission (response 47%)
Level 2 switch: sertraline 18%, bupropion 21%, venlafaxine 25% · augment: buspirone 30%, bupropion 30% (switch ≈ augment)
Level 3 switch: mirtazapine 12%, nortriptyline 20% · augment: lithium 15%, T3 25%
Level 4 tranylcypromine 7%; venlafaxine + mirtazapine 14%
Relapse of remitters at 12 mo climbs each step: 40% → 55% → 65% → 71%
High baseline anxiety → markedly worse remission at every level

Augmentation — evidence rating & added monthly cost (VA)

Augment	Evidence	$ / mo
Lithium 900 mg (to TCA)	A	$1
T3 25 µg (TCA or SSRI)	A	$2
Aripiprazole 10 mg (to SSRI)	A	$39
Quetiapine 300 mg	A	$3
Risperidone 2 mg	A	$1
L-methylfolate 15 mg	A/B	$120
Mirtazapine 15 mg	A/B	$2
Buspirone 40 mg	B	$3
Bupropion SR 300 mg	B	$6

A = ≥1 RCT. Don't augment a likely placebo partial response (rapid early improvement that plateaus is often placebo).

TCA cautions

Contraindicated: recent MI, ischemic heart disease, conduction defects/BBB, urinary retention, narrow-angle glaucoma, renal failure, orthostasis (nortriptyline = least orthostasis)
Baseline EKG. Overdose = the 3 C's

Key class safety signals

Sexual dysfunction 40–80% (placebo 14%) → switch to bupropion/mirtazapine; sildenafil adjunct (men)
Upper GI bleed OR 1.3–6.3× (↑↑ with NSAIDs/antiplatelets/alcohol); reduce with a PPI
↓BMD / fracture risk ~2× (dose-dependent)
Hyponatremia (SIADH), esp. elderly; suicidality warning ≤24 yo
Citalopram & quetiapine both prolong QTc — caution combined

Receptor binding affinity (K_i, nM) — lower = stronger binding

Drug	SERT	NET	DAT	H1	mACh	α1	5-HT2A	5-HT2C
Paroxetine	0.08	57	574	22000	108	4600	—	—
Sertraline	0.21	667	25.5	24000	625	370	—	—
Fluoxetine	1.0	660	4176	6250	2000	5900	200	255
Citalopram	1.4	5100	28000	380	1800	1550	—	617
Escitalopram	1.8	7180	>10000	1970	1240	3870	—	2531
Fluvoxamine	1.95	1892	>10000	>10000	240000	1288	—	6700
Duloxetine	0.8	5.9	278	2300	3000	8300	504	916
Venlafaxine	7.7	535	8474	>35000	>35000	>35000	—	—
Bupropion	9100	52600	526	6700	40000	4550	>10000	>35000
Mirtazapine	>10000	4600	>10000	0.14	794	608	69	39
Trazodone	367	>10000	>10000	220	>35000	42	35.8	224
Vortioxetine	1.6	113	—	—	—	—	—	—
Vilazodone	0.1	—	—	—	—	—	—	—
Amitriptyline (TCA)	3.1	22	5380	1.1	18	24	4.3	6.2
Nortriptyline (TCA)	16.5	4.4	3100	15	37	55	36	—
Desipramine (TCA)	17.6	0.83	3190	110	196	100	114	496

Reading the table: Ki is an inhibition constant in nM — smaller numbers = tighter binding. SERT affinity tracks SSRI potency (paroxetine/vilazodone tightest). Off-target binding predicts side effects: H1 → sedation/weight (mirtazapine 0.14, amitriptyline 1.1); mACh → anticholinergic (TCAs, paroxetine 108); α1 → orthostasis (trazodone 42, TCAs). Bupropion's only sub-µM target is DAT/NET (no SERT) — hence no serotonergic SE. Source: antidepressant Ki binding-profile table.

Antidepressant Checkpoints Pearls + Monitoring

All antidepressants carry a BBW for increased suicidal thoughts/behavior in pediatric and young adult patients (noted once here).

SSRIs

Drug	Clinical pearls	Monitoring
Citalopram	QTc prolongation. Max 40 mg (<60 yo), 20 mg (≥60 yo). Tablets + oral solution.	QTc, serum sodium, CBC
Escitalopram	Well tolerated, fewer drug interactions; QTc prolongation less likely than citalopram.	QTc, serum sodium, CBC
Fluoxetine	Long half-life (1–3 d; metabolite 4–16 d). Lots of drug interactions. Activating — dose AM.	Serum sodium, CBC; check interactions
Fluvoxamine	Only FDA-indicated for OCD. avoid with warfarin (2C9 ↑ warfarin level). Highest nausea/drowsiness/insomnia/headache.	Serum sodium, CBC
Paroxetine	Discontinuation syndrome; anticholinergic/sedating; renal & hepatic adjustments. Avoid starting if possible.	Serum sodium, CBC
Sertraline	GI side effects most prominent. safest in cardiac disease (SADHART / SADHART-CHF — safe in significant HF & post-ACS).	Serum sodium, CBC

SNRIs & others

Drug	Clinical pearls	Monitoring
Venlafaxine	Discontinuation syndrome (confirm IR vs ER); renal & hepatic adjustments; ↑BP.	BP, QTc
Duloxetine	Renal & hepatic adjustments. FDA: GAD, MDD, fibromyalgia, musculoskeletal & diabetic neuropathic pain. Smoking ↓ levels.	—
Desvenlafaxine	$$$; no proven benefit above 50 mg; renal adjustments; ER only.	SCr
Levomilnacipran / Milnacipran	Renal adjustments. Milnacipran only approved for fibromyalgia.	SCr
Bupropion	NDRI; very few sexual SE; activating (dose AM). Avoid in bulimia/anorexia & seizure history. Max 450 mg/d; smoking cessation (Zyban).	Seizure/ED history
Mirtazapine	5-HT & H₁ antagonist; sedating (greater at low dose), weight gain; good for cancer/cachexia. Does not inhibit reuptake.	LFTs, SCr, weight
Nefazodone	BBW: life-threatening hepatic failure. Less sexual SE.	LFTs
Trazodone	Mostly used for sleep (orthostasis limits antidepressant use). priapism. Sedation/dizziness common.	Priapism history
Vilazodone / Vortioxetine	SSRI + 5-HT_1A partial agonist (vilazodone). Expensive, brand-name only; no renal/hepatic adjustments.	—

TCAs & MAOIs

TCAs

amitriptyline, nortriptyline, clomipramine [OCD only], desipramine, doxepin, imipramine, protriptyline, trimipramine

QTc prolongation; smoking impacts dose; mostly hepatic metabolism.
Anti-HAM (histaminic, adrenergic, muscarinic) → sedation, orthostasis, dry/anticholinergic.
Overdose = the 3 C's: Convulsions, Coma, Cardiotoxicity (Na-channel arrhythmia).
Fall risk in elderly. Monitor: QTc, LFTs, SCr, SI risk

MAOIs

isocarboxazid, phenelzine, selegiline, tranylcypromine

DRUG + FOOD interactions; avoid tyramine-containing foods → hypertensive crisis.
Generally contraindicated in renal/hepatic impairment.
Selegiline patch: 6 mg patch exempt from food restriction; higher-dose patches watch interactions.
Washout period required when switching. Monitor: SCr, LFTs

Antipsychotics — Dosing, Receptor Thresholds & Pharmacokinetics Prescriber Reference

Receptor columns = the approximate daily dose (mg) at which that receptor becomes clinically occupied. This explains why the same drug behaves differently across its dose range (e.g., low-dose quetiapine is an antihistamine; antipsychotic D₂ occupancy needs far higher doses).

Drug	Gen	D₂ antipsychotic	H₁ sedation	M anticholinergic	α₁ orthostasis	5-HT₂A	Sedation range	Psychosis range	Mania range
Haloperidol	1st	2	—	—	—	—	1–5	5–15	10–20
Chlorpromazine	1st	100	25–50	50–100	25–50	—	25–100	200–800	400–1000
Fluphenazine	1st	2	—	—	—	—	1–2	5–20	10–20
Olanzapine	2nd	2.5	2.5–5	5–10	5–10	2.5–5	2.5–5	10–20	15–30
Risperidone	2nd	2	0.5–1	—	—	2–4	0.5–1	2–6	3–6
Quetiapine	2nd	75	25–100	300–600	150–300	100–200	25–100	150–600	300–800
Aripiprazole	2nd	10	10–15	—	—	10–15	5–10	10–30	15–30
Ziprasidone	2nd	20	30–60	—	20–40	40–80	20–40	40–80	60–80
Lurasidone	2nd	40	40–80	—	40–80	40–80	40–80	40–160	80–120

How to read it: Quetiapine occupies H₁ at 25–100 mg (pure sedation), α₁/5-HT₂A in the mid-range, but doesn't reach meaningful D₂ blockade until ~300 mg — so "50 mg for sleep" carries antihistamine/anticholinergic burden without antipsychotic benefit. Conversely haloperidol hits D₂ at 2 mg with negligible H₁/M/α₁, giving high EPS but little sedation or orthostasis. Aripiprazole is a D₂ partial agonist (functional antagonism in hyperdopaminergic states), hence akathisia rather than classic EPS.

Therapeutic plasma levels (TDM)

Evidence is strongest for clozapine; for most agents TDM is used to confirm adherence, assess rapid/poor metabolism, or investigate non-response/toxicity. Typical reference ranges (trough, ~12 h post-dose at steady state):

Drug	Reference range	Clinical use
Clozapine	≥350 ng/mL (response threshold); toxicity/seizure risk rises >600–1000	Strongest TDM evidence; check before declaring non-response; norclozapine ratio reflects adherence/metabolism
Olanzapine	20–80 ng/mL	Adherence; smokers run lower
Haloperidol	~5–17 ng/mL	Non-response/EPS; classic therapeutic window
Fluphenazine	~0.8–2.0 ng/mL	Adherence (esp. decanoate)
Perphenazine	~0.8–2.4 ng/mL	Non-response
Risperidone (active moiety)	~20–60 ng/mL (risperidone + paliperidone)	2D6 metabolizer status
Aripiprazole	~100–350 ng/mL	Adherence; long half-life (~75 h)

CYP metabolism & high-yield interactions

Drug	Primary pathway	Key interaction handle
Clozapine	CYP1A2 (major), 3A4, 2D6; UGT	Smoking induces 1A2 → levels fall (and rise ~50% on cessation — risk of toxicity). Fluvoxamine (1A2 inhibitor) can raise levels several-fold; caffeine ↑; ciprofloxacin ↑
Olanzapine	CYP1A2 + UGT (direct glucuronidation)	Smoking ↓ levels (~30% higher dose in smokers); fluvoxamine ↑
Haloperidol	CYP2D6, 3A4; also glucuronidation	Strong 2D6/3A4 inhibitors ↑ levels; inducers (carbamazepine) ↓
Risperidone	CYP2D6 → 9-OH-risperidone (= paliperidone)	2D6 inhibitors (fluoxetine, paroxetine, bupropion) ↑ parent; poor metabolizers ↑ EPS/prolactin
Paliperidone	Largely renal (minimal hepatic)	Adjust for renal function; few CYP interactions — useful in hepatic impairment
Aripiprazole / Brexpiprazole / Cariprazine	CYP2D6 + 3A4	Halve dose with strong 2D6 or 3A4 inhibitors (and in poor 2D6 metabolizers); cariprazine has very long-acting metabolites (DDCAR, weeks)
Quetiapine / Lurasidone / Iloperidone / Lumateperone	CYP3A4	Lurasidone & lumateperone contraindicated with strong 3A4 inhibitors/inducers; quetiapine levels swing with 3A4 modulators; iloperidone also 2D6
Ziprasidone	Aldehyde oxidase (~⅔) + CYP3A4 (~⅓)	Relatively interaction-light; main caution is additive QTc

Long-acting injectables (LAI)

Agent	Interval	Practical notes
Haloperidol decanoate	q4 weeks	Monthly dose ≈ 10–15× the daily oral dose; oral overlap during initiation
Fluphenazine decanoate	q2–3 weeks	Shorter interval than haloperidol
Risperidone (Consta)	q2 weeks	3-week oral overlap (no immediate release on first dose). Newer: Perseris (SC monthly), Rykindo, Uzedy
Paliperidone palmitate	Sustenna (monthly) → Trinza (q3 mo) → Hafyera (q6 mo)	Loading doses day 1 & day 8 (deltoid); no oral overlap needed; must establish on monthly before stepping to 3-/6-month
Aripiprazole	Maintena (monthly); Aristada (q4–8 wk)	14-day oral overlap (or single Aristada Initio + one oral dose)
Olanzapine pamoate (Relprevv)	q2–4 weeks	Post-injection delirium/sedation syndrome → mandatory 3-hour monitoring; REMS

Sources: user-supplied receptor/dose chart; APA Practice Guideline (2020) binding & side-effect tables; standard pharmacokinetic references. TDM ranges are commonly cited values — local lab ranges and clinical context govern. Verify before prescribing.

Antipsychotic Checkpoints Pearls + Monitoring

All antipsychotics carry a BBW for increased mortality in elderly patients with dementia-related psychosis.

First-generation (typicals)

Drug	Potency / pearls	Key monitoring
Chlorpromazine (Thorazine)	Low potency — sedation, weight gain, anticholinergic. Use lower IM doses (significant oral first-pass).	QTc (significant), orthostatic BP
Fluphenazine (Prolixin)	High potency — EPS. Available as decanoate LAI.	QTc, orthostatic BP
Haloperidol (Haldol)	High potency — EPS; CYP2D6. Decanoate LAI.	QTc significant with IV, orthostatic BP
Loxapine	High potency — EPS; inhaled form peaks in 2 min (REMS — bronchospasm).	QTc, orthostatic BP
Perphenazine (Trilafon)	Moderate potency — EPS; works in 1–3 h; CYP2D6.	QTc, orthostatic BP
Pimozide (Orap)	High potency. No schizophrenia indication; delusional disorder off-label. Get CYP2D6 genotype if >4 mg/d.	QTc significant, orthostatic BP
Thioridazine (Mellaril)	Low potency — sedation, weight gain, anticholinergic; pigmentary retinopathy.	Avoid if QTc >450
Thiothixene / Trifluoperazine	High / intermediate potency — EPS.	QTc; smoking status

Second-generation (atypicals)

Drug	Clinical pearls	Key monitoring
Aripiprazole	Highest rate of akathisia; impulse-control behaviors (gambling); LAIs (Aristada, Abilify Maintena).	A1c, BMI, akathisia
Asenapine	SL — dissolve, don't swallow; no food/drink/smoke ×10 min. Patch (Secuado).	A1c, BMI, smoking
Brexpiprazole	Akathisia. Tablets, brand only.	A1c, BMI, akathisia
Cariprazine	LONG half-life (active metabolites 7–21 d) — dose changes take weeks.	A1c, BMI
Clozapine	BBW: agranulocytosis, seizures, myocarditis/cardiomyopathy, orthostasis. Anticholinergic — bowel regimen. Smoking affects levels.	Clozapine REMS: ANC weekly to start; BMI, A1c, seizure precautions, orthostatic BP; level 200–700
Iloperidone	Dose-limiting orthostatic hypotension.	A1c, BMI
Lumateperone (Caplyta)	Only 42 mg once daily; give with food.	A1c, BMI
Lurasidone (Latuda)	Take with ≥350 cal meal; dose-related SCr increase.	A1c, BMI, SCr
Olanzapine	Metabolic SE. Relprevv LAI → post-injection delirium/sedation. Smokers may need 30% higher dose. Parenteral benzo + olanzapine → respiratory depression.	A1c, BMI
Paliperidone (Invega)	Metabolic SE; 1- & 3-month LAIs; "ghost tablet" in stool; ↑prolactin.	Prolactin, A1c, BMI
Quetiapine	Metabolic SE; ER not with food (>300 cal). Lowest D₂ block; used in Parkinson's psychosis.	QTc, A1c, BMI
Risperidone	Metabolic SE; ↑prolactin; floppy iris syndrome. LAIs Consta (IM) / Perseris (SC). Lower dose if CrCl <30 or severe hepatic.	Prolactin, A1c, BMI
Ziprasidone (Geodon)	QTc prolongation; take with ≥500 cal meal; max IM 40 mg/d.	QTc

Mood Stabilizers — Kinetics, Levels & Interactions Prescriber Reference

Drug	Half-life	Metabolism / binding	Target level	Baseline / monitoring
Lithium	~24 h	Not metabolized; renal excretion; not protein-bound	0.6–1.2 mmol/L	BUN/Cr, TSH, CBC, UA, EKG, pregnancy; Cr 1–3×/yr, TSH periodic
Valproate	6–16 h	Hepatic; >90% protein-bound	50–125 µg/mL (mania); ER 85–125	CBC/platelets, LFTs, ammonia, pregnancy. Load 20–30 mg/kg
Carbamazepine	25–65 h → 12–17 h (autoinduced)	CYP3A4; hepatic autoinduction; active 10,11-epoxide; 76% bound	4–12 µg/mL	CBC/platelets, LFTs, Na, *HLA-B1502** (Asian ancestry), pregnancy
Lamotrigine	~24 h (varies w/ inducers)	Glucuronidation (UGT)	—	Slow titration to avoid SJS; clearance ↑>50% in pregnancy
Oxcarbazepine	OXC 2 h → MHD 9 h (active)	Prodrug → MHD; no autoinduction; 40% bound	—	Na (hyponatremia ~2.5%); inhibits 2C19, induces 3A4
Topiramate	~21 h	Minimal metabolism; inhibits 2C19	—	Not effective for bipolar (4 negative RCTs); used for weight, kidney stones 1.5%
Gabapentin	5–7 h	Renal, not metabolized, not protein-bound	—	No important interactions; bioavailability ↓ at higher doses

Drugs that change lithium level

↑ Lithium (toxicity risk): thiazides, NSAIDs, ACE-inhibitors, ARBs, metronidazole; also low-sodium diet, dehydration, age, renal disease
↓ Lithium: acetazolamide, mannitol, theophylline, caffeine, aminophylline
Neutral: furosemide (loop), amiloride, aspirin

Lithium is uniquely anti-suicide — meta-analysis OR ~0.26 for suicide vs comparators across mood disorders.

Carbamazepine — the inducer trap

Autoinduces its own metabolism (level falls over 2–4 wk → re-check & re-dose)
Lowers levels of: clozapine, olanzapine, haloperidol, lamotrigine, bupropion, alprazolam, clonazepam, oral contraceptives
CBZ level raised by: fluoxetine, fluvoxamine, valproate, macrolides, cimetidine, verapamil, ketoconazole, isoniazid

Lamotrigine titration & interactions

Monotherapy: 25 mg/d ×2 wk → 50 mg/d ×2 wk → 100 → maintenance 50–400 mg
With valproate: halve the lamotrigine dose (VPA inhibits glucuronidation → doubles LTG; LTG lowers VPA ~25%)
With carbamazepine: CBZ lowers LTG ~40% → may need higher LTG
Oral contraceptives lower LTG ~49%; pregnancy ↑ clearance >50%
Rash ~10% (0.3% severe adults); predictors: fast titration, concurrent valproate, children, prior rash. Re-titrate if ≥5 missed days.

Valproate adverse profile: BBW hepatotoxicity, teratogenicity, pancreatitis; also tremor, weight gain, hair loss, thrombocytopenia/platelet dysfunction, hyperammonemia, PCOS/oligomenorrhea (~10% vs 1.4%). Displaces protein-bound drugs and inhibits glucuronidation. Avoid aspirin (↑ free VPA).

Mood Stabilizer Checkpoints Pearls + Monitoring

Drug	Pearls / BBW	Targets & monitoring
Lithium	Narrow therapeutic window; dose-related toxicity; Ebstein anomaly (contraindicated 1st trimester); nephrogenic DI, tremor, ↑PLT, acne, hypothyroidism.	Level 0.6–1.2; pregnancy test, Na, TSH, BUN/Cr
Valproate / Divalproex	BBW: hepatotoxicity, teratogenic (neural tube defects, ↓IQ), pancreatitis. Hepatic encephalopathy; thrombocytopenia/leukopenia.	Level 50–125; pregnancy test, ammonia, LFTs, CBC w/ diff
Carbamazepine	Autoinducer (renders OCPs ineffective); BBW: aplastic anemia, agranulocytosis; SJS (HLA-B*1502); hyponatremia.	Level 4–12 (for seizures); HLA-B*1502, CBC w/ diff
Oxcarbazepine	Does not autoinduce like carbamazepine. Hyponatremia.	Na, CBC, thyroid (peds)
Lamotrigine	SJS — SLOW titration (25 mg/d ×2 wk, 50 mg/d ×2 wk…). Re-titrate if >5 missed days. Not for acute hospital use.	Watch rash + fever/sore throat → d/c
Topiramate	"Topamax = Dopamax" — cognitive slowing; nephrolithiasis.	—

Lamotrigine drug interactions

With carbamazepine (↑ metabolism) → double the lamotrigine dose
With valproic acid (↓ metabolism) → halve the lamotrigine dose (combo also contraindicated per VPA note — competes for glucuronidation)
With oral contraceptives (↑ metabolism) → increase lamotrigine dose

Anxiolytics & Hypnotics — Detailed Prescriber Reference

Benzodiazepine metabolism

Glucuronidation only (safer — elderly/hepatic, no active metabolites): Lorazepam, Oxazepam, Temazepam (+ alprazolam, triazolam).

Oxidation → active metabolites (accumulate): diazepam, chlordiazepoxide, clorazepate. Nitroreduction: clonazepam.

Interaction: fluvoxamine ↑ desmethyldiazepam 100–300% (2C19)
clozapine + benzo → rare severe sedation/respiratory depression

Absorption & half-life

Drug	Onset	Half-life (h)
Diazepam	Fastest (0.5–2 h)	20–100 (≤200 elderly)
Alprazolam	Intermediate (1–2 h)	6–27 (XR 11–16)
Lorazepam	Intermediate (2 h)	10–20
Clonazepam	Intermediate (1–2 h)	30–50
Oxazepam	Slower (3 h)	5–15

Equivalence: clonazepam 0.25 ≈ lorazepam 1 ≈ diazepam 5 mg (so 3 mg clonazepam ≈ 12 mg lorazepam).

Non-benzodiazepine anxiolytics

Agent	Mechanism / dosing	Notes
Buspirone	5-HT₁A partial agonist; 5 mg bid–tid → 30–60 mg ÷; 3A4 substrate	No abuse/sedation/respiratory depression (safe in COPD); takes weeks; alcoholics need 50–60 mg
Hydroxyzine	H₁ antagonist; 10–12.5 mg bid + 25 hs	Effective for GAD (5 RCTs); no abuse/withdrawal; sedation like a benzo
Pregabalin	α₂δ Ca-channel; (Europe-approved GAD)	Largest effect size for GAD (0.5); helps sleep; expensive; not FDA-approved for GAD
Propranolol	10–40 mg 30 min before event (performance anxiety)	Half-life 3–6 h; hold if BP<90/60 or P<55; not for generalized social phobia
Prazosin	α₁ antagonist; PTSD nightmares	Titrate 1→2→4→6→10→(up to 20) mg hs (men); max 10 mg hs in women

GAD effect sizes by class: pregabalin 0.50 > hydroxyzine 0.45 > SNRIs 0.42 > benzodiazepines 0.38 > SSRIs 0.36 > buspirone 0.17. PRN benzos: useful for acute agitation (IM lorazepam 2 mg ≈ haloperidol 5 mg; combo better), but for milder anxiety they reinforce drug-seeking and undermine coping. Avoid benzos in PTSD (no effect on core symptoms, abuse risk). Start SSRI low/slow in panic; no need to in GAD/social anxiety.

Standard Medication Administration Timing Reference

University Hospitals standard administration windows (institutional reference).

Frequency-based

Schedule	Times
Daily / QAM / Weekly	9:00
QHS / Bedtime	21:00
BID	9:00, 21:00
BID with meals	8:00, 18:00
TID	0, 8:00, 16:00
TID with meals	8:00, 12:00, 18:00
QID	0, 6:00, 12:00, 18:00
Q4H	1, 5, 9, 13, 17, 21
Q6H	0, 6:00, 12:00, 18:00
Q8H	0, 8:00, 16:00
Q12H	9:00, 21:00

Medication-specific

Medication	Time
Warfarin (Coumadin)	18:00
AM insulin	6:30
PM insulin	18:00
Daily diabetic (PO)	6:30
BID diabetic (PO)	6:30, 17:00
Daily diuretic	9:00
BID diuretic	9:00, 17:00
Levothyroid	6:30
PPI daily / BID	6:30 / 6:30, 17:00
Alendronate, risedronate	6:30

Dose Equivalents & Conversions Prescriber Reference

All equivalents are approximate — derived from population averages and differ across sources. Use them as a starting point for cross-tapering, then titrate to clinical response and tolerability. (Benzodiazepine equivalents have their own detailed table above.)

Antipsychotics — chlorpromazine (CPZ) equivalents

Drug	≈ dose = CPZ 100 mg	Drug	≈ dose = CPZ 100 mg
Chlorpromazine	100 mg	Olanzapine	5 mg
Haloperidol	2 mg	Risperidone	2 mg
Fluphenazine	2 mg	Paliperidone	1.5 mg
Perphenazine	10 mg	Quetiapine	~75 mg
Trifluoperazine	5 mg	Ziprasidone	60 mg
Thioridazine	100 mg	Aripiprazole	7.5 mg
Loxapine	10 mg	Lurasidone	40 mg
Asenapine	10 mg	Iloperidone	12 mg

Caveat: CPZ equivalence is most valid for D₂-driven FGAs; for SGAs (multireceptor) it's a rough guide only. Clozapine is not converted by CPZ-equivalents — titrate independently. Newer alternatives: olanzapine-equivalents (Leucht 2016) or defined daily dose (DDD). Davis/Woods CPZ-equivalent consensus.

Antidepressants — approximate dose equivalents

Drug	≈ equivalent	Drug	≈ equivalent
Fluoxetine (reference)	20 mg	Venlafaxine	75 mg
Sertraline	50 mg	Duloxetine	30 mg
Paroxetine	20 mg	Mirtazapine	~20 mg
Citalopram	20 mg	Vortioxetine	~7 mg
Escitalopram	10 mg	Amitriptyline (TCA)	~75 mg
Fluvoxamine	~75 mg	Bupropion	~150 mg

Caveat: SSRI/SNRI "equivalence" is loose (classes differ mechanistically); use mainly to gauge whether a patient is on a low vs near-max dose, not for 1:1 swaps. Always observe washout/serotonergic-overlap rules when switching (esp. MAOIs, fluoxetine's long t½). Approximated from Hayasaka 2015 fluoxetine-equivalents.

Gabapentin ↔ Pregabalin

Conversion (≈ 6 : 1)

Gabapentin/day	≈ Pregabalin/day
300 mg	50 mg
900 mg	150 mg
1800 mg	300 mg
3600 mg (max)	600 mg (max)

Rule of thumb: gabapentin : pregabalin ≈ 6 : 1.

Why they differ (PK)

Both bind the α2δ subunit of voltage-gated Ca²⁺ channels; both renally cleared (adjust in CKD), not hepatically metabolized, no CYP interactions
Pregabalin: >90% bioavailability, linear absorption, BID; FDA: neuropathic pain, fibromyalgia, GAD (ex-US), seizures
Gabapentin: saturable absorption — bioavailability falls as dose rises (~60% at 900 → ~33% at 3600 mg), TID; off-label anxiety/alcohol/sleep
Both: sedation, dizziness, edema, weight gain; misuse potential (esp. with opioids — respiratory depression); taper to stop (rebound/seizure)

Other useful conversions

Stimulants (rough)

Methylphenidate : amphetamine ≈ 2 : 1 (MPH 10 mg ≈ amphetamine 5 mg)
Methylphenidate : dexmethylphenidate ≈ 2 : 1 (d-isomer is the active half)
Lisdexamfetamine 70 mg ≈ ~30 mg d-amphetamine (prodrug, ~30% active)
Mixed amphetamine salts ≈ dextroamphetamine ~1:1

Corticosteroids (steroid-induced neuropsych)

Equivalent glucocorticoid dose: hydrocortisone 20 = prednisone 5 = prednisolone 5 = methylprednisolone 4 = triamcinolone 4 = dexamethasone 0.75 = betamethasone 0.6 mg
Higher dose & potency → greater psychiatric risk (mania/psychosis/depression); taper to avoid adrenal crisis

Opioid MME (oral morphine equivalents) — for addiction/CL context: morphine ×1 (ref) · hydrocodone ×1 · oxycodone ×1.5 · hydromorphone ×4 · codeine ×0.15 · tramadol ×0.1 · transdermal fentanyl mcg/hr ×2.4. Methadone is non-linear and dangerous to convert (factor rises ~3→12× with dose) — never use a simple factor; buprenorphine (partial agonist) isn't part of standard MME. CDC MME factors — verify before any opioid rotation.

⚠️ Conversions are approximations for cross-tapering guidance only — verify against current prescribing information and adjust to the individual patient.

Benzodiazepine Equivalence Medication Reference

Approximate equivalents (anchored to diazepam 5–10 mg) for cross-tapering and conversion — estimates only; individualize with clinical judgment. Onset and half-life drive abuse liability and accumulation.

Drug (brand)	Approx. equiv. dose	Peak onset (h)	Half-life (incl. active metabolites)
Alprazolam (Xanax)	0.25–1 mg	0.5–1.5	6–27 h
Clonazepam (Klonopin)	0.25–1 mg	1–4	18–50 h
Lorazepam (Ativan)	1–2 mg	2–4	10–20 h
Oxazepam (Serax)	15–30 mg	2–3	5–20 h
Temazepam (Restoril)	10–30 mg	0.75–1.5	3.5–20 h
Diazepam (Valium)	5–10 mg	0.5–1	40–120 h
Chlordiazepoxide (Librium)	10–25 mg	1–4	3–120 h
Clorazepate (Tranxene)	7.5–15 mg	1–2	40–120 h
Flurazepam (Dalmane)	15–30 mg	0.5–1	47–113 h
Triazolam (Halcion)	0.25–0.5 mg	0.75–2	1.5–5.5 h

High-yield: rapid-onset short-acting agents (alprazolam, triazolam) carry the highest abuse/dependence and rebound liability; lorazepam, oxazepam, temazepam ("LOT") are glucuronidated — no oxidative metabolism, so preferred in liver disease and the elderly. For tapering, convert to a long-acting agent (diazepam or clonazepam) and reduce slowly. Source: Benzodiazepine equivalency table (Lexicomp/VA-DoD).

CYP450 Drug Interaction Reference Prescriber Reference

A medication pairing matters when one drug inhibits/induces the enzyme that metabolizes another (the substrate). >½ of patients also carry functional polymorphisms in 1A2, 2C9, 2C19, and 2D6. Compiled from the Oesterheld/Genelex substrate–inhibitor–inducer tables.

The "have-to-know" enzymes & their killer interactions

Enzyme	Must-know substrate	The interaction you can't miss
1A2	Clozapine, olanzapine	Smoking induces 1A2 → smokers need higher doses; stopping smoking (admission) ↑ levels → toxicity. Fluvoxamine (potent 1A2 inhibitor) sharply ↑ clozapine
2D6	Risperidone, aripiprazole, atomoxetine, TCAs; prodrugs: codeine, tramadol, tamoxifen	Fluoxetine / paroxetine / bupropion (strong 2D6 inhibitors) block prodrug activation → codeine/tramadol no analgesia, ↓ tamoxifen efficacy. PMs (~7%) vs ultrarapid metabolizers shift levels
2C19	(Es)citalopram, diazepam; clopidogrel (prodrug)	Fluvoxamine/omeprazole ↑ citalopram (QTc). Asian PMs ~15–20% → ↑ exposure. PPIs/2C19 inhibitors blunt clopidogrel activation
3A4	Quetiapine, lurasidone, pimozide, alprazolam/midazolam/triazolam, buspirone, methadone, statins	Ritonavir / azoles / macrolides / grapefruit (inhibitors) → ↑↑ levels; lurasidone & pimozide contraindicated with strong inhibitors. Carbamazepine autoinduces + induces others → ↓ levels/failure
2C9	Warfarin (S), phenytoin	Valproate & fluconazole inhibit → ↑ warfarin/phenytoin (bleeding, toxicity)
UGT (glucuronidation)	Lamotrigine; lorazepam/oxazepam/temazepam	Valproate inhibits → ↑↑ lamotrigine (halve the dose; SJS risk). OCPs / carbamazepine induce → ↓ lamotrigine

The high-yield inhibitor cheat-sheet: Fluvoxamine = broadest (1A2, 2C19, 3A4); Fluoxetine & Paroxetine & Bupropion & Duloxetine = the 2D6 blockers; Ritonavir / azoles / macrolides / grapefruit / nefazodone = 3A4 blockers. The big inducers: carbamazepine, rifampin, phenytoin, phenobarbital, St. John's Wort, smoking (1A2 only) — "drugs that lower the level → loss of efficacy." Sertraline, citalopram/escitalopram, and mirtazapine are the cleanest (fewest interactions).

Full substrate / inhibitor / inducer table

Enzyme	Key psychotropic substrates	Potent inhibitors	Inducers
1A2	Clozapine, olanzapine, duloxetine, tertiary TCAs, fluvoxamine, mirtazapine, ramelteon, melatonin, caffeine, theophylline	Fluvoxamine, ciprofloxacin, cimetidine, grapefruit-no	Cigarette smoke, charbroiled meat, carbamazepine, omeprazole, cruciferous veg
2D6	TCAs, fluoxetine, paroxetine, venlafaxine, atomoxetine, aripiprazole, risperidone, haloperidol; codeine/tramadol (prodrugs), metoprolol, tamoxifen (prodrug)	Paroxetine, fluoxetine, bupropion, duloxetine, quinidine, terbinafine	(none significant — genetic PM/UM status dominates)
3A4/5	Many benzos (alprazolam, midazolam, triazolam), buspirone, quetiapine, ziprasidone, aripiprazole, pimozide, carbamazepine, trazodone, zolpidem; statins, OCs	Nefazodone, ketoconazole/itraconazole, macrolides (not azithro), ritonavir, grapefruit, diltiazem, verapamil	Carbamazepine, rifampin, St John's Wort, phenytoin, phenobarbital, modafinil
2C19	Citalopram, escitalopram, diazepam, TCAs, sertraline, clopidogrel (prodrug), PPIs, phenytoin	Fluvoxamine, fluoxetine, omeprazole, modafinil, topiramate	Rifampin, St John's Wort, carbamazepine
2C9	S-warfarin, phenytoin, NSAIDs, valproate (also inhibitor), THC	Fluconazole, amiodarone, fluvoxamine, valproate, fluoxetine, sertraline (mild)	Rifampin, barbiturates, carbamazepine

The "pan-inhibitors" to memorize

Fluvoxamine — 1A2 (+ 2C19, 3A4): raises clozapine, theophylline, caffeine, TCAs, diazepam dramatically
Fluoxetine & paroxetine — strong 2D6 (long t½ for fluoxetine prolongs the effect)
Bupropion, duloxetine — 2D6
Nefazodone — strong 3A4 (avoid with pimozide, statins, many benzos)
Sertraline, citalopram, escitalopram — relatively clean (preferred with polypharmacy)

High-yield clinical consequences

Codeine & tramadol are 2D6 prodrugs → 2D6 inhibitors (paroxetine, fluoxetine, bupropion) block analgesia; ultrarapid metabolizers risk toxicity
Tamoxifen needs 2D6 activation → avoid strong 2D6 inhibitors in breast cancer
Smoking cessation ↑ clozapine/olanzapine levels (1A2 de-induction) → toxicity risk
Carbamazepine + OCPs / lamotrigine / many psychotropics → loss of efficacy
St John's Wort (3A4 inducer) → lowers many drug levels incl. antiretrovirals, OCs
Aripiprazole + strong 2D6/3A4 inhibitor → halve dose

Source: P450 Drug-Interactions Tables (J. Oesterheld, M.D. / Genelex), 2012. Illustrative — confirm specific pairings with an interaction checker before prescribing.

Pharmacogenomics & HLA Testing Prescriber Reference

CYP metabolizer phenotypes

CYP2D6 (metabolizes many antidepressants/antipsychotics; activates prodrugs): poor metabolizers (~7% White) → ↑ levels/side effects, no codeine/tramadol analgesia, ↓ tamoxifen efficacy; ultrarapid → subtherapeutic levels, codeine toxicity
CYP2C19 (citalopram/escitalopram, sertraline, TCAs, clopidogrel): poor metabolizers more common in Asian (~15–20%) populations → ↑ exposure (QTc); also blunts clopidogrel activation
Use to explain unexpected non-response/toxicity and guide dosing — not for routine first-line selection

HLA — serious cutaneous reactions

HLA-B*1502 (Han Chinese, SE Asian): carbamazepine/oxcarbazepine SJS/TEN — test before starting
HLA-A*3101: carbamazepine hypersensitivity (broader populations)
HLA-B*5701: abacavir (not psych, but classic example)

Genetic / pharmacogenomic testing — when & what

Gene	Affected drugs	Actionable guidance (CPIC)
CYP2D6	Many TCAs, fluoxetine, paroxetine, venlafaxine, risperidone, aripiprazole, atomoxetine; codeine/tramadol/tamoxifen (prodrugs)	PM: ↓ dose or alternative; UM: ↑ dose or alternative; avoid codeine/tramadol in PM (no analgesia) & UM (toxicity)
CYP2C19	(Es)citalopram, sertraline, TCAs, clopidogrel, diazepam, PPIs	PM: ↓ dose / alternative (↑ exposure, QTc); UM: consider alternative (subtherapeutic). PM blunts clopidogrel
*HLA-B1502**	Carbamazepine, oxcarbazepine, phenytoin	Test before starting in Han Chinese / SE Asian — positive → avoid (SJS/TEN)
*HLA-A3101**	Carbamazepine	↑ hypersensitivity/DRESS risk (broader ancestries) — caution/avoid
*CYP2C9 / HLA-B1502**	Phenytoin	2C9 PM → ↓ dose; HLA-B*1502 → avoid
UGT / others	Lamotrigine (glucuronidation)	No routine gene test; the clinical interaction (valproate) drives dosing

How to use it: pharmacogenomic testing is most useful to explain unexpected non-response, toxicity, or many failed trials — and is actionable pre-emptively for CYP2D6/2C19 and the HLA alleles. Get HLA-B*1502 before carbamazepine in at-risk ancestry. Caveat: commercial "combinatorial" panels (proprietary algorithms combining many genes) have weaker evidence than single gene–drug pairs — rely on CPIC/FDA gene–drug guidance, and never let a result override clinical response/tolerability. Genes are one input; adherence, interactions, and the clinical picture still govern. CPIC guidelines; FDA Table of Pharmacogenomic Biomarkers.

Lab Monitoring for Psychiatric Medications Reference Table

A "jog-your-memory" list of which agents warrant baseline and/or follow-up labs. Practice varies; this is to prompt consideration, not a substitute for product-specific guidance.

Medication / class	Recommended lab(s)
Lithium	Li level, TSH, BUN/creatinine (eGFR), calcium, pregnancy test; ECG if cardiac disease
Valproic acid	VPA level, LFTs, CBC (platelets), pregnancy test; ammonia if confusion
Carbamazepine	CBZ level, CBC, sodium, LFTs, pregnancy test; *HLA-B1502 in Asians** (SJS/TEN)
Oxcarbazepine	Sodium (hyponatremia); HLA-B*1502 in Asians
Lamotrigine	Mainly clinical (rash watch); no routine level
SGAs (esp. clozapine, olanzapine, quetiapine, paliperidone, risperidone)	Fasting glucose & lipids (metabolic monitoring); prolactin if symptomatic (risperidone/paliperidone)
Clozapine	ANC/CBC (REMS), fasting glucose & lipids; troponin/CRP if myocarditis suspected
Citalopram / TCAs / ziprasidone / thioridazine / chlorpromazine / methadone	ECG (QTc); citalopram especially if dose >40 mg/day
SSRIs	Sodium in elderly if fatigue/dizziness/confusion (SIADH)
Topiramate	Bicarbonate (metabolic acidosis)
Atomoxetine / duloxetine / disulfiram / naltrexone	LFTs if liver disease suspected
Acamprosate / amantadine / gabapentin / pregabalin	BUN/creatinine if renal impairment suspected (renally cleared)
Stimulants	ECG if cardiac disease; BP/HR
SNRIs (venlafaxine, desvenlafaxine, levomilnacipran)	Periodic BP/pulse

SGA metabolic monitoring (APA/ADA consensus)

Parameter	Baseline	Follow-up
Weight / BMI	✓	q4 wk ×12 wk, then quarterly
Waist circumference	✓	Annually
Blood pressure	✓	12 wk, then annually
Fasting glucose	✓	12 wk, then annually
Fasting lipids	✓	12 wk, then every 5 yr

Metabolic syndrome (ATP III ≥3 of): waist M ≥102 / F ≥88 cm; TG ≥150; HDL M <40 / F <50; BP ≥130/85; fasting glucose ≥100 mg/dL. Source: "Lab Monitoring for Psychiatric Medications" appendix; APA/ADA metabolic consensus.

Switching Antidepressants, Washouts & the MAOI Diet Medication Reference

Switching strategies

Direct switch (similar agents), cross-taper (taper one while starting the other — common), or taper-and-washout (required around MAOIs)
Watch discontinuation syndrome (paroxetine, venlafaxine, short t½) and serotonin syndrome from overlap
Fluoxetine's long t½ (norfluoxetine ~1–2 wk) → it self-tapers but needs a long washout before an MAOI

MAOI washouts & diet

≥2 weeks off an MAOI before starting a serotonergic drug (and vice versa); 5 weeks after fluoxetine before an MAOI
Tyramine (hypertensive) crisis: avoid aged cheeses, cured/smoked meats, fermented soy/tofu, tap/draft beer, sauerkraut, fava beans, marmite
Avoid with MAOI: SSRIs/SNRIs/TCAs, meperidine, tramadol, dextromethorphan, linezolid, sympathomimetics/decongestants, stimulants
Selegiline transdermal 6 mg patch is exempt from dietary restriction

Don't Stop Cold · Don't Restart at Home Dose Prescriber Safety

Two recurring admission hazards: (1) abruptly stopping a drug that needs a taper, and (2) resuming the home dose after a gap, when tolerance has been lost and re-titration is required. Confirm the last dose and last date taken before reordering.

Do NOT stop abruptly — taper required

Drug / class	If stopped abruptly	How to stop
Lithium	~50% mania relapse within weeks; ↑ short-term suicide risk	Taper over ≥2 wk (≈25% q2wk / 300 mg/wk)
Clozapine	Rebound psychosis, cholinergic rebound, withdrawal catatonia	Taper 1–2 wk (unless myocarditis/severe neutropenia). Catatonia → resume clozapine
Other antipsychotics	Rebound psychosis; withdrawal dyskinesia; cholinergic rebound (low-potency/anticholinergic)	Taper; cross-taper when switching
SSRIs / SNRIs (esp. paroxetine, venlafaxine; short t½)	Discontinuation syndrome — FINISH: flu-like, insomnia, nausea, imbalance, sensory "zaps", hyperarousal	Taper over weeks; fluoxetine self-tapers (long t½)
Benzodiazepines	Anxiety, insomnia, seizures, delirium (life-threatening)	Slow taper; convert to a long-acting agent
Barbiturates	Withdrawal seizures / delirium (life-threatening)	Slow taper
Gabapentin / pregabalin	Anxiety, insomnia, diaphoresis; rarely seizures	Taper over ≥1 wk
Beta-blockers (propranolol)	Rebound tachycardia/HTN, angina/MI	Taper over ~1–2 wk
Alpha-2 agonists (clonidine, guanfacine)	Rebound hypertension, agitation	Never stop clonidine abruptly — taper
Opioids (methadone, buprenorphine, full agonists)	Withdrawal (severe; dangerous in pregnancy)	Taper or continue MAT
Baclofen	Withdrawal: seizures, hyperthermia, rigidity, rhabdo (NMS-like)	Taper
Antiepileptics (VPA, CBZ, lamotrigine) in epilepsy	Breakthrough seizures / status epilepticus	Do not stop abruptly
Corticosteroids (chronic)	Adrenal crisis	Taper (medical — but common co-Rx)

Do NOT restart at the home dose after a gap — re-titrate

Drug	Gap that matters	Restart rule
Clozapine	Missed ≥48 h	≤48 h: resume. 48–72 h: 50% day 1 → 75% day 2 → 100% day 3. 72 h–1 wk: start 12.5 mg, titrate ~3 d. >1 wk: re-titrate as a new patient
Lamotrigine	Missed ≥5 days (~5 half-lives)	Restart the full titration from 25 mg — resuming maintenance risks SJS/TEN
Quetiapine / other sedating SGAs	Several days off	Re-titrate to limit orthostasis/sedation (tolerance to these is lost quickly)
LAI antipsychotics	Late/missed injection	Per-agent catch-up ± oral overlap (see LAI section)
Opioids (post-detox / incarceration / abstinence)	Days–weeks abstinent	Lost tolerance → restart LOWER (overdose-death risk at the old dose)
Benzodiazepines / barbiturates	Extended gap	Tolerance lost → restart lower to avoid oversedation

Peri-ECT corollary: hold/►reduce lithium (prolonged seizures, interictal delirium); benzodiazepines & anticonvulsants raise the seizure threshold → taper/hold before treatment; bupropion, clozapine, theophylline lower the threshold. Restart maintenance pharmacotherapy promptly after the index course (continuation is non-negotiable). ⚠️ Verify every taper/restart against current prescribing information and institutional protocol.

Tapering & Deprescribing Prescriber Reference

When the decision is to stop (not just hold). Built on the Maudsley Deprescribing Guidelines (Horowitz & Taylor 2024), Horowitz & Taylor's hyperbolic-tapering work (Lancet Psychiatry 2019), the ASAM Benzodiazepine Tapering CPG (2025), and the Ashton Manual. Most of this is consensus/expert guidance, not high-GRADE RCT evidence — individualize and go by patient response.

The hyperbolic-tapering principle

The dose → receptor-occupancy curve is hyperbolic: at high doses, big mg changes barely move occupancy; at low doses, small mg changes cause large occupancy drops
So taper by a fixed proportion (≈ equal occupancy steps), not by fixed mg — and slow down as you approach zero (the "tail" is the hard part)
Practical rule of thumb: reduce by ~5–10% of the current dose every 2–4 weeks, reassessing each step (each cut is smaller in absolute mg than the last)
The last steps often need liquid formulations or compounding ("microtapering") to reach very small doses
If withdrawal emerges: pause at the current dose (or step back up) until stable, then resume more slowly — tapers are non-linear

Withdrawal vs. relapse — the key distinction

Withdrawal = fast onset (days of a cut), includes new/physical symptoms not part of the original illness (dizziness, "brain zaps", nausea, flu-like), and resolves quickly if the dose is restored
Relapse = gradual onset over weeks–months, mirrors the original syndrome, and does not rapidly reverse with a dose increase
Rebound = transient overshoot of the original symptom (e.g., rebound insomnia/anxiety after a hypnotic) — brief, self-limited
Physical dependence ≠ addiction: nearly everyone on daily benzodiazepines >1 month becomes physically dependent; only ~1.5% develop a use disorder

Class-by-class approach

Class	Who/when	How to taper	Watch
Antidepressants (SSRI/SNRI)	Remission sustained (e.g., ≥6–12 mo for a first episode); patient preference	Hyperbolic: ~10% of current dose q2–4wk, slower near the end; worst offenders = paroxetine, venlafaxine (short t½). Fluoxetine self-tapers (long t½) and can bridge a difficult taper	FINISH discontinuation syndrome; distinguish from relapse
Benzodiazepines / Z-drugs	Risks > benefits; older adults; long-term use	ASAM: start 5–10% of total daily dose q2–4wk; faster ~25% q2–4wk if tolerated, slower ~5% q4–6wk if not. Optionally convert to a long-acting agent (diazepam — Ashton) to smooth the taper; microtaper with liquid at the tail	Seizures/delirium if abrupt; protracted withdrawal can last months. Never stop abruptly
Gabapentinoids (gabapentin, pregabalin)	Indication resolved; misuse risk	Gradual proportional reduction over ≥1–4+ weeks depending on dose/duration	Anxiety, insomnia, diaphoresis; rarely seizures
Antipsychotics	Single episode in remission; SE burden; shared decision	Slow, hyperbolic taper over months; the dopamine-occupancy curve is steep at low doses → final steps very small	Rebound/supersensitivity psychosis, withdrawal dyskinesia, cholinergic rebound
Lithium / mood stabilizers	Rarely "deprescribed" in bipolar without strong reason	If stopping, taper over weeks–months (abrupt lithium stop → ~50% mania relapse, ↑ suicide risk)	Relapse risk is high — counsel carefully

General sequence: confirm indication is truly over → shared decision & written plan → small proportional cut → monitor 2–4 wk → distinguish withdrawal vs relapse → continue, pause, or step back as needed.

Free online protocols: Horowitz & Taylor Lancet Psychiatry 2019 (hyperbolic tapering, open access) · NICE NG215 (medicines associated with dependence/withdrawal) · Royal College of Psychiatrists "Stopping antidepressants" · ASAM Benzodiazepine Tapering CPG 2025 (free PDF + pocket guides) · Ashton Manual (benzo.org.uk). The full taper tables/receptor-occupancy graphs live in the Maudsley Deprescribing Guidelines. ⚠️ Verify every regimen against current prescribing information.

Renal & Hepatic Dosing Adjustments Prescriber Reference

Renally cleared (adjust in CKD / avoid if low GFR)

Lithium (avoid CrCl <30; dose to level), gabapentin / pregabalin, paliperidone, desvenlafaxine, topiramate, amantadine, varenicline
Watch accumulation; dialysis removes lithium (and gabapentinoids)

Hepatically metabolized (caution in liver disease)

Most antidepressants/antipsychotics, valproate & carbamazepine (hepatotoxic — avoid in significant disease), benzodiazepines
Prefer LOT benzos (lorazepam, oxazepam, temazepam — glucuronidated) in liver disease/elderly
Duloxetine avoid in hepatic impairment/heavy alcohol; start low, go slow generally

Standard prescribing references — verify specific thresholds before use.

Emergencies & Safety

Agitation, toxidromes, EPS, QTc, and drug toxicities

PRNs — Agitation / Psychosis Inpatient

Typical PO (mild–moderate) and IM (moderate–severe) options with practical notes.

PO (mild–moderate)	IM (moderate–severe)	Notes
Haldol 5 mg Q6 (60 min to effect; can re-dose Q30 min)	Haldol 5 mg + Ativan 2 mg (15 min effect, calm)	Go-to if limited info. Max near 40 mg/day; ~2–5 mg for elderly.
B52 — Olanzapine/Zydis 5 mg Q6	Haldol 5–10 + Ativan 2 + Benadryl 50 mg	Severe agitation. Olanzapine: max ~30/day; avoid in high BMI & old age.
Ativan 2 mg Q6	Ativan 2 mg Q6	Used alone in PCP & meth intoxication. Watch paradoxical reaction / delirium.
Abilify 2 mg Q6 · Geodon 10–20 mg Q6	Zyprexa 5 mg or Geodon 20 mg	Geodon good for high BMI but high QT prolongation.
G52 — Thorazine 50 mg Q6	Geodon 20 + Ativan 2 + Benadryl 50	Thorazine 800 mg max; can start at 25 if worried; watch orthostatics.
Risperdal · Prolixin 5 mg Q6	Haldol or Prolixin 5 mg Q6	Prolixin good if planning decanoate LAI (IM Q2 wks) or "Haldol allergy" & dislikes Zyprexa.
Clozapine	Olanzapine 5 mg Q6	—

Caution: Do not combine parenteral olanzapine with parenteral benzodiazepines (respiratory depression — hard stop at many institutions). ⚠️ Verify all doses and institutional protocols before ordering.

EPS timing: Dystonia (min–2 days) → Benadryl 50 mg + lorazepam 2 mg. Parkinsonism (~1 wk) → benztropine. Akathisia (~1 wk). Tardive dyskinesia (years).

Acute agitation algorithm

1Verbal de-escalation first & find the cause

Reduce stimulation, offer choices; rule out reversible drivers — hypoglycemia, hypoxia, pain, delirium, intoxication/withdrawal

↓

medication needed — pick by suspected cause

2Choose by etiology

Primary psychiatric / unknown but cooperative → oral preferred: olanzapine ODT 5–10 mg, risperidone 1–2 mg, or haloperidol 5 mg
Alcohol/sedative withdrawal or stimulant/PCP intoxication → lorazepam 2 mg (benzo alone)
Delirium in the medically ill → low-dose antipsychotic, monitor QTc; avoid benzos (except withdrawal)

↓

severe / refuses PO

3IM combination

Haloperidol 5 mg + lorazepam 2 mg (± Benadryl 50 mg = "B-52"), or IM olanzapine 5–10 mg / ziprasidone 10–20 mg
Do not combine IM olanzapine + IM benzodiazepine (respiratory depression)

↓

after the acute event

4Monitor & reassess

Watch sedation/airway, EPS/dystonia (→ Benadryl + lorazepam), QTc; re-dose per interval; address the underlying cause and standing regimen

Psychiatric Emergencies First Aid

Emergency	Cause	Manifestation	Treatment
Hypertensive crisis	Tyramine-rich foods (aged cheese, cured meats, wine) + MAOI	Tyramine displaces NE → ↑ sympathetic stimulation	Phentolamine
NMS	Antipsychotics + genetic predisposition	Malignant FEVER: Myoglobinuria, Fever, Encephalopathy, Vitals unstable, ↑Enzymes (↑CK), Rigidity ("lead pipe"). Also ↑BP, ↑HR, hyper-K, ↑WBC, metabolic acidosis	Dantrolene, bromocriptine; d/c agent
Malignant hyperthermia	Inhaled anesthetics, succinylcholine + genetic predisposition	Fever, severe muscle contractions	Dantrolene
Delirium tremens	Alcohol withdrawal, 2–4 days after last drink	AMS (hallucinations), autonomic hyperactivity, anxiety, seizures, tremors, agitation, insomnia, nausea	Benzodiazepines (chlordiazepoxide, lorazepam, diazepam)
Acute dystonia	Typical antipsychotics, anticonvulsants (carbamazepine), metoclopramide	Sudden muscle spasm, stiffness, oculogyric crisis hrs–days after med; can cause laryngospasm	Benztropine or diphenhydramine
Lithium toxicity	Dose/health change (narrow window); thiazides, ACE-I, NSAIDs, nephrotoxins	Nausea, vomiting, slurred speech, hyperreflexia, seizures, ataxia, tremors, nephrogenic DI; get EKG	D/C lithium, hydrate with isotonic saline, consider hemodialysis
TCA toxicity	TCA overdose	Respiratory depression, hyperpyrexia, prolonged QT, ↓BP (orthostatic), ↑HR, dilated pupils. Tri-C's: Convulsions, Coma, Cardiotoxicity (Na-channel); get EKG	Supportive, monitor ECG, NaHCO₃ (prevents arrhythmia), activated charcoal

Carcinoid syndrome (GI/lung tumor → diarrhea, flushing, wheezing, right heart disease; tx octreotide) included for comparison with serotonin syndrome. Source: First Aid psychiatry/pathology.

NMS vs Serotonin Syndrome High Yield

Feature	Neuroleptic Malignant Syndrome	Serotonin Syndrome
Symptoms	Rigidity ("lead pipe"), fever, confusion/AMS, autonomic instability, ↑CK	Tremor, diarrhea, clonus, hyperreflexia, confusion/AMS, flushing, diaphoresis, autonomic instability
Onset	Anytime; more likely with newly introduced antipsychotic within 1–3 days	Minutes to hours
Duration	1–2 weeks (LAI: 4–6 weeks)	Hours to days
Management	ICU emergency; IVF; dantrolene; bromocriptine; ECT. Fever/rigidity respond within hours, AMS later.	Medical floor (maybe ICU); cyproheptadine 4 mg (antihistaminergic 5-HT antagonist, PO); benzos
Offending agents	Antipsychotics (1st gen > 2nd; Haldol > Thorazine); IM > IV > PO; metoclopramide, promethazine; withdrawal of parkinsonian drugs; lithium; dehydration + exertion	Linezolid (MAOI), SSRIs, bupropion, TCAs, MAOIs, triptans, diet drugs (phen-), cyclobenzaprine, trazodone, tramadol, lithium, 2nd-gen antipsychotics, ondansetron, dextromethorphan, meperidine, St. John's Wort, MDMA
Re-introduction	Re-introduce antipsychotics 2–4 wks later; use less D-blockade: clozapine < ziprasidone < quetiapine < aripiprazole < olanzapine < paliperidone < risperidone << haloperidol	—

Serotonin syndrome — "3 A's": ↑ Activity (neuromuscular: clonus, hyperreflexia, hypertonia, tremor, seizure), Autonomic stimulation (hyperthermia, diaphoresis, diarrhea), Agitation. Severe → high fever, ↑CPK, ↑WBC, ataxia, coma, death. Treat with cyproheptadine (5-HT₂ antagonist).

⚕️ Attending-level differentiation & management

Tempo & reflexes are the key discriminators: NMS evolves over days with lead-pipe rigidity and hyporeflexia; serotonin syndrome erupts over hours with clonus, hyperreflexia (lower > upper limbs), hyperactive bowel sounds, and mydriasis.
NMS labs: ↑CK (often >1000), leukocytosis, ↑LFTs, metabolic acidosis, myoglobinuria → AKI. Risk ↑ with high-potency/IM antipsychotics, rapid titration, dehydration, agitation, young males.
NMS tx ladder: stop the agent, ICU + aggressive cooling/IVF; dantrolene (rigidity/hyperthermia), bromocriptine or amantadine (dopamine agonist), benzodiazepines for milder cases; ECT if refractory. Rechallenge after ≥2 weeks with a lower-potency/lower-D₂ agent.
SS tx: stop serotonergics, supportive care, benzodiazepines; cyproheptadine 12 mg then 2 mg q2h (Hunter criteria: spontaneous/inducible/ocular clonus). Differential also includes malignant hyperthermia and anticholinergic toxicity.

Medication-Induced Toxidromes Consult-Liaison

Suspect a toxidrome in any patient on multiple psychotropics with unexplained mental-status change, abnormal movements, catatonia, or autonomic instability. Workup: timeline + full medication reconciliation (Rx/OTC/illicit), fingerstick glucose, acetaminophen/salicylate/alcohol levels, CK (rhabdo), BMP/CBC/LFTs, UDS, EKG, and head CT.

	Serotonin syndrome	NMS	Anticholinergic
Onset	Fast (minutes–hours)	Slow (days–weeks)	Fast (hours)
Cause	≥2 serotonergic agents / overdose / interaction	Dopamine blockade (or DA-agonist withdrawal)	Anticholinergic agents
Neuromuscular	Hyperreflexia, clonus (esp. lower limbs), myoclonus, tremor	"Lead-pipe" rigidity, bradyreflexia	Normal tone; myoclonus/picking
Pupils / skin	Mydriasis, diaphoresis, hyperactive bowel sounds	Diaphoresis, pallor	Mydriasis, dry/flushed skin, ↓bowel sounds, urinary retention
Labs	±↑WBC/CK/LFTs, ↓HCO₃	↑↑CK, leukocytosis, ↓Fe, metabolic acidosis	Usually normal

Serotonin syndrome

Triad: cognitive/behavioral, autonomic, neuromuscular
Hunter criteria (serotonergic agent + spontaneous clonus, or inducible/ocular clonus + agitation/diaphoresis, or tremor + hyperreflexia, or rigidity + temp >38 °C + clonus)
Culprits: SSRIs/SNRIs/TCAs/MAOIs, meperidine, fentanyl, tramadol, linezolid, dextromethorphan, triptans, ondansetron/metoclopramide, MDMA/cocaine, St. John's wort, lithium, buspirone
Mgmt: stop the agent; supportive (cool, hydrate); benzodiazepines; cyproheptadine (12 mg PO → 2 mg q2h prn; 12–32 mg/24h); usually resolves <24 h

NMS

Fever, lead-pipe rigidity, autonomic instability, Δ mental status; CK ≥4× normal
Idiosyncratic; a form of malignant catatonia
Risk: high-potency D2 blockers, DA-antagonist antiemetics (metoclopramide, prochlorperazine), dehydration, iron deficiency, IM/IV, fast titration, high dose; abrupt DA-agonist/baclofen withdrawal
Mgmt: stop neuroleptic; supportive/cooling/hydration; IV lorazepam (often 18–24 mg/day) for rigidity/catatonia; dantrolene; bromocriptine 2.5 mg BID–TID→45 mg/day or amantadine; ECT for refractory

Anticholinergic toxidrome: "mad as a hatter, red as a beet, dry as a bone, blind as a bat, hot as a hare" — delirium, mydriasis, dry flushed skin, ↓bowel sounds, urinary retention, hyperthermia. Supportive care; physostigmine in selected severe central cases. PRES (posterior reversible encephalopathy): headache, seizures, visual changes, ↑BP with vasogenic edema (parieto-occipital) on MRI — associated with immunosuppressants (tacrolimus, cyclosporine), some chemo, and severe hypertension; manage BP and remove the offending agent. Source: ACLP "How-To Guide: Medication Syndromes" (Beach & Ernst, 2020).

Extrapyramidal Symptoms (EPS) High Yield

Type	Onset	Features	Treatment
Acute dystonia	Min–2 days	Sudden sustained contraction of neck, mouth, tongue, eye (oculogyric), back; laryngospasm	Benztropine, diphenhydramine
Akathisia	~1 week	Subjective restlessness, inability to sit still, pacing	Beta-blocker (propranolol), benzodiazepine (lorazepam), benztropine
Parkinsonism	~1 week	Gradual tremor, rigidity, bradykinesia, shuffling gait, pill-rolling	Benztropine, amantadine (antiviral)
Tardive dyskinesia	Gradual, >6 mo / years	Tongue protrusion/rolling, lip smacking, chewing, facial dyskinesia, involuntary trunk/extremity movements	Valbenazine, deutetrabenazine (VMAT2 inhibitors)

Management may also include reducing dose or switching antipsychotic. Mechanism: dystonia from D₂ blockade → treat with anticholinergic (ACh blockade).

⚕️ Attending-level pearls

Akathisia is the trap — it's the most distressing EPS, raises suicide risk, and is constantly misread as agitation/anxiety/worsening psychosis. Do NOT increase the antipsychotic → reduce dose/switch; propranolol, benzodiazepine, or mirtazapine.
Acute dystonia: highest risk in young males on high-potency agents in the first days; laryngeal dystonia is an airway emergency → IM/IV diphenhydramine or benztropine; consider prophylaxis in high-risk starts.
Tardive dyskinesia: first-line is a VMAT2 inhibitor (valbenazine, deutetrabenazine); reduce/switch antipsychotic (toward clozapine or quetiapine). Anticholinergics WORSEN TD (they help acute dystonia/parkinsonism) — a classic exam trap. Monitor with AIMS.
Parkinsonism: reduce dose or switch; amantadine or benztropine. Distinguish drug-induced from idiopathic PD (symmetric, subacute onset with the drug).

QTc Prolongation Cardiac Safety

Characteristics & mechanism

QT = ventricular depolarization + repolarization, corrected for HR (QTc)
Normal QTc <460 ms (women), <450 ms (men). QTc >500 ms (or ↑ ≥60 ms from baseline) is a significant risk factor for torsades de pointes (TdP) and sudden death

Mechanism depends on the drug: TCAs prolong QT via Na & Ca channel blockade
citalopram & chlorpromazine via K-channel blockade (hERG / I_Kr). Torsades de pointes = "twisting of the points."

Measure it right: which correction formula?

RR (sec) = 60 / HR. QT & QTc in the same units.

Formula	Correction	Behavior
Bazett	QT / √RR	Default on ECG machines; over-corrects at high HR (false prolongation), under-corrects at low HR
Fridericia	QT / RR^1/3	Better at tachycardia; preferred for drug-safety monitoring
Framingham	QT + 0.154(1−RR)	Linear; performs well across rates, esp. >100
Hodges	QT + 1.75(HR−60)	Good fit across the rate range

Highest-risk agents

Typical antipsychotics: thioridazine, high-dose chlorpromazine, IV haloperidol
Atypicals: ziprasidone (greatest), iloperidone, amisulpride/sertindole (not US)
SSRIs: high-dose citalopram (>40 mg/d)
TCAs: amitriptyline, maprotiline; methadone
Non-psych: sotalol, amiodarone, quinidine; azithromycin, levofloxacin; some antifungals/antimalarials; tamoxifen

Framework — pick the formula for the patient's heart rate & rhythm:

HR ~60–100: all formulas roughly agree — Bazett is acceptable (the default)
Tachycardia (>100): avoid Bazett (over-corrects → false-positive prolongation that can wrongly stop a needed drug) → use Fridericia or Framingham
Bradycardia (<60): Bazett under-corrects (can miss true prolongation) → use Fridericia/Framingham
Atrial fibrillation / irregular: RR varies beat-to-beat → average QT over ≥5–10 beats (or report a range); avoid single-beat Bazett
Wide QRS (BBB/paced): the QT includes prolonged depolarization → use a QRS-adjusted value (e.g., JT interval) rather than raw QTc

Evidence: Fridericia & Framingham give the best rate correction and predict mortality better than Bazett, which overestimates dangerous prolongation. (AHA/JAHA 2016; CredibleMeds; ACEP toxicology.)

Measuring QTc on paper

Measure from start of QRS → end of T (where the T downslope meets the isoelectric line) — use the tangent method
Longest QT is usually in V2–V3 — measure there (or lead II)
Confirm the machine's number manually — artifact & irregular rhythm fool auto-reads
Average ≥3 beats; in atrial fibrillation, average several beats (or report a range)
Exclude U waves; quick eyeball: at normal HR the QT should be < half the RR
Normal QTc ♂ ≤450 / ♀ ≤460; borderline ~450–470; >500 = high risk

Paced rhythm & wide QRS (BBB)

Paced atrium (narrow QRS, normal conduction) → measure QTc normally
Paced ventricle / BBB (wide QRS) → the wide QRS inflates QT and overestimates TdP risk — correct it (or compare to the patient's own baseline)
Linear (wide-QRS) correction: QTc_adj = QTc − (QRS − 100)
JT interval (preferred in BBB): JT = QT − QRS; JTI = JT(HR+100)/518; JTI ≥112 = ↑ risk
Bogossian (validated in LBBB): QT_m = QT − 0.5 × QRS

"How high is too high?" — the risk-benefit framework:

QTc >500 ms → 1.66× adverse cardiac events; >550 ms → 2.14× (vs 400 ms). TdP warning signs: QTc >500, PVCs, short–long R-R sequences.
Act on absolute QTc >500 ms or an increase >60 ms from baseline.
Don't reflexively stop a high-value drug at a single number (citalopram, clozapine, methadone, IV haloperidol) — the cardiac-mortality benefit of cutting is small and the psychiatric morbidity of stopping is real.
Instead: replete K⁺ (≥4.0) and Mg²⁺ (≥2.0), remove/space other QT-prolongers, treat bradycardia, recheck at steady state.
In practice — with cardiology co-management and monitoring — clinicians often continue essential agents up to ~500 ms (selectively to ~520); >500 → add electrolyte optimization, consider adjunctive/alternative agents; risk escalates above ~550.
Monitoring: baseline + steady-state ECG for high-risk agents (thioridazine, ziprasidone, iloperidone, IV haloperidol) or multiple risk factors; cardiology consult when both.

Source: ACLP "How-To Guide: QT Prolongation" (Beach; updated 2025); Funk/Beach Am J Psychiatry 2020.

QTc-prolonging medication list

Psychotropics

Antipsychotics — highest: thioridazine, pimozide, IV haloperidol, ziprasidone, iloperidone, chlorpromazine (high dose); amisulpride, sertindole (not US)
Antipsychotics — moderate: quetiapine, olanzapine, risperidone, paliperidone, asenapine, clozapine
Antipsychotics — lower: aripiprazole, lurasidone (least)
Antidepressants: citalopram >40 mg/d (≤20 if elderly/2C19 PM/hepatic), escitalopram; TCAs (amitriptyline, maprotiline, clomipramine); trazodone
Other psychotropics: methadone (high), lithium (mild), hydroxyzine, donepezil/cholinesterase inhibitors

Other-specialty drugs (the top ~20)

Class IA antiarrhythmics: quinidine, procainamide, disopyramide
Class III antiarrhythmics: sotalol, amiodarone, dofetilide, dronedarone, ibutilide
Macrolides: erythromycin, clarithromycin, azithromycin
Fluoroquinolones: moxifloxacin, levofloxacin, ciprofloxacin
Antifungals (azoles): fluconazole, ketoconazole, voriconazole
Antimalarials / antiparasitics: chloroquine, hydroxychloroquine, halofantrine, quinine, pentamidine
Antiemetics: ondansetron, granisetron, metoclopramide
Oncology: arsenic trioxide, vandetanib, tamoxifen, nilotinib
Other: methadone, furosemide (indirect — ↓K/↓Mg), cisapride, oxytocin

⚠️ Cross-check combinations on CredibleMeds (known/possible/conditional TdP risk lists).

Risk multiplies with combinations & physiology: the danger rises when QT-prolongers are stacked or combined with metabolic inhibitors, and with hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female sex, congenital long-QT, hepatic impairment, and overdose. Correct electrolytes, minimize stacking, and get a baseline + follow-up ECG when using higher-risk agents. Check an up-to-date source (e.g., CredibleMeds) before combining QT-prolonging drugs.

Comparative QTc effect — Lancet 2013 meta-analysis (OR, lower = less risk)

Drug	QTc OR (95% CrI)
Lurasidone	−0.10 (−0.21 to 0.01)
Aripiprazole	0.01 (−0.13 to 0.15)
Paliperidone	0.05 (−0.18 to 0.26)
Haloperidol	0.11 (0.03 to 0.19)
Quetiapine	0.17 (0.06 to 0.29)
Olanzapine	0.22 (0.11 to 0.31)
Risperidone	0.25 (0.15 to 0.36)
Asenapine	0.30 (−0.04 to 0.65)
Iloperidone	0.34 (0.22 to 0.46)
Ziprasidone	0.41 (0.31 to 0.51)
Amisulpride*	0.66 (0.39 to 0.91)
Sertindole*	0.90 (0.76 to 1.02)
Clozapine / Chlorpromazine / Zotepine*	NA

*Not available in US. Higher OR = more QTc prolongation with active drug. Lippert/Leucht et al., Lancet 2013;382:951–62.

Management: identify risk factors; baseline electrolytes + ECG; cardiology consult if QTc >500 ms; for borderline QTc switch to lower-risk agent. Lower-risk antipsychotic: aripiprazole (minimal); asenapine, lurasidone, olanzapine, quetiapine also good. Lower-risk antidepressant: sertraline (most studied in cardiac patients, few interactions; avoid citalopram >40 mg).

Risk factors: congenital long QT, female sex, older age, electrolyte abnormalities (↓K, ↓Mg), hypertension; hepatic dysfunction, diabetes, hypothyroidism, AIDS; bradycardia, LV dysfunction, HF, MVP, MI; eating disorders, diuretics, hypoglycemia, renal/pituitary dysfunction. Even "low-risk" agents prolong QT in overdose.

⚕️ Attending-level pearls

Thresholds: QTc >500 ms or an increase of >60 ms from baseline is the danger zone for torsades; 450 (men)/460 (women) is the upper limit of normal.
Correct the modifiable risks first: repletion of K⁺ (>4) and Mg²⁺ (>2), avoid bradycardia, minimize combining QT-prolonging drugs; account for hepatic impairment, female sex, congenital long-QT, and diuretic/eating-disorder hypokalemia.
Don't over-restrict. The QTc is a surrogate — absolute torsades risk for most psychotropics at therapeutic doses is low. Sertraline remains preferred in cardiac patients; aripiprazole and lurasidone are the cleanest antipsychotics.
Action: baseline + follow-up ECG for high-risk agents/combinations; cardiology consult if QTc >500; switch to a lower-risk agent for borderline values.

Valproic Acid — Toxicity & Adverse Effects Special Topic

Uses & cautions

FDA uses: epilepsy, migraine prophylaxis, mania/bipolar.

Contraindications: hepatic disease, urea cycle disorders, concurrent lamotrigine (glucuronidation competition).

Formulations: Depakote (divalproex) DR (divided) / ER (once daily, slightly higher dose for equivalence; delayed-release coat, no crush/chew)
Depakene (valproic acid — avoid, GI AE)
Depakote Sprinkles (epilepsy only)

Adverse effects

Common: hair loss, weight gain, sedation, N/V/dizziness/dyspepsia, pancreatitis, GI.

Serious ("Big 3"): acute liver failure, DRESS syndrome, hyperammonemia
neural tube defects (teratogenic)

Big-3 timing: typically first month, more commonly 1–2 weeks
Watch ↑LFT, ↑ammonia, abd pain, lethargy, fever, rash, eosinophilia, ↑WBC, low platelets

Treatment of toxicity

N-acetylcysteine: 150 mg/kg/hr ×1 hr → 12.5 mg/kg/hr ×4 hr → 6.25 mg/kg/hr ×67 hr
L-carnitine (hyperammonemia): symptomatic — 100 mg/kg IV (max 6 g) over 30 min, then 15 mg/kg Q4h; asymptomatic — PO 100 mg/kg/day ÷ Q6h (max 3 g/day)
Lactulose; prednisone, famotidine, diphenhydramine (DRESS)
D/C valproate (symptoms may progress despite discontinuation); liver transplant if needed

Monitoring: baseline CBC, BMP, LFT; within 1 wk same + trough level; then 6-monthly & annually. Target VPA level 50–125.

Overdose & Toxicology Emergency

Supportive care + airway/ABCs first; decontamination (activated charcoal if early/appropriate airway); always check acetaminophen & salicylate levels in any intentional overdose.

Agent	Toxicity	Management / antidote
TCAs	"3 C's": Convulsions, Coma, Cardiotoxicity (Na-channel block — wide QRS, arrhythmia), anticholinergic, hypotension	IV sodium bicarbonate (QRS >100 ms); benzos for seizures; cardiac monitoring
Lithium	Tremor→ataxia→seizures/coma; renal failure; level may lag symptoms	IV fluids; hemodialysis (severe, level >~4, or renal failure/instability)
Acetaminophen	Hepatotoxicity (delayed)	Rumack-Matthew nomogram; N-acetylcysteine
Benzodiazepines	Sedation, respiratory depression (esp. with opioids/alcohol)	Supportive; flumazenil rarely (risk of withdrawal seizures)
Opioids	Miosis, respiratory depression, ↓consciousness	Naloxone (repeat/infusion — short t½ vs long agonists)
Anticholinergic	Hot/dry/flushed, mydriasis, delirium, retention, ↓bowel sounds	Supportive; physostigmine in select severe central cases
Salicylates	Tinnitus, tachypnea, mixed respiratory alkalosis + metabolic acidosis	Alkalinize urine (bicarbonate); dialysis if severe
Stimulants	Sympathetic storm, hyperthermia, seizures, MI	Benzodiazepines first-line; cooling; avoid β-blocker monotherapy (cocaine)

Two other psych-relevant medical emergencies: Refeeding syndrome (severe malnutrition/anorexia → on refeeding, insulin drives ↓PO₄/↓K/↓Mg, fluid shifts → arrhythmia/death; advance calories slowly + electrolytes/thiamine) and psychogenic polydipsia/water intoxication (acute hyponatremia → confusion, seizures; fluid restriction, careful correction to avoid osmotic demyelination). Standard toxicology/medical references.

Constipation — Bowel Regimen PRNs Reference Table

Constipation is common and dangerous on clozapine (ileus risk), anticholinergics, and opioids. Start a prophylactic regimen early; escalate stepwise. Senna is the drug of choice for opioid-induced constipation.

Agent	Class	Starting dose	Onset / notes
Senna (Ex-Lax)	Stimulant	1–8 tabs (8.6 mg) divided QD–BID; max 8 tabs	6–12 h; drug of choice for opioid-induced
Senna/docusate (Senna-S)	Stimulant + softener	1–2 tabs QD–BID	Combo; common standing order
Bisacodyl (Dulcolax)	Stimulant	1–8 tabs PO; or 1 suppository PR	Tab 6–10 h; suppository 15 min–2 h
Polyethylene glycol (Miralax)	Osmotic	17 g in 8 oz fluid daily; max 34 g	24–96 h; best-tolerated; preferred in renal impairment
Lactulose	Osmotic	15–30 mL QD; max 240 mL	24–48 h; laxative of choice in liver failure (titrate to 3–4 soft stools); no glucose rise
Magnesium hydroxide (MOM) / Mg citrate	Osmotic	MOM 30–60 mL; Mg citrate ½–1 bottle	30 min–6 h; contraindicated in renal impairment; avoid in heart failure (salt)
Glycerin suppository / sodium phosphate enema	Rectal	1 suppository or 1 enema PR PRN	Enema 2–15 min; rescue for hard, distal stool

Stepwise approach: softener + stimulant (senna-docusate) standing → add an osmotic (PEG) → rectal measures (suppository/enema) for impaction. On clozapine, ask about bowel function at every visit — silent constipation can progress to ileus, obstruction, and death. Source: Constipation PRN reference (OnePoint).

Disorders & Clinical Topics

Diagnostic families, clinical pearls, psychotherapy & neuromodulation

Chapter 5 vs Chapter 2: This chapter is clinical knowledge by syndrome (criteria, pearls, non-pharmacologic care). For step-by-step medication algorithms, see Chapter 2 — Treatment Algorithms.

Neurodevelopmental & Disruptive

Schizophrenia, Mood & Related

Anxiety, OCD, Trauma & Somatic

Personality, Eating, Sleep & Sexual

Neuropsychiatry & Special Topics

Treatments & Neuromodulation

Neurodevelopmental Disorders Clinical Topic

Onset in the developmental period; deficits in personal, social, academic, or occupational functioning. (ADHD has its own section.)

Disorder	Core features	Management
Autism spectrum disorder	Persistent deficits in social communication + restricted/repetitive behaviors/interests; sensory sensitivities; early onset	Behavioral (ABA/early intervention); risperidone/aripiprazole FDA-approved for irritability/aggression; SSRIs for comorbid anxiety/OCD
Intellectual disability	Deficits in intellectual + adaptive functioning (conceptual/social/practical); severity by adaptive function	Supports/education; treat comorbid psychiatric illness; avoid diagnostic overshadowing
Tourette / tic disorders	Motor + vocal tics >1 yr (Tourette); wax/wane, premonitory urge; high OCD/ADHD comorbidity	CBIT (habit reversal) first-line; alpha-2 agonists (guanfacine/clonidine); antipsychotics/VMAT2 if severe
Communication / learning	Specific learning (reading/math/writing), language, speech-sound disorders	Educational accommodation

DSM-5-TR; AACAP practice parameters.

Adult ADHD Clinical Topic

~4.4% of US adults; 50–60% of childhood ADHD persists into adulthood (the "symptoms always remit" idea is a myth). Highly heritable (~80%). Not a deficit of attention but an impairment of executive function — regulating attention and impulsivity. Pathophysiology: under-active prefrontal cortex, anterior cingulate, striatum, cerebellum; dopamine + norepinephrine dysregulation.

DSM-5 diagnosis

3 presentations: combined, predominantly inattentive, predominantly hyperactive-impulsive
≥5 symptoms (adults ≥17 yo) vs ≥6 (youth), inattentive and/or hyperactive-impulsive
Several symptoms before age 12; impairment in ≥2 domains (now includes work)
Clinical diagnosis — no confirmatory test; collateral required; rating scales (CAARS, WRAADDS, ASRS)
Rule out mimics: thyroid, sleep disorders, substance use, tics; screen cardiac history

Comorbidity is the rule: ~35% mood, ~47% anxiety; ~87% have ≥1 comorbidity. Treat the most impairing illness first.

Medication overview

First-line: stimulants (70–85% response) and atomoxetine
Stimulant MOA: methylphenidate blocks reuptake; amphetamine also releases NT from vesicles
Amphetamine → more sleep/appetite effects than methylphenidate
2nd-line: bupropion, TCAs; α₂-agonists (clonidine/guanfacine — good for impulsivity, tics, comes long-acting)
Modafinil "probable"; SSRIs ineffective for ADHD (treat comorbid mood/anxiety)

Cardiac BBW: document personal & family history (murmur, syncope, exercise intolerance, HTN, structural defect, sudden death) before stimulants.

Formulations & adult dosing

Long-acting agent	IR : delayed	Note
Concerta (MPH)	22% : 78% (osmotic)	—
Metadate CD (MPH)	30% : 70% (beads)	—
Ritalin LA (MPH)	50% : 50% (beads)	—
Focalin XR (d-MPH)	50% : 50%	d-isomer only active → use ½ the usual MPH dose
Adderall XR (mixed AMPH salts)	50% : 50%	—

Adult maxima (often exceed pediatric): amphetamine 60–80 mg (lisdexamfetamine 70 mg), methylphenidate 80–100 mg, atomoxetine 120 mg. Atomoxetine: selective NRI → ↑DA in PFC but not striatum (less tic risk); CYP2D6 substrate (caution with paroxetine/fluoxetine); no abuse potential; allow 6–8 weeks for full effect; BBW suicidal thinking. Diversion is rare when diagnosis is reliable.

⚕️ Attending-level pearls

Stimulants have the largest effect size in psychiatry (~0.9). Methylphenidate vs amphetamine response is idiosyncratic — try both before calling a patient a non-responder.
Prefer long-acting formulations (adherence, smoother coverage, lower diversion/misuse). Non-stimulants: atomoxetine/viloxazine, α₂-agonists (guanfacine/clonidine ER); bupropion off-label.
Cardiac history before stimulants (sudden death, structural disease); monitor BP/HR and (in children) growth.
Comorbidity is the rule — treat the most impairing condition first. Stimulants are generally safe with controlled comorbid anxiety or stabilized substance use disorder.

Schizophrenia-Spectrum & Other Psychotic Disorders Clinical Topic

Defined largely by duration and the presence/absence of a mood component. (Schizophrenia treatment has its own algorithm.)

Disorder	Duration / defining feature
Brief psychotic disorder	Psychosis ≥1 day to <1 month, full return to baseline; often post-stressor/postpartum
Schizophreniform	Schizophrenia symptoms 1–6 months (functional decline not required)
Schizophrenia	≥6 months (incl. ≥1 mo active phase) + functional decline
Schizoaffective	Concurrent mood episode + schizophrenia criteria, but ≥2 wk of psychosis WITHOUT prominent mood symptoms (this distinguishes it from a mood disorder with psychotic features)
Delusional disorder	≥1 month of delusions, function otherwise preserved, no other active psychotic symptoms (erotomanic, grandiose, jealous, persecutory, somatic)
Shared psychotic / substance- or medical-induced	Folie à deux; or attributable to a substance or medical condition

Key discriminators: mood-congruent psychosis only during mood episodes → mood disorder with psychotic features; psychosis persisting ≥2 wk without mood symptoms → schizoaffective. Always exclude substance/medical causes (see Medical Mimics). DSM-5-TR.

Atypical Depression Clinical Topic

More common than melancholia; typically early-onset and chronic, familial, and lacks melancholia's biological abnormalities (normal sleep architecture, DST, tyramine). Historically defined (West & Dally 1959) as TCA-unresponsive but MAOI-responsive.

DSM criteria

Major depression/dysthymia + mood reactivity + ≥2 of:

Hyperphagia / weight gain
Hypersomnia
Leaden paralysis
Rejection sensitivity (long-standing trait)

Does not meet criteria for melancholic or catatonic features.

Treatment

MAOIs classically superior: phenelzine 71% > imipramine 50% > placebo 28% (Liebowitz 1988)
SSRIs also effective and now first-line in practice: fluoxetine 51% ≈ imipramine 53% > placebo 23% (McGrath 2000)
Moclobemide (RIMA) — not US-available
TCAs relatively less effective than in melancholia

Patients least like melancholia (early onset, never-well) respond best to MAOI over TCA.

⚕️ Attending-level pearls

The historical signal: MAOIs (phenelzine) outperformed TCAs for atypical features (Columbia: phenelzine 71% > imipramine 50% > placebo) — SSRIs are now first-line for tolerability.
Bupropion fits the phenotype — activating and weight-neutral, helpful given the hypersomnia and hyperphagia.
Always re-examine for bipolar II — atypical features (mood reactivity, rejection sensitivity, hypersomnia) overlap heavily and change the treatment.
Leaden paralysis and rejection sensitivity are the most specific features; early onset + chronic course is typical.

Treatment-Resistant Depression Clinical Topic

~20% of MDD becomes treatment-resistant. ~15% of TRD patients die by suicide. Cumulative remission across the four STAR*D steps is only ~⅔, and each successive step has lower remission and higher relapse.

Thase–Rush staging

Stage 1: failure of 1 adequate trial
Stage 2: failure of 2 trials of different classes
Stage 3: stage 2 + failed augmentation
Stage 4: stage 3 + failed 2nd augmentation
Stage 5: stage 4 + failed ECT

STAR*D remission by level

L1 citalopram 28%; L2 switch 18–25% / augment ~30%; L3 12–25%; L4 7–14%
Switch ≈ augment; cognitive therapy ≈ medication
Relapse of remitters climbs each step: 40 → 55 → 65 → 71%
2/3 of citalopram responders improved by week 6

Rule out pseudo-resistance first: misdiagnosis (esp. bipolar), inadequate dose/duration (need 6–12 wk), nonadherence (≥50% of patients), occult substance use, occult medical (thyroid/adrenal axes), nutritional deficiency (folate, B12, B6, thiamine), comorbid anxiety/personality disorder. Predictors: high baseline severity, early onset, comorbid anxiety/substance, childhood abuse, low social support.

Neuromodulation devices

Device	Notes
ECT	Most effective; see ECT section. Greater resistance → lower response & higher post-ECT relapse
TMS	Effect size less than ECT; noninvasive; modest–moderate vs sham
VNS	Non-acute — effects take 16–24+ weeks; surgical; MRI-incompatible
DBS	Investigational for TRD (subgenual cingulate Cg25); FDA-approved for Parkinson's/tremor/OCD

⚕️ Attending-level evidence & pearls

Exclude pseudo-resistance first (the most common reason a case looks refractory): missed bipolar diagnosis (screen with MDQ), subtherapeutic dose/duration, nonadherence (~50%), occult substance use, and medical contributors (hypothyroidism, sleep apnea, anemia, B12).
Augment vs switch: augment if there's a partial response, switch if none/intolerable. FDA-approved adjuncts: aripiprazole, brexpiprazole, quetiapine XR, cariprazine; lithium and T3 are cheap, effective (level A).
Esketamine (intranasal, REMS, given with an oral antidepressant) is FDA-approved for TRD; IV ketamine off-label has a rapid anti-suicidal effect (transient).
Device ladder: ECT remains most effective; rTMS for moderate resistance; VNS for chronic resistance. Trial an MAOI before declaring true resistance.

OCD-Related & Impulse-Control Disorders Clinical Topic

Obsessive-compulsive related

Hoarding disorder: persistent difficulty discarding; clutter impairs use of space; poor insight common — CBT (specialized); SSRIs modest
Trichotillomania (hair-pulling) & excoriation (skin-picking): recurrent body-focused behavior; habit-reversal training first-line; NAC/SSRI variable
Body dysmorphic disorder — see its own section (high-dose SSRI + CBT)

Impulse-control & behavioral addiction

Intermittent explosive disorder: recurrent aggression out of proportion to provocation; SSRIs + CBT (anger management)
Gambling disorder (the DSM-5 behavioral addiction): chasing losses, tolerance, withdrawal-like; CBT/GA; naltrexone shows benefit
Kleptomania (stealing for the urge, not value), pyromania — rare; psychotherapy; treat comorbidity

Body Dysmorphic Disorder Clinical Topic

Common (~1.7–2.4% community; higher in derm/cosmetic-surgery settings) yet markedly underdiagnosed. Onset ~age 16 (≈⅔ before 18). Preoccupations consume 3–8 h/day.

Diagnosis

Preoccupation with a perceived defect that is not observable or appears slight to others + repetitive behaviors (mirror checking, grooming, skin picking, reassurance-seeking, comparing)
Causes significant distress/impairment
not better explained by an eating disorder

Insight specifier: good/fair → poor → absent/delusional (~35%)
Muscle dysmorphia subtype
BDD-related delusions of reference common

Suicidality (very high)

Lifetime suicidal ideation ~80%
Suicide attempts 24–28%
Completed suicide markedly elevated — possibly > MDD and bipolar
Psychiatric hospitalization 38%

Treatment: SRIs are first-line — including for delusional BDD (antipsychotic monotherapy is not preferred; SRIs treat the delusional form). Use high doses, like OCD. Clomipramine > desipramine (SRI > non-SRI); fluoxetine > placebo. CBT tailored to BDD (exposure, ritual prevention, perceptual retraining) is best-supported psychotherapy. Cosmetic/surgical treatment is rarely effective and should be discouraged. No medication is FDA-approved for BDD.

⚕️ Attending-level pearls

SRIs are first-line even for delusional BDD — treat it like OCD, not psychosis; an antipsychotic alone is the wrong move. Use high doses and long trials (12–16 wk); clomipramine > desipramine.
Augment partial responders with an antipsychotic; BDD-specific CBT (with perceptual retraining) is the core psychotherapy.
Extremely high suicidality (SI ~80%, attempts 24–28%) — screen aggressively and monitor.
Cosmetic/surgical procedures rarely help and often worsen the disorder — actively discourage them.

Dissociative Disorders Clinical Topic

A disruption of the normal integration of consciousness, memory, identity, emotion, perception, or behavior — strongly associated with severe/repetitive childhood trauma.

DSM-5-TR disorders

Dissociative identity disorder (DID): ≥2 distinct personality states + recurrent gaps in recall; marked distress/impairment; not normal cultural/religious practice
Dissociative amnesia: inability to recall important (usually traumatic) autobiographical info, beyond ordinary forgetting; ±dissociative fugue (purposeful travel/wandering with amnesia)
Depersonalization/derealization disorder: persistent/recurrent detachment from self (depersonalization) or surroundings (derealization) with intact reality testing

Workup & treatment

Rule out seizures (esp. temporal lobe), substance/medication, TBI, malingering/factitious; screen with DES-II
Psychotherapy is primary — trauma-focused, phase-oriented (safety/stabilization → processing → integration); avoid abrupt "memory recovery"
No FDA-approved medication; treat comorbid PTSD/depression/anxiety; SSRIs may help depersonalization symptoms modestly
High comorbidity: PTSD, depression, borderline PD, self-harm/suicidality

Somatic Symptom & Related Disorders Clinical Topic

Distress and dysfunction centered on physical symptoms or health — with positive psychological features, not merely "medically unexplained." (Functional neurological disorder is the C-L workhorse here.)

Disorder	Core feature	Key point
Somatic symptom disorder	≥1 distressing somatic symptom + excessive thoughts/feelings/behaviors about it, ≥6 mo	Symptom may or may not be medically explained; it's the response that defines it
Illness anxiety disorder	Preoccupation with having/acquiring serious illness with minimal/no somatic symptoms	Care-seeking or care-avoidant type (formerly "hypochondriasis")
Functional neurological (conversion)	Neurologic symptoms (weakness, nonepileptic seizures, sensory) incompatible with disease	Positive signs (Hoover sign, tremor entrainment); dx is rule-in, not exclusion
Factitious disorder	Deliberate falsification of illness without external incentive (motive = sick role)	Imposed on self or another (formerly Munchausen / by proxy = abuse)
Malingering (not a disorder)	Feigning for external gain (money, drugs, avoiding work/law)	A V-code; consider with legal/financial context, poor cooperation

Somatic Symptom Disorder — diagnose & treat

How to diagnose (DSM-5-TR):

(A) ≥1 distressing somatic symptom disrupting daily life
(B) Excessive thoughts/feelings/behaviors about it — ≥1 of: disproportionate persistent thoughts about seriousness; persistently high health anxiety; excessive time/energy devoted to symptoms/health
(C) Persistent — typically >6 months (any one symptom may change)
Specify: predominant pain; persistent; mild/moderate/severe. The symptom may be medically explained — it's the response that defines it

Treatment/therapy: single trusted PCP, regular scheduled visits (not symptom-driven); CBT (first-line evidence); treat comorbid depression/anxiety with SSRIs/SNRIs; mindfulness; avoid unnecessary tests/specialists

Illness Anxiety Disorder — diagnose & treat

How to diagnose (DSM-5-TR):

Preoccupation with having or acquiring a serious illness
Somatic symptoms are absent or mild (if a real condition exists, the worry is clearly excessive)
High health anxiety; alarmed easily about health
Excessive health behaviors (checking, seeking reassurance) or maladaptive avoidance (of doctors/hospitals)
Present ≥6 months; specify care-seeking vs care-avoidant (formerly "hypochondriasis")

Treatment/therapy: CBT (first-line — reduce checking/reassurance-seeking, cognitive restructuring); SSRIs effective; scheduled visits with one clinician; limit unnecessary testing

Functional Neurological (Conversion) Disorder — diagnose & treat

How to diagnose (DSM-5-TR):

≥1 symptom of altered voluntary motor or sensory function (weakness, nonepileptic seizures, tremor, gait, sensory loss, aphonia)
Positive evidence of incompatibility with recognized neurologic disease — a rule-in diagnosis, not exclusion: Hoover sign (hip-extension weakness resolves with contralateral flexion), tremor entrainment, give-way weakness, normal video-EEG during a "seizure"
Not better explained by another disorder; causes distress/impairment
"La belle indifférence" is not diagnostic. Acute stressor common but not required

Treatment/therapy: explain the diagnosis positively ("the wiring/software, not damage; it's reversible"); physiotherapy (motor/gait), CBT, treat comorbid depression/anxiety/PTSD; multidisciplinary; avoid reinforcing the sick role

Factitious Disorder (incl. Munchausen) — diagnose & treat

How to diagnose (DSM-5-TR):

Falsification of physical/psychological signs or symptoms, or induction of injury/disease, associated with identified deception
Presents self (or another) to others as ill/impaired
No obvious external reward — the motivation is to occupy the sick role (distinguishes from malingering)
Imposed on self ("Munchausen" = severe, chronic, with travel/many hospitals) vs imposed on another (formerly "by proxy" — a form of child/elder abuse; perpetrator gets the diagnosis, victim is coded as abuse → mandated reporting & child protection)
Clues: dramatic/inconsistent history, eagerness for invasive tests, illness that worsens before discharge, medical sophistication

Treatment/therapy: no specific drug; non-punitive, face-saving confrontation; minimize iatrogenic harm; treat comorbid depression/personality disorder; imposed on another → ensure victim safety + report. Engagement is difficult (patients often leave)

Malingering — not a mental disorder

How to identify: intentional feigning/exaggeration for an external incentive (money, disability, drugs, avoiding work/military/legal consequences). A V/Z-code, not a diagnosis
Suspect with: medicolegal context, marked discrepancy between claimed distress and objective findings, poor cooperation with evaluation/treatment, antisocial traits
Management: objective documentation, avoid colluding or confronting aggressively, validated effort/symptom-validity testing where appropriate; not "treated" psychiatrically

Cross-cutting management: a single trusted clinician, regular scheduled visits (not symptom-contingent), validate distress, minimize unnecessary tests/procedures, treat comorbid depression/anxiety, and use CBT (and physiotherapy for FND). Telling a patient "it's all in your head" backfires. Key motive contrast: SSD/IAD/FND = not intentional; factitious = intentional, motive is the sick role; malingering = intentional, motive is external gain. DSM-5-TR; C-L psychiatry references.

Grief, Bereavement & Adjustment Clinical Topic

Normal grief vs depression

Grief: waves of sadness tied to the loss, preserved self-esteem, able to experience positive emotion; yearning predominates
Major depression: pervasive low mood/anhedonia, worthlessness/guilt, global; can be precipitated by loss
They can coexist — diagnose MDD if criteria met

Prolonged grief & adjustment

Prolonged grief disorder (DSM-5-TR): intense yearning/preoccupation + emotional pain persisting >12 months (adults) with functional impairment
Adjustment disorder: emotional/behavioral symptoms within 3 months of an identifiable stressor, resolving within 6 months of its end (with anxiety, depressed mood, conduct, mixed)
Treatment: psychotherapy (grief-focused CBT/complicated-grief therapy); treat comorbid MDD/PTSD

Personality Disorders — Pharmacotherapy Clinical Topic

Psychotherapy is the mainstay (DBT, MBT, TFP, schema, STEPPS for borderline). Medication targets symptom dimensions, not the disorder itself. Best-studied: schizotypal, borderline, avoidant.

General principles

Treat any comorbid major disorder (MDD, bipolar, panic) and substance use disorder first — mood lability/impulsivity may remit
Start low, go slow — half the dose and half the titration rate you'd use for a major disorder (sensitivity to side effects)
Operationalize & track target symptoms; mind overdose potential and abuse potential
Avoid benzodiazepines — disinhibition, acting-out, depression

Target dimension	Agents
Cognitive-perceptual (schizotypal: ideas of reference, transient psychosis)	Low-dose atypical antipsychotic — risperidone ~1–2 mg (start ≤1 mg)
Affective instability (borderline — the sine qua non)	SSRIs; mood stabilizers (lamotrigine, valproate, topiramate, lithium); low-dose atypicals (aripiprazole broad benefit, quetiapine); omega-3 FA
Impulsivity / aggression	SSRIs (serotonin most implicated), lithium, anticonvulsants. Avoid amphetamine/stimulants (worsen impulsivity)
Anxious cluster (avoidant — a chronic, pervasive social phobia)	SSRIs, MAOIs (1 yr → 70% no longer met avoidant criteria); beta-blockers less effective; benzos only temporary

Borderline PD is highly heritable (~69%) with serotonergic dysfunction in the impulsive-aggression trait and reduced/under-activated frontal-OFC regions. Watch antipsychotic weight gain (these patients are often already overweight).

⚕️ Attending-level pearls

No drug is FDA-approved for any personality disorder — medications target symptom domains, and psychotherapy (DBT for borderline) is primary.
Borderline PD: SSRIs for affective/impulsive symptoms; mood stabilizers (lamotrigine, topiramate, valproate) for impulsivity/aggression; low-dose SGA (aripiprazole, quetiapine) for cognitive-perceptual/anger; omega-3 adjunct.
Avoid benzodiazepines (disinhibition, dependence) and minimize polypharmacy; mind overdose risk in impulsive patients (limit quantities).
Schizotypal PD: low-dose antipsychotic (e.g., risperidone) for cognitive-perceptual distortions. Treat comorbid mood/anxiety/substance disorders, which often drive the presentation.

Eating Disorders — Pharmacotherapy Clinical Topic

Anorexia Nervosa

No medication of proven benefit for underweight patients or relapse prevention
SSRIs ineffective while underweight (malnutrition may blunt drug action) and didn't prevent relapse with CBT (Walsh 2006)
Olanzapine — intriguing signal for weight gain; more data needed
Best treatment: calories + psychotherapy

Bulimia Nervosa

Fluoxetine 60 mg/d — the only FDA-approved drug (20 mg is NOT effective); rapid response
Most antidepressant classes reduce bingeing/purging
CBT first-line (≥ medication); combine modestly helpful
Experimental: topiramate, ondansetron

Binge Eating Disorder

Lisdexamfetamine — only FDA-approved (↓ binges + weight); caution: CV effects, abuse, no >12-wk data
Antidepressants (SSRIs) reduce binge frequency
Topiramate, zonisamide also studied
Psychotherapy (CBT) effective; older/more often male, usually obese

DSM-5-TR feeding & eating diagnoses

Disorder	Core features
Anorexia nervosa	Restriction → significantly low weight; intense fear of weight gain; body-image disturbance. Subtypes: restricting vs binge-purge
Bulimia nervosa	Binge + compensatory behavior (purging/exercise/fasting) ≥1×/wk for 3 mo; usually normal weight
Binge-eating disorder	Binges without compensation, ≥1×/wk for 3 mo; distress, no purging
ARFID	Avoidant/restrictive intake (low interest, sensory aversion, fear of aversive consequences) → weight loss/nutritional deficiency/feeding dependence — without body-image disturbance
Pica	Eating non-nutritive non-food substances ≥1 mo, developmentally inappropriate
Rumination	Repeated regurgitation/re-chewing of food, not due to a GI/medical cause

Refeeding syndrome: in severe malnutrition, reintroducing carbohydrate → insulin surge → intracellular shift of phosphate, potassium, magnesium + thiamine depletion → arrhythmia, heart failure, seizures, death. "Start low, go slow" (~10–20 kcal/kg/day), check & replete electrolytes/phosphate, give thiamine, monitor cardiac. Highest risk: BMI <16, minimal intake >10 days, low baseline electrolytes.

⚕️ Attending-level pearls

Anorexia: no drug improves weight or core symptoms (olanzapine has only a modest weight signal); SSRIs don't work while underweight or prevent relapse. Nutrition + psychotherapy (FBT in adolescents) is the treatment.
Watch the medical emergencies: refeeding syndrome (↓phosphate/K/Mg — refeed slowly, replete phosphate), bradycardia, prolonged QTc, hypoglycemia. Bupropion is contraindicated (seizure risk).
Bulimia: fluoxetine 60 mg is the only FDA-approved drug; CBT is first-line. BED: lisdexamfetamine (FDA-approved), plus SSRIs/topiramate; CBT.
Avoid stimulants/diuretics/insulin manipulation cues; comorbid depression/anxiety/OCD are common and treatable.

Sleep Disorders Clinical Topic

Sleep disturbance independently raises suicide risk (RR ~2–3) even without a mood disorder. Insomnia is driven by conditioned hyperarousal (predisposing → precipitating → perpetuating).

Chronic insomnia — treatment

CBT-I is first-line (ACP 2016) for all adults. NIH State-of-the-Science: only CBT-I and benzodiazepine-receptor agonists have evidence; antipsychotics, antidepressants, and trazodone are not recommended for chronic insomnia (risk > benefit). Sleep hygiene alone is usually ineffective. CBT-I components: stimulus control, sleep restriction, paradoxical intention.

Hypnotic	Dose	Half-life	Class / note
Zolpidem (Ambien) / ER	5–10 / 6.25–12.5 mg	~2–3 h	Z-drug; sleep onset (ER also maintenance); SL 1.75 mg ♀/3.5 ♂
Zaleplon (Sonata)	5–10 mg	~1 h	Z-drug; ultra-short, middle-of-night use
Eszopiclone (Lunesta)	1–3 mg	5–7 h	Z-drug; onset + maintenance
Temazepam (Restoril)	7.5–30 mg	8–20 h	Benzodiazepine
Triazolam (Halcion)	0.125–0.25 mg	2–4 h	Benzodiazepine; short
Ramelteon (Rozerem)	8 mg	1–2.6 h	Melatonin MT1/MT2 agonist; sleep onset; no abuse/GABA
Doxepin (Silenor)	3–6 mg	~17 h	H₁ antagonist; sleep maintenance; not scheduled
Suvorexant (Belsomra)	10–20 mg	~12 h	Dual orexin antagonist; Schedule IV; narcolepsy-like SE

Avoid long half-life hypnotics (flurazepam, quazepam) — daytime sedation, falls, confusion, esp. elderly. OTC antihistamines (diphenhydramine, doxylamine): anticholinergic burden (delirium, retention, glaucoma).

OSA · RLS

OSA: independent cardiovascular/HTN risk (sympathetic surge, intermittent hypoxia); occurs at any BMI; CPAP first-line (also oral appliances, weight loss, positional, surgery)
RLS (4 criteria — Urge to move + worse at rest, relieved by movement, worse in evening): dopaminergics, gabapentinoids, opioids, benzos; check ferritin/iron → oral iron + vitamin C

Narcolepsy · Parasomnias

Narcolepsy: loss of hypothalamic hypocretin/orexin neurons (autoimmune; H1N1/Pandemrix link); cataplexy pathognomonic; sleep-onset REM. Tx: scheduled naps + stimulants/modafinil; anticataplexy = GHB (sodium oxybate), SSRIs/venlafaxine, TCAs.
Parasomnias: NREM arousal disorders (sleepwalking, terrors) vs REM behavior disorder; both can cause sleep-related violence
Safety + clonazepam 0.5–2 mg

⚕️ Attending-level pearls

CBT-I is first-line for chronic insomnia — durable and side-effect-free; pharmacotherapy is adjunctive and ideally short-term.
Avoid chronic benzodiazepines and Z-drugs (tolerance, falls, dependence; FDA boxed warning for Z-drug complex sleep behaviors). Prefer low-dose doxepin, ramelteon, or a DORA (suvorexant/lemborexant) for maintenance; melatonin for circadian misalignment.
Trazodone is widely used off-label but has limited insomnia evidence (orthostasis, priapism); antipsychotics should not be used for primary insomnia (metabolic risk, Beers).
Treat the comorbidity: OSA → CPAP (sedatives worsen it); RLS → dopaminergics/gabapentinoids + check ferritin; depression-with-insomnia → a sedating antidepressant rather than a separate hypnotic.

Sexual Dysfunction Clinical Topic

Sexual function = a dynamic balance of excitation (dopamine, norepinephrine, melanocortin, oxytocin, testosterone) vs inhibition (serotonin, opioids, prolactin, endocannabinoid) — the "sexual tipping point." Response models: Masters & Johnson (linear), Kaplan (adds desire), Basson (circular — better fit for many women).

Prevalence & the depression link

Women (PRESIDE, with distress): any 12%; desire 10%, arousal 5.4%, orgasm 4.7%
Men: ED ~30%, premature ejaculation ~30%, low interest ~14%
Bidirectional: depression → +50–70% SD risk; SD → +130–210% MDD risk
SD can be a symptom of depression itself, the medication, the comorbidity, or the relationship

Contributors: anything lowering testosterone (hyperprolactinemia, opiates, menopause), beta-blockers, diuretics, OCPs, antipsychotics, diabetes, thyroid.

Antidepressant SD (Serretti meta-analysis)

Highest rates: SSRIs (paroxetine, sertraline, citalopram, fluoxetine), venlafaxine, TCAs, oral MAOIs.

Lowest / favorable: bupropion, mirtazapine, nefazodone, agomelatine, vilazodone, vortioxetine, selegiline transdermal, desvenlafaxine, duloxetine (relatively).

Managing SSRI-induced sexual dysfunction

Maximize treatment of the underlying condition; eliminate contributors (alcohol, other meds, smoking)
Switch to a lower-SD agent (bupropion, mirtazapine, vilazodone, vortioxetine, desvenlafaxine, duloxetine)
Add-on (off-label): bupropion, buspirone, sildenafil (best evidence, men), testosterone, mirtazapine — none FDA-approved for this purpose
Watch / wait + dose reduction in some cases

FDA-approved for HSDD: flibanserin (5-HT₁A agonist / 5-HT₂A antagonist) 100 mg qHS, for generalized, acquired HSDD in premenopausal women; ~50% respond, stop if no effect by 8 weeks. REMS (interaction with alcohol → hypotension/syncope; dizziness, somnolence, nausea, fatigue). For men, treat ED (PDE-5 inhibitors) and premature ejaculation separately.

⚕️ Attending-level pearls

SSRI-induced dysfunction is dose-dependent and rarely self-resolves. Options: dose reduction, switch to bupropion / mirtazapine / vortioxetine / vilazodone, or augment with bupropion, sildenafil (men), or buspirone.
Drug holidays are risky (discontinuation symptoms; ineffective for fluoxetine given its long half-life).
Lowest-SD antidepressants: bupropion, mirtazapine, nefazodone, vortioxetine. Flibanserin / bremelanotide for premenopausal HSDD.
Always look past the drug: the depression itself, the relationship, vascular/endocrine disease, and antipsychotic-induced hyperprolactinemia (adjunctive aripiprazole lowers prolactin).

Gender Dysphoria & Paraphilic Disorders Clinical Topic

Scope: DSM framing and pharmacotherapy for gender dysphoria and paraphilic disorders. Affirming care, minority stress, WPATH SOC-8, and population-level disparities → Populations → LGBTQ+ & Gender-Affirming Care.

Gender dysphoria

Marked incongruence between experienced/expressed gender and assigned sex, with clinically significant distress, ≥6 months
Gender identity itself is not a disorder — the diagnosis is the distress; care is affirming
Multidisciplinary, individualized care (psychological support, social transition, and — per guidelines — hormonal/surgical options); screen/treat high rates of depression, anxiety, suicidality

Paraphilic disorders

A paraphilia becomes a disorder only when it causes distress/impairment or harm/risk to others (e.g., nonconsent)
Examples: voyeuristic, exhibitionistic, frotteuristic, sexual sadism/masochism, pedophilic, fetishistic, transvestic
Management: CBT/relapse prevention; for risk reduction, SSRIs and (in severe cases) antiandrogens/GnRH agonists; forensic/legal considerations

Neuropsychiatry Clinical Topic

Scope: Psychiatric syndromes from primary neurologic disease. Organic differential for new presentations → Assessment → Medical Mimics. Delirium & hospital encephalopathies → C-L → Delirium.

Psychiatric syndromes arising from primary neurologic disease.

Condition	Psychiatric features	Pearls
Stroke	Post-stroke depression (~⅓), apathy, emotional lability/pseudobulbar affect, vascular cognitive impairment	Treat depression (SSRI); dextromethorphan-quinidine for pseudobulbar affect
Parkinson disease / DLB	Depression, anxiety, visual hallucinations, REM-sleep behavior disorder, impulse-control disorders (dopamine agonists)	Quetiapine/clozapine or pimavanserin for psychosis (avoid D₂ blockers — worsen motor); DLB = neuroleptic sensitivity
Huntington disease	Depression, irritability, OCD-like, psychosis, ↑suicide; chorea + cognitive decline	Autosomal dominant CAG repeat; VMAT2 inhibitors for chorea
Multiple sclerosis	Depression, pseudobulbar affect, euphoria, cognitive impairment; interferon → depression	—
Epilepsy	Interictal depression/psychosis (esp. temporal lobe), postictal psychosis; PNES (functional seizures)	PNES: video-EEG gold standard; treat as functional neurological disorder, not AEDs
Autoimmune (anti-NMDAR) encephalitis	Subacute psychosis, catatonia, dyskinesias, seizures, autonomic instability	Young women + ovarian teratoma; LP/antibodies/MRI/EEG; immunotherapy ± tumor removal
Frontal lobe syndromes	Dorsolateral → executive dysfunction; orbitofrontal → disinhibition; medial/anterior cingulate → apathy/abulia	Localizes behavior change; bvFTD mimics primary psychiatric illness

Localization quick-hits: temporal lobe → memory, déjà vu, complex hallucinations, psychosis; frontal → personality/executive/disinhibition; Klüver-Bucy (bilateral amygdala/temporal) → hyperorality, hypersexuality, placidity. Standard neuropsychiatry references (Kaplan & Sadock; APA neuropsychiatry).

Major neurocognitive disorders (dementias) — differentiating the subtypes

Type	Hallmark	Course / psychiatric features	Pathology / pearls
Alzheimer (AD)	Early short-term memory loss; word-finding, visuospatial	Insidious, gradual decline; later apathy, agitation, delusions (theft), wandering, sundowning	Amyloid plaques + tau tangles; ↓ ACh → cholinesterase inhibitors; APOE ε4 risk
Vascular	Stepwise decline; executive/processing slowing	Focal signs; depression/apathy common; correlates with vascular risk factors	Infarcts/white-matter disease; control BP, diabetes, lipids, antiplatelet
Lewy body (DLB)	Fluctuating cognition + recurrent visual hallucinations + parkinsonism	REM sleep behavior disorder; falls/syncope; delusions; the 3 core + supportive features	α-synuclein (Lewy bodies). Severe neuroleptic sensitivity — avoid typicals/high-potency; quetiapine/clozapine or pimavanserin; cholinesterase inhibitors help
Frontotemporal (FTD/bvFTD)	Early personality/behavior change & language, memory relatively spared	Disinhibition, apathy, loss of empathy, compulsions, hyperorality; often misdiagnosed as primary psychiatric illness (younger onset ~50s–60s)	Tau/TDP-43; frontotemporal atrophy; cholinesterase inhibitors not helpful (can worsen); SSRIs for behavior
Parkinson disease dementia	Motor parkinsonism ≥1 yr before dementia	Executive/visuospatial; hallucinations; depression/anxiety	If dementia <1 yr of/before motor signs → call it DLB ("1-year rule")
Rapidly progressive / reversible	Fast decline or treatable cause	—	Creutzfeldt-Jakob (myoclonus, EEG), NPH (gait/incontinence/cognition — "wet, wobbly, wacky"), B12, thyroid, neurosyphilis, NCSE

Parkinson disease — neuropsychiatric layer: depression & anxiety are very common (often precede motor signs); psychosis (visual hallucinations, often with retained insight early) — first reduce/simplify dopaminergic meds, then pimavanserin or low-dose quetiapine/clozapine (never high-potency D₂ blockers — worsen motor); impulse-control disorders (gambling, hypersexuality, shopping) from dopamine agonists (pramipexole/ropinirole) → reduce the agonist; REM sleep behavior disorder (melatonin/clonazepam); apathy & dementia late. DLB vs PDD = the 1-year rule. Movement-disorder/neuropsychiatry references.

TBI Treatment Special Topic

Symptom-targeted pharmacotherapy after traumatic brain injury.

Problem	Treatment	Mechanism
Depression / Anxiety	Sertraline, escitalopram, citalopram (SSRI); venlafaxine (SNRI)	SSRI / SNRI
Mania — acute	Quetiapine	5-HT/D₂ antagonist
Mania — maintenance	Valproate, carbamazepine, lithium	Block voltage-gated Na channels, ↑GABA
Agitation / Aggression	Propranolol / pindolol	Beta blocker
PTSD	Paroxetine (see depression)	SSRI
Psychosis	Risperidone, quetiapine, lurasidone	SGA
Apathy / Inattention	Methylphenidate, modafinil; zolpidem (apathy)	DA reuptake inhibitor; GABA agonist
Memory deficits	Donepezil, rivastigmine	Central AChE inhibitor
Executive function	Amantadine	Non-competitive NMDA antagonist; enhances dopaminergic transmission
OCD	SSRI	—

Avoid in TBI: Benzodiazepines (↑susceptibility, drowsiness, ataxia, slurred speech, memory impairment, disinhibition, aggravate fear); haloperidol / 1st-gen (slow neural recovery); anticholinergics (worsen mentation & memory).

Aggression & Violence — Psychopharmacology Clinical Topic

Scope: Acute agitation framework (Project BETA) and chronic aggression pharmacotherapy. General suicide/violence risk stratification → Assessment → Risk Assessment. Inpatient PRN order sets → Emergencies → PRNs.

Schizophrenia carries ~5–6× the violence risk of the general population, but only ~5% of violent crime is attributable to severe mental illness, and a small recidivist minority causes most incidents. Receiving antipsychotics cut violent crime ~45% in a national cohort (Fazel, Lancet 2014).

Medical vs primary-psychiatric agitation

Favors medical cause: age >40, no psych history, abnormal vitals/exam, sudden onset, visual hallucinations, emotional lability, can't sustain attention, ↓consciousness. Favors primary psychiatric: age <40, psych history, normal vitals/exam, gradual onset, auditory hallucinations, flat affect, redirectable, alert
Always screen for akathisia (iatrogenic) and substance withdrawal

Acute agitation (Project BETA)

Verbal de-escalation first; oral before IM; treat the cause; avoid seclusion/restraint where possible
Psychosis-driven agitation → antipsychotic preferred over benzodiazepine (addresses psychosis); SGA preferred over haloperidol
Can't cooperate with PO → IM ziprasidone or IM olanzapine
Alcohol/sedative withdrawal → lorazepam (also treats withdrawal)

Agent	Dose	Notes
Lorazepam	0.5–2 mg PO/IM/IV	Nonspecific; reliable IM absorption; no active metabolites; watch resp. depression / disinhibition
Haloperidol + lorazepam	5 mg + 2 mg IM	Faster + less EPS than haloperidol alone; same syringe
Olanzapine IM	10 mg (2.5–5 elderly)	Superior onset to haloperidol; do NOT combine with parenteral benzo (resp. depression/hypotension)
Ziprasidone IM	10–20 mg (20 > 10)	QTc not clinically different from oral/haloperidol
Inhaled loxapine	10 mg ×1/24 h	Rapid; REMS — bronchospasm, monitor 1 h
Asenapine SL	10 mg	Rapid (Tmax 30–90 min); off-label for agitation

NNT vs placebo for response at 2 h is low/favorable across IM SGAs, loxapine, and SL asenapine. IM aripiprazole 9.75 mg worked but is no longer manufactured.

Persistent aggression in schizophrenia — evidence hierarchy

Clozapine — strongest evidence; a selective anti-aggressive effect independent of antipsychotic/sedative action (Krakowski RCT: CLO > OLZ > HAL, no PANSS difference)
Olanzapine — 2nd; superior hostility reduction in EUFEST & CATIE post-hoc; available as LAI
Beta-blockers (propranolol 40–1600 mg; pindolol, nadolol) — 2nd-best; mostly brain-injured patients; delayed onset 4–6 wk; watch hypotension/bradycardia
Mood stabilizers — weak in schizophrenia (valproate ranked 1st in old consensus for aggression but RCT evidence thin); well-studied in bipolar
Antidepressants (SSRIs) — weak; benzodiazepines — negative evidence for chronic use (tolerance, withdrawal can worsen aggression)

Bottom line: treat the underlying disorder; no agent is FDA-approved for long-term aggression. Consider an LAI for nonadherent aggressive patients (paliperidone palmitate delayed time-to-treatment-failure incl. arrest vs oral).

⚕️ Attending-level pearls

Distinguish state from trait. Acute agitation needs rapid control; persistent aggression needs treatment of the underlying disorder, not standing PRNs.
Clozapine has the strongest anti-aggression evidence (Krakowski RCT — an effect independent of its general antipsychotic action); other SGAs reduce hostility (EUFEST/CATIE post-hoc).
Beta-blockers (high-dose propranolol) for organic/TBI aggression; valproate/lithium for impulsive aggression; SSRIs for impulsive aggression in personality disorders.
Avoid chronic benzodiazepines (paradoxical disinhibition). Best violence predictor = past violence; the biggest modifiable driver is substance use.

Genetics & Heritability Clinical Topic

Most psychiatric disorders are polygenic with substantial heritability; family history is a key risk factor and a useful clinical anchor.

Disorder	Approx. heritability	Notes
Bipolar disorder	~80–85%	Among the most heritable; ↑ risk in first-degree relatives
Schizophrenia	~80%	~10% risk with one affected parent; ~50% in monozygotic co-twin; copy-number variants (22q11)
Autism	~80%	Strong genetic/heritable component; sibling recurrence elevated
ADHD	~75%	Highly heritable; persists into adulthood in many
Major depression	~35–40%	Gene × environment; higher with recurrent/early-onset
Anxiety / OCD	~30–50%	OCD higher in early-onset/familial cases
Alcohol use disorder	~50%	Polygenic; ADH/ALDH variants modify risk
Borderline PD	~40–70%	Heritable temperament + trauma interaction

Single-gene/genomic syndromes with psychiatric features: 22q11.2 deletion (DiGeorge — high schizophrenia risk), Fragile X (intellectual disability/autism), Huntington (AD, CAG repeat), Wilson (AR, treatable — screen in young new-onset psychiatric + neuro/hepatic signs), velocardiofacial. Heritability ≠ determinism — environment, epigenetics, and gene×environment matter. Twin/family studies; standard psychiatric genetics references.

ECT & Neuromodulation Clinical Topic

Indications & efficacy (APA)

Major depressive episode (uni/bipolar): ~79%
Bipolar mania: ~80%
Catatonia: 60–80%
Schizophrenia: ~50%

Best candidates: psychotic/severe depression, elderly, high suicide risk, prior ECT response, pregnancy, when meds unsafe/intolerable, or patient preference. ECT resolves suicidal ideation rapidly. Effect size vs sham ≈ −0.9; ECT > antidepressants.

Course & technique

Index course: 6–12 treatments, 2–3×/week to remission
Maintenance: once q4–6 weeks
Electrode efficacy: bitemporal = bifrontal > right unilateral; square > sine wave
Ultrabrief pulse (≤0.3 ms) = less cognitive burden but brief pulse (0.5–1 ms) more effective
Ketamine anesthesia → better seizure quality, unclear outcome benefit

Workup & contraindications

Pre-ECT: history, surgical/anesthesia & prior ECT history, physical/neuro/dental exam
EKG + electrolytes if >40 yo. No absolute contraindications. Relative: unstable/severe CV disease (recent MI/CVA), severe pulmonary disease, ↑ICP / space-occupying lesion, ASA class 4–5

Side effects

Headache, jaw pain, myalgia (succinylcholine), nausea (→ ondansetron)
Postictal disorientation (<1 h); anterograde & retrograde amnesia (typically resolve 4–8 wk)
Interictal delirium — rare; classically with concomitant lithium (hold lithium)

Continuation is essential (relapse without it): post-ECT relapse 84% placebo vs 60% nortriptyline vs 39% lithium + nortriptyline; continuation-ECT ≈ Li+NTP. Medication-resistant patients relapse ~2× as often after ECT (68% vs 36%).

⚕️ Attending-level pearls

Electrode placement trade-off: bitemporal = fastest/most effective but most cognitive side effects; right unilateral ultrabrief = fewest cognitive effects but needs a higher dose (~6× seizure threshold); bifrontal is intermediate.
Continuation is non-negotiable — relapse approaches 50–84% within 6 months without continuation pharmacotherapy or maintenance ECT (Li + nortriptyline ≈ continuation ECT).
Lithium + ECT → prolonged seizures / delirium — hold or reduce lithium. Bupropion, clozapine, theophylline lower seizure threshold; benzodiazepines/anticonvulsants raise it (may need to hold).
Memory: anterograde amnesia recovers; retrograde (autobiographical) can persist
No absolute contraindications; relative: ↑ICP/space-occupying lesion, recent MI/stroke, unstable aneurysm

Psychotherapy — Modalities & Indications Clinical Topic

Evidence-based psychotherapies and where they're first-line — drugs and therapy are often additive.

Therapy	Core idea	Best evidence for
CBT	Identify & restructure maladaptive thoughts/behaviors	Depression, all anxiety disorders, insomnia (CBT-I), PTSD, OCD, eating disorders
Exposure / ERP	Graded exposure + response prevention; habituation/inhibitory learning	OCD (ERP), phobias, panic, PTSD (prolonged exposure)
Behavioral activation	Re-engage in rewarding activity	Depression (esp. low-resource settings)
DBT	Mindfulness, distress tolerance, emotion regulation, interpersonal effectiveness	Borderline PD, chronic suicidality/self-harm
IPT	Symptoms in interpersonal context (grief, role transition/dispute, deficits)	Depression, perinatal depression, bulimia
Psychodynamic	Unconscious conflict, transference, insight	Personality disorders, chronic relational patterns
ACT / MBCT	Acceptance & values (ACT); mindfulness to prevent relapse (MBCT)	Chronic conditions; MBCT for recurrent depression relapse prevention
Motivational interviewing	Resolve ambivalence, elicit change talk	Substance use, adherence, behavior change
CPT / EMDR	Trauma-focused cognitive processing / reprocessing	PTSD (trauma-focused therapy is first-line overall)

First-line therapy ≥ medication for: mild depression, most anxiety disorders, PTSD (trauma-focused), OCD (ERP), borderline PD (DBT), and insomnia (CBT-I). Combine with pharmacotherapy for moderate–severe illness. APA practice guidelines; Cochrane reviews.

Substance Use & Addiction

Principles → primary substances → miscellaneous intoxicants & special situations

Principles & Guidelines

Primary Substances

Miscellaneous & Special Situations

Addiction — Principles Substance Use

Core neurobiology

All major drugs of abuse (nicotine, alcohol, opioids, cocaine, amphetamines) increase dopamine in the nucleus accumbens (brain reward center)
Addiction is a chronic, relapsing brain disease with volitional use at the start → involuntary behavior in the dependent state

Cocaine/amphetamines acutely ↑ but chronically deplete DA & glutamate
Nicotine also ↑ serotonin in the amygdala

Tolerance ≠ dependence ≠ addiction

Tolerance/withdrawal are neither necessary nor sufficient for addiction
Addiction = drug use "out of control" — not necessarily daily use, tolerance, physiologic dependence, or withdrawal
Patients can have tolerance/withdrawal without addiction (e.g., chronic opioid pain patients), and addiction without much tolerance/withdrawal

Risk of addiction among those who ever use (Anthony 1994)

Drug	Ever used	Became dependent	Conditional risk
Tobacco	75.6%	24.1%	31.9% (highest)
Heroin	1.5%	0.4%	23.1%
Cocaine	16.2%	2.7%	16.7%
Alcohol	91.5%	14.1%	15.4%
Cannabis	46.3%	4.2%	9.1%

Agent–Host–Environment model. Agent: availability, dose, price, purity. Host: heredity, rapidity of tolerance, metabolism, reward magnitude, psychiatric comorbidity ("self-medication"). Environment: role models, stress, peer pressure. Relapse drivers: psychiatric problems (depression, anxiety), social problems, protracted abstinence, and conditioned cue-induced craving (persists for years via changes in gene transcription).

Cross-tolerance guides detox substitution: heroin → methadone; alcohol → a benzodiazepine (e.g., oxazepam/chlordiazepoxide). Comorbidity ("dual diagnosis") is the norm, not the exception.

VA/DoD SUD Guideline (2021) Evidence-Based

Key graded recommendations from the VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders (2021). Strong = "we recommend"; Weak = "we suggest."

Alcohol use disorder — pharmacotherapy

STRONG (first-line): naltrexone (oral or XR) or topiramate
WEAK: acamprosate or disulfiram
If first-line contraindicated/ineffective → gabapentin (weak)
Pair with psychosocial: CBT, motivational enhancement, community reinforcement, behavioral couples therapy, or 12-step facilitation (weak)

Opioid use disorder — pharmacotherapy

STRONG (first-line): buprenorphine/naloxone (any setting) or methadone (via an accredited OTP)
WEAK: extended-release naltrexone (IM)
Insufficient evidence to prefer one buprenorphine formulation, or for oral naltrexone
MOUD reduces all-cause & overdose mortality — the core intervention

Withdrawal management

Alcohol: benzodiazepines for moderate–severe; if benzo risk > benefit → carbamazepine, gabapentin, or valproic acid. Use fixed-schedule or symptom-triggered (CIWA-Ar) taper
Inpatient alcohol withdrawal if CIWA-Ar ≥20, or history of DTs/withdrawal seizures, can't tolerate PO, risky comorbidity, or polysubstance withdrawal
Opioid: taper with buprenorphine or methadone (OTP/inpatient); clonidine or lofexidine 2nd-line
Benzodiazepines: gradual taper (don't stop abruptly)

Screening & care model

Screen all for unhealthy alcohol use periodically (AUDIT-C or validated single-item)
Brief intervention = express concern → advise (cut down/abstain) → feedback linking use & health → refer to treatment
Addiction-focused medical management: monitor adherence/response/adverse effects, educate, encourage abstinence & community supports/lifestyle change
Stimulant & cannabis use disorder: insufficient evidence for any pharmacotherapy → psychosocial (e.g., contingency management)

Source: VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders, 2021 (GRADE).

Alcohol Use Disorder Substance Use

Withdrawal & emergencies

Withdrawal: agitation, tremor, autonomic hyperactivity, anxiety, insomnia, nausea, seizures. Treat with benzodiazepines (chlordiazepoxide, lorazepam, diazepam).
Delirium tremens: 2–4 days after last drink; AMS/hallucinations, autonomic instability, seizures. Medical emergency → benzodiazepines.
Wernicke encephalopathy (triad): ataxia, ophthalmoplegia, confusion (+ alcohol history). Hyperthermia is NOT part of it. → give thiamine before glucose
Untreated → Korsakoff (irreversible amnesia, confabulation)

Medications for AUD

Naltrexone (μ-opioid antagonist): ↓ heavy drinking days vs placebo. PO or long-acting IM (Vivitrol). Opioid peptides mediate alcohol reward → blocking ↓ reward. Best response when used to satisfy craving (less for those drinking to self-medicate distress).
Acamprosate (Campral): relapse prevention (glutamatergic modulation).
Disulfiram (Antabuse): aldehyde dehydrogenase inhibitor — aversive reaction.

Pharmacogenetics: The OPRM1 A118G (Asp40) allele predicts better naltrexone response (COMBINE study: good outcome 87% vs lower in Asn40 homozygotes). Asp40 binds β-endorphin with ~3× greater potency.

Medical complications

Hepatic: steatosis → alcoholic hepatitis (AST:ALT >2:1, ↑bilirubin) → cirrhosis (varices, ascites, coagulopathy, HCC); accelerates HCV
Pancreatitis (↑amylase/lipase)
Cancers: mouth, throat, esophagus, liver, breast
Fetal alcohol syndrome; ~23% of suicides attributable to alcohol

Withdrawal — timeline & management (CIWA-Ar)

Stages after the last drink

~6–12 h: anxiety, tremor, headache, ↑HR, insomnia, restlessness
~24 h: alcoholic hallucinosis / perceptual disturbances (intact sensorium)
~48 h: withdrawal seizures
~72–96 h: delirium tremens (confusion, agitation, hallucinations, severe autonomic hyperactivity) — high mortality

DT risk: prior severe withdrawal/DTs, heavy chronic use, age >40, comorbidities, withdrawal while still intoxicated. CIWA-Ar: <8–10 mild, 8–15 moderate, ≥15 severe (impending DTs).

Treatment

Benzodiazepines = mainstay. Long-acting (chlordiazepoxide, diazepam) give a smoother course; lorazepam preferred in elderly/liver disease (no oxidative metabolism, no active metabolites)
Strategies: symptom-triggered (CIWA-driven; less total drug, shorter — preferred for most), fixed-schedule (if monitoring unreliable or high complication risk), or front-loading (long-acting agent self-tapers)
Phenobarbital for benzo-refractory; dexmedetomidine/propofol as ICU adjuncts; neuroleptics only adjunctively (lower seizure threshold)
Thiamine before glucose; author dose: 500 mg IV TID ×3 d → 250 mg daily ×5 d. Repletion of fluids/electrolytes/folate

Symptom-triggered management algorithm

1Screen & risk-stratify

Confirm AUD (AUDIT-C / CAGE); give thiamine before glucose (500 mg IV TID), fluids, electrolytes, folate
Assess DT risk: prior DTs/seizures, heavy chronic use, age >40, comorbidity

↓

choose strategy

2Reliable monitoring available?

Yes → symptom-triggered (preferred): CIWA-Ar q1h (moderate) / q4–6h (stable)
No (or high complication risk) → fixed-schedule taper or front-loading (long-acting benzo self-tapers)

↓

dose by CIWA-Ar score

3Benzodiazepine (mainstay)

CIWA 8–15 → PO benzo PRN; ≥16 → parenteral. Use lorazepam if elderly / liver disease
e.g., lorazepam 1–4 mg or chlordiazepoxide 25–50 mg or diazepam 10–20 mg

↓

benzo-refractory / severe

4Escalate (ICU)

Phenobarbital; dexmedetomidine (noradrenergic surge) or propofol (often ventilated) for refractory DTs

↓

stabilized

5Engage in recovery

Motivational interviewing → MAT (naltrexone/acamprosate), psychotherapy, 12-step/peer support

Source: ACLP "How-To Guide: Alcohol Withdrawal" (Issac, 2022).

Sedative Use Disorder, Taper & Harm Reduction Substance Use

Sedative-hypnotic (benzodiazepine) use disorder

Tolerance, dose escalation, use despite harm; high-risk with opioids/alcohol (additive respiratory depression)
Withdrawal is potentially life-threatening (seizures, delirium) — never stop abruptly
Taper: convert to a long-acting agent (diazepam/chlordiazepoxide), reduce slowly (~5–10%/1–2 wk; slower at the end); adjunct gabapentin/carbamazepine; phenobarbital protocols for complex cases
Z-drugs (zolpidem/zaleplon/eszopiclone) carry similar dependence/withdrawal risk

Harm reduction & dual diagnosis

Naloxone distribution (take-home), fentanyl test strips, syringe-service programs (↓ HIV/HCV), supervised consumption, not requiring abstinence to engage
MOUD (methadone/buprenorphine) reduces overdose death — see Opioid section
Dual diagnosis: treat psychiatric and substance disorders concurrently (integrated care), not sequentially; high comorbidity (mood, PTSD, psychosis)
Stimulant use disorder: no FDA-approved medication → contingency management is most effective

Opioid Use Disorder Substance Use

Intoxication & withdrawal

Opioid actions: analgesia, euphoria, sedation, respiratory depression, miosis (pupil constriction), constipation, ↓GI motility, nausea, ↑prolactin, antitussive.

Overdose: CNS depression → coma, ↓respiratory rate, ↓brainstem CO₂ responsiveness
Reverse with naloxone (Narcan, IM/nasal)

Withdrawal (not life-threatening): sweating, yawning, anxiety, ↑BP/RR, cravings, lacrimation, piloerection, rhinitis, abdominal cramps, diarrhea.

Intrinsic activity spectrum

Full agonist: methadone (oral, long-acting, cheap; "blocking dose"). Watch QT prolongation at high dose.
Partial agonist: buprenorphine (ceiling effect → safer in overdose). Suboxone = buprenorphine + naloxone: SL → buprenorphine predominates; if injected → naloxone precipitates withdrawal (abuse deterrent).
Antagonist: naltrexone (relapse prevention; non-addicting, no diversion); naloxone (reversal).

Treatment options: detox via agonist taper and/or clonidine (eases autonomic symptoms); substitution/MAT with methadone or buprenorphine; relapse prevention with naltrexone (PO or depot IM). Methadone maintenance reduces IV use, crime, and HIV transmission. Methadone historically confined to federal/state-regulated programs.

Methadone vs Buprenorphine — practical comparison

	Methadone	Buprenorphine (± naloxone = Suboxone)
Pharmacology	Full µ-agonist	Partial µ-agonist (ceiling effect → safer in OD)
Half-life / dosing	Long (~7 d at steady state); daily clinic early on	Long-acting; dosed daily up to weekly/monthly maintenance
Key risks	QTc prolongation, respiratory depression	Precipitated withdrawal if given too early; minimal respiratory depression
Start timing	Few restrictions; monitor COWS	Must be in withdrawal first (tachy, HTN, mydriasis, yawning, ↑bowel sounds, diaphoresis)
Choose when	Patient still needs opioids for pain; cost-sensitive; not for QT-prolongation patients	Concerned about QT; no ongoing opioid-analgesia need; wants office-based / less-frequent dosing

Induction (inpatient, illustrative): Methadone — start 5–10 mg, reassess q1–2 h, add 5–10 mg until symptoms resolve (avoid sedation); most patients ≤30–40 mg/day. Buprenorphine — start 2–4 mg once mild–moderate withdrawal present, +2–4 mg after 1–2 h; typical target 8–16 mg/day (max ~24–32 mg). Post-discharge: up to ~3 days of medication before an outpatient prescription is required. ⚠️ Verify against current institutional and DEA/SAMHSA protocols.

Buprenorphine microinduction (low-dose initiation)

Why: standard induction requires the patient to be in withdrawal first (avoids precipitated withdrawal), which is a barrier. Microinduction introduces small (≤1 mg) slowly-increasing buprenorphine doses alongside the full agonist, then tapers the full agonist after a therapeutic dose is reached — staying below the withdrawal threshold.

Choose for: recent high-potency/long-acting opioid use (fentanyl), prior intolerance of withdrawal/standard induction, time-limited hospitalization, ongoing full-agonist pain treatment, or a rapid methadone→buprenorphine transition.

Bernese (7-day outpatient): SL 0.5 mg daily → 0.5 mg BID → 1 mg BID → 2 mg BID → 3 mg BID → 4 mg BID → day 7: 12 mg and stop other opioids
Hospital (IV→SL): e.g., IV 0.15 mg q6h → 0.3 → 0.6 mg q6h (begin 25%/day full-agonist taper) → switch to SL bup-naloxone 4-1 mg q6h → 8-2 mg BID; 0.15 mg IV ≈ 0.5 mg SL
Slower titration (5-day) lowers precipitated-withdrawal risk vs 3-day; max ~24 mg/day

MATE Act (2023): no X-waiver needed to prescribe buprenorphine (DEA registration still required outpatient); no DEA license needed for inpatient withdrawal management of a patient hospitalized for another problem. Source: ACLP "How-To Guide: Buprenorphine Microinduction" (Archer & Schnipke, 2024).

Stimulants — Cocaine & Amphetamines Substance Use

Toxicity

Cocaine (blocks NE/DA reuptake → sympathomimetic): vasospasm → MI, CVA
arrhythmias, seizures, hypertensive bleeds, cardiomyopathy/myocarditis
hyperpyrexia, rhabdomyolysis → renal failure
nasal septal perforation
"crack lung." Cocaine + alcohol → cocaethylene (cardiotoxic). Speedball = cocaine + heroin

Cocaine chest pain: O₂, aspirin, nitroglycerin, benzodiazepines. Avoid β-blockers (unopposed α). For cocaine aortic dissection → β-blockers (avoid aspirin).

Methamphetamine & withdrawal

Methamphetamine: more neurotoxic than cocaine
dilated cardiomyopathy, psychosis, paranoia, formication ("bugs crawling"), severe dental/dermatologic
Protease inhibitors can ↑ meth levels 3–10× in HIV patients

Cocaine withdrawal (not dangerous, but severe WD predicts poor outcome): anergia, depression, hypersomnia, hyperphagia, bradycardia, psychomotor retardation, poor concentration.

Treatment: No medication has robust proven efficacy for stimulant use disorder; psychosocial treatment (contingency management/vouchers, drug counseling) is mainstay. Agents with positive DB-trial signals: modafinil (glutamate-enhancing, blocks euphoria), disulfiram (↑ brain DA via DBH inhibition), topiramate (relapse prevention), baclofen (cue craving), propranolol (severe withdrawal). The DA antagonist olanzapine worsened outcomes. NAC normalizes glutamate (studied for craving).

Cannabis Use Disorder Substance Use

The most commonly used federally-illicit drug; THC is a partial agonist at CB₁ receptors. Rising potency and concentrates increase risk.

Intoxication & risks

Intoxication: euphoria, ↑appetite, conjunctival injection, dry mouth, tachycardia, impaired coordination/time perception, anxiety/paranoia; high doses → transient psychosis
Psychosis link: dose-dependent ↑ risk of psychotic disorder, esp. high-potency/early-adolescent use; can precipitate/worsen schizophrenia
Cognitive effects (attention/memory) with heavy chronic use; ↑ anxiety/depression associations
Cannabinoid hyperemesis syndrome (CHS): cyclic vomiting + compulsive hot showers/baths; resolves with cessation (topical capsaicin acute)

Withdrawal & treatment

Withdrawal (DSM-5-TR): irritability, anxiety, sleep disturbance/vivid dreams, ↓appetite, restlessness, depressed mood, physical symptoms; onset 1–3 d, peak ~1 wk
No FDA-approved medication for cannabis use disorder
Psychosocial first-line: CBT, motivational enhancement, contingency management
Symptomatic for withdrawal/sleep; treat comorbid mood/anxiety/psychosis

Note: distinguish prescription cannabinoids (dronabinol, nabilone — antiemetic/appetite; cannabidiol/Epidiolex — seizure) from recreational use. Synthetic cannabinoids ("K2/Spice") are far more potent CB₁ agonists with severe agitation, psychosis, seizures, and unpredictable toxicity. DSM-5-TR; ASAM/standard addiction references.

Tobacco / Nicotine Cessation Substance Use

Pharmacology

Nicotine reaches the brain in seconds
intake ~1 mg/cigarette
half-life ~120 min
85–90% hepatic metabolism. → ↑DA (nucleus accumbens, reward) and ↑5-HT (amygdala)
Smoking is positively (pleasure) and negatively (withdrawal avoidance) reinforced

Smoking induces CYP1A2 → lowers levels of some antipsychotics (clozapine, olanzapine) & others
smokers may need higher doses, and stopping can raise levels

Cessation — relative efficacy

Highest quit rates: combined nicotine patch + bupropion (though combo not always significantly > bupropion alone).
Bupropion (Zyban): start 7–14 d before quit date, 300 mg × 7–12 wk; ~doubles quit rates. Avoid w/ seizure or eating disorder.
NRT: patch (21/14/7 mg taper), gum (4 mg > 2 mg for dependent), lozenge, nasal spray (fastest), inhaler — all ~double placebo.
Strongest motivator = health concerns; brief physician advice is one of the strongest interventions.

5 A's: Ask, Advise, Assess, Assist, Arrange follow-up. Psychiatric populations smoke ~44% of all cigarettes, are heavier smokers, and may use nicotine to self-medicate. Bupropion effective in schizophrenia & depression; fluoxetine for those with depression history.

Miscellaneous Intoxicants & Club Drugs Substance Use

Scope: Acute intoxication and tox management for agents not covered in their own sections. Benzodiazepine dependence/taper → Sedative Use Disorder. Cannabis use disorder & chronic effects → Cannabis Use Disorder.

Agent	Mechanism / intoxication	Key risks & management
LSD / psilocybin (classic hallucinogens)	5-HT₂A agonist; perceptual distortion, synesthesia, depersonalization; dilated pupils	"Bad trips" → reassurance/quiet room, benzodiazepine; HPPD (flashbacks); no significant physical dependence
PCP / ketamine (dissociatives)	NMDA antagonist; dissociation, analgesia; PCP → violence, nystagmus (rotary), ↑BP, numbness	Agitation → benzodiazepines (± antipsychotic); minimize stimulation; rhabdo/hyperthermia. Ketamine/esketamine also a rapid antidepressant
MDMA ("ecstasy/molly")	Serotonin/NE release; empathogenic, ↑energy	Hyperthermia, hyponatremia (water intoxication), serotonin syndrome, bruxism; supportive cooling
GHB	GABA-B; euphoria → sedation	Respiratory depression/coma (narrow margin, esp. with alcohol); withdrawal resembles alcohol/benzo (can be severe)
Inhalants	Solvents/nitrites; rapid CNS depression	Youth; "sudden sniffing death" (arrhythmia); neurotoxicity with chronic use
Benzodiazepines (acute intoxication)	Potentiate GABA-A; anterograde amnesia, confusion (elderly)	Supportive; flumazenil (caution — seizures). For dependence/taper → Sedative UD section
Barbiturates	Potentiate/mimic GABA, block glutamate; narrow therapeutic index	Respiratory depression → airway/supportive care
Anticholinergics	Atropine, diphenhydramine, TCAs, OTC sleep aids, benztropine	Delirium + fever, dry skin, mydriasis, tachycardia, ↓peristalsis, urinary retention; physostigmine if severe
Caffeine	Adenosine antagonist	Intoxication (>~250 mg) and withdrawal (headache, fatigue) are DSM-5-TR conditions

DSM-5-TR; standard toxicology/addiction references.

Substance Use in Pregnancy & Neonatal Effects Substance Use

Acute & neonatal effects

Substance	Pregnancy disruption	Neonatal
Nicotine	Spontaneous abortion, premature delivery, IUGR, SIDS	Growth retardation, jittery, withdrawal
Alcohol	Fetal demise	Fetal alcohol syndrome (growth retardation, short palpebral fissures, flat midface, thin upper lip, indistinct philtrum, CNS dysfunction); 1–3/1000 births
Cocaine	Spontaneous abortion, abruptio placentae, premature delivery/PROM, fetal demise	Growth retardation, irritability, ↑tone
Opiates	—	Neonatal abstinence syndrome (60–90% of exposed); irritability, ↑tone, poor feeding, high-pitched cry, seizures, within 72 h

NAS supportive care: swaddling/containment, quiet low-light environment, gentle handling; opioids (tincture of opium, oral morphine, methadone) for severe symptoms. Drugs that block NMDA or activate GABA-A (alcohol, PCP, ketamine, barbiturates, benzodiazepines) trigger widespread neuronal apoptosis during the brain growth spurt.

Medical Complications of Injection Drug Use Substance Use

Infectious (most are Staph. aureus)

Endocarditis — right-sided (tricuspid, pulmonary) classic for IDU; S. aureus most common
Skin/soft tissue: cellulitis, abscess, fasciitis (MRSA, Pseudomonas); clostridial (tetanus, wound botulism, gas gangrene)
Bone/joint: osteomyelitis, septic arthritis (incl. sternoclavicular), vertebral osteo, spinal epidural abscess → paralysis
Bloodborne viruses: HIV, HBV, HCV, HDV, HTLV; endophthalmitis; brain abscess
Renal: "heroin nephropathy" (sclerosing GN)

Non-infectious

Talc granulomas (CXR nodules) from particulate fillers
Air embolism, septic thrombophlebitis, mycotic aneurysm
Pneumothorax (jugular attempts), cotton fever (endotoxin)
Fentanyl-laced heroin → overdose deaths
Anabolic steroids: atherogenic lipids, hepatic tumors, mania/aggression. EPO → polycythemia.

Consult-Liaison Psychiatry

Consult process → acute neuropsych → mood/coping → safety & end-of-life → behavioral plans

Consult Process

Acute Neuropsychiatric

Mood & Coping on the Medical Service

Safety, End-of-Life & Procedures

Behavioral Management

How to Do a Psychiatric Consult Consult-Liaison

The C-L consult is a structured process: clarify the real question, gather data from every source, interview skillfully in a non-private setting, then communicate practical recommendations the primary team can act on.

Clarify the question first

Talk to the primary team directly — the written reason is often too broad, too narrow, or not something psychiatry can do
Negotiate a focused, answerable question

Clear: assess for depression/anxiety, evaluate Δ mental status, capacity assessment, manage agitation, assess SI/HI, reasons for non-adherence, detox. Vague: "patient is difficult," "transfer off our service," "make the patient adherent," "can we discharge?"

Review the chart before you walk in

Prior psychiatry/neurology notes; PDMP
Meds — psychotropics & neuropsychiatric culprits (opioids, steroids, anticholinergics), QT-prolongers, interactions
Brain imaging, labs, EKG (QTc), EEG; vitals (withdrawal, infection, hypoxia)

Interview, examine, and synthesize

Rapport: clarify your role, whether the patient knew about the consult, and why you're there; address privacy; interview adults alone first; treat discomfort (pain, thirst, position) before evaluating; leave them with a concrete formulation and plan
History nuance: determine how much the medical illness/medication drives the symptoms; is this a normal stress response vs a disorder?; assess character style and coping; address mortality & spirituality
Exam: full MSE + a cognitive exam (MoCA/SLUMS — but a MoCA during delirium isn't the baseline); targeted neuro exam for toxicity/catatonia
Collateral: family, outpatient providers, and especially the bedside nurse
Formulate bio-psycho-socially; provisional dx/plan are acceptable pending data

Close the loop: verbally communicate recommendations to the primary team (preferred over texting/notes alone) and document whom you told. The recommendation section may be all the consultee reads — make it practical, jargon-free, and clear about who manages what. Avoid "chart wars." Include a safety assessment and an explicit follow-up plan. Daily follow-up for restraints, 1:1, severe agitation, suicidality, instability, or newly-started psychotropics; one-time consults may suffice for capacity, transplant clearance, or low-burden cases. Source: ACLP "How-To Guide: Doing a Consult" (Ernst; Brogoch & Dragonetti, 2024).

Delirium — Diagnosis, Prevention & Management Consult-Liaison

DSM-5-TR: an acute, fluctuating disturbance of attention and awareness caused by an underlying medical condition, substance, or medication. It is a medical emergency — find and fix the cause.

Five diagnostic features

Disturbance of attention & awareness
Acute onset (hours–days), a change from baseline, fluctuating through the day
An additional cognitive disturbance (memory, orientation, language, visuospatial, perception)
Not better explained by another neurocognitive disorder; not in the context of coma
Evidence it is caused by a medical condition, intoxication/withdrawal, or medication

ABCs of delirium: Affect (anxiety, paranoia, irritability), Behavior (hyper-/hypoactive, restlessness), Cognition. Hypoactive delirium is most often missed.

Pathophysiology

Widespread neural-network disturbance; ↓ cholinergic + ↑ dopaminergic activity (why anticholinergics worsen it and antipsychotics help)
Drivers: direct brain insults (hypoxia, hypoglycemia, hyponatremia, stroke, trauma, drugs), exaggerated stress response, and neuroinflammation (↑ cortisol, cytokines)

Etiologies & targeted workup

Category	Examples	Workup
Drugs (intoxication/withdrawal)	Alcohol, sedative-hypnotics, stimulants, hallucinogens; prescription effects	UDS, serum drug levels; empiric thiamine (don't wait for a level)
Metabolic / endocrine	Hyponatremia, hyperammonemia, uremia, hypothyroidism, vitamin deficiency	BMP, LFTs, CBC, UA, TSH, B12/folate, ammonia, cortisol
Trauma	TBI, subdural hematoma	Neuroimaging, EEG
Infection	Meningitis, neurosyphilis, HIV, bacteremia, fungal	HIV, RPR, CSF analysis, cultures
Cerebrovascular	Stroke, SAH, seizures	Neuroimaging, EEG
Autoimmune / cardiac / other	CNS vasculitis, SLE; heart failure, endocarditis; post-op, DIC, dysthermia	CRP/ESR, autoantibodies; echo, cardiac enzymes, EKG

No clear cause is found in ~10% of cases.

Non-pharmacologic (prevention & treatment) — first-line

Reorient (lighting, clock, calendar, familiar objects); hearing aids/glasses
Early mobilization — the only intervention shown to ↓ ICU length of stay
Protect the sleep-wake cycle; minimize overnight interruptions
Treat pain, hydrate, nutrition, bowel/bladder; remove unnecessary catheters/lines
Minimize restraints & psychoactive polypharmacy; staff continuity; sitters over restraints
ICU: the ABCDEF bundle (pain, SAT/SBT, analgesia/sedation choice, delirium, early mobility, family)

Pharmacologic (no FDA-approved agent)

Antipsychotics (high- or low-potency) for distress/agitation — monitor QTc
Valproic acid for hyperactive/agitated delirium in selected cases
Alpha-2 agonists (dexmedetomidine, clonidine, guanfacine); melatonin/ramelteon
Benzodiazepines — reserve for alcohol/sedative withdrawal (otherwise can worsen delirium)
Avoid anticholinergics. Medication treats symptoms, not the delirium itself

Management algorithm

1Recognize & confirm

Acute, fluctuating inattention + cognitive change; screen with CAM
Look for hypoactive (most missed)

↓

find the cause

2Identify & treat the etiology

Workup: glucose, BMP/LFTs/CBC/UA, TSH, B12, UDS, empiric thiamine; EKG; head CT/EEG/LP as indicated
Remove deliriogenic drugs (anticholinergics, benzodiazepines, opioids, steroids); treat infection/hypoxia/metabolic

↓

always — first-line

3Non-pharmacologic bundle

Reorient, restore sleep-wake cycle, early mobilization, glasses/hearing aids, hydration, minimize lines/restraints (sitter)

↓

distress / danger persists

4Targeted pharmacotherapy (symptom control only)

Antipsychotic for agitation/distress (e.g., haloperidol, low-dose SGA) — monitor QTc
Alpha-2 agonist (dexmedetomidine) in ICU; melatonin; valproate for hyperactive cases
Benzodiazepines only for alcohol/sedative withdrawal. Avoid anticholinergics

↓

resolution

5Taper & reassess cognition

Stop the psychoactive agent as delirium clears; document and reassess baseline (a MoCA during delirium ≠ baseline)

ICU delirium — SCCM PADIS guideline (2018, focused update 2025)

Screen routinely with a validated tool — CAM-ICU or ICDSC (delirium is a clinical diagnosis; screening detects it, esp. hypoactive)
Delirium treatment (2025): no recommendation for or against antipsychotics (haloperidol or atypical) — they have minimal/no effect on delirium duration, ICU/hospital stay, or mortality. The 2018 statin recommendation (against) stands
Short-term antipsychotics remain reasonable only for distressing symptoms (hallucinations, delusional fear) or dangerous agitation — and stop them once the distress resolves
Sedation (2025): dexmedetomidine suggested over propofol for light sedation in ventilated adults (less delirium, more time at target; accept slight bradycardia risk) — and both are preferred over benzodiazepines
Multicomponent non-pharmacologic prevention (the ABCDEF bundle) remains the core evidence-based strategy

PADIS 2025 — other focused-update changes (all conditional)

Anxiety (new topic): insufficient evidence for benzodiazepines; assess with a validated tool and try non-pharmacologic options (music, virtual reality)
Immobility: enhanced mobilization over usual care (cycling, early initiation, twice-daily, protocol-driven) — benefits to function/QoL outweigh slight arrhythmia risk
Sleep: melatonin suggested as a low-risk option to improve sleep quality and reduce delirium

Sources: Devlin et al., Crit Care Med 2018;46(9):1532–48; Lewis et al. (focused update), Crit Care Med 2025;53(3):e711–e727. All conditional, low/very-low-quality evidence.

Source: ACLP "How-To Guide: Delirium" (Schwartz et al.; updated 2025).

Catatonia Consult-Liaison

A psychomotor syndrome that occurs in psychiatric (mood > schizophrenia), neurologic, and medical illness. Most common signs are immobility and mutism, then rigidity. It may be stuporous (withdrawn) or excited (agitated), and a malignant form with hyperthermia + autonomic instability requires ICU care.

Recognize & screen — Bush-Francis (BFCRS)

23-item scale; screen with items 1–14 (≥2 present = positive). In critically ill medical patients, ≥4 signs = 91% sens/91% spec
Classic signs: immobility/stupor, mutism, staring, posturing/catalepsy, waxy flexibility, negativism, echopraxia/echolalia, Mitgehen ("anglepoise"), Gegenhalten, grasp reflex, automatic obedience
Bedside mnemonic "A SLIME-Posture": Acute onset + ≥2 of — Speech/Latency, Interaction (stupor), Muscle (rigidity/waxy), Eyes (staring), Posturing
Consider catatonia in any persistent delirium — do a BFCRS; ≥4 signs → presumed medical catatonia

Neuromedical workup

CMP, CBC w/ diff, UA, HIV/RPR, CXR; TSH; UDS; CK + iron (ferropenia & ↑CK in malignant)
MRI (stroke/mass), EEG (seizure), EKG
LP + autoantibodies (anti-NMDA-receptor, anti-VGKC) for encephalitis/paraneoplastic

Differential spans psychiatric (mood, conversion), neurologic (PD, Lewy body), and medical (Wilson, DKA); distinguish "cannot interact" (catatonia, akinetic mutism, locked-in) from "will not" (malingering, factitious).

Treatment algorithm — lorazepam challenge → ECT

1Stabilize & stop offenders

Stop antipsychotics / dopamine depleters; restart any recently-withdrawn dopamine agonist
Supportive care: hydration, nutrition, VTE prophylaxis, aspiration precautions; obtain ECT consent early

Malignant features (fever, autonomic instability, rigidity) → ICU + go straight to ECT.

↓

diagnostic + therapeutic

2IV lorazepam challenge

Lorazepam 2 mg IV (1 mg if frail/elderly/pediatric); reassess + repeat BFCRS at 30–120 min
No effect → repeat the same dose; may repeat again in 2 h

↓

partial / positive response

3Standing lorazepam

Give ≥6 mg/24 h to judge adequacy, then 2 mg IV q6–8h ×3–4 days (longer if catatonia >1 month)
After lysis → switch to SL/PO lorazepam to maintain. Monitor for respiratory depression

↓

no/inadequate response, or malignant

4ECT

Effective in 80–90%; first-line for malignant catatonia; bitemporal, daily if severe → taper frequency as it lifts

↓

refractory / no ECT access

5Alternatives

Valproate, NMDA antagonists (memantine/amantadine), zolpidem. Avoid antipsychotics (NMS / malignant-catatonia risk)

Source: ACLP "How-To Guide: Catatonia" (Rustad; updated 2025).

Organ-System & Drug-Induced Encephalopathies Consult-Liaison

Common medical causes of altered mental status / "psychiatric" presentations on the consult service (all forms of delirium — find & treat the cause).

Cause	Features	Management
Hepatic encephalopathy	Confusion → coma, asterixis, ± ↑ammonia; precipitants: GI bleed, infection, constipation, sedatives	Lactulose (titrate to 2–3 soft stools), rifaximin; treat precipitant; avoid sedatives/benzos (use cautiously); prefer LOT benzos if essential
Uremic encephalopathy	Confusion, asterixis, myoclonus, seizures with renal failure	Dialysis; renally dose all psychotropics (see Renal/Hepatic)
Hypercapnic / hypoxic	CO₂ narcosis (COPD), somnolence; hypoxia → agitation/confusion	Correct gas exchange; avoid respiratory depressants
Steroid-induced	Mania/psychosis/depression/insomnia; dose-related (esp. >40 mg prednisone)	Taper/lower steroid if possible; antipsychotic for mania/psychosis; lithium can prevent/treat steroid mania; watch mood on taper
Wernicke encephalopathy	Confusion, ophthalmoplegia, ataxia (often incomplete triad)	IV thiamine before glucose; high-dose repletion (see Alcohol)
Endocrine / electrolyte	Thyroid, glucose, Na⁺/Ca²⁺ derangements, adrenal (see Medical Mimics)	Correct the underlying abnormality

Approach: these are delirium — workup & treat the cause (see Delirium); use antipsychotics sparingly for agitation with QTc awareness; minimize deliriogenic drugs (anticholinergics, benzodiazepines except withdrawal); reorient and protect sleep-wake cycle. General hospital psychiatry / ACLP references.

Depression in the Medically Ill Consult-Liaison

Depressive symptoms are common in CAD, diabetes, hypothyroidism, HIV, cancer, stroke, epilepsy, MS, and Parkinson's. The CL task is to sort the four causes and use an inclusive diagnostic approach (count somatic symptoms — it is more sensitive when physical illness overlaps).

Differential — four buckets

Due to a medical condition (physiologic effect of the illness)
Substance/medication-induced — alcohol/opioids/benzos; stimulant withdrawal; and many drugs (interferon-α, corticosteroids, efavirenz, propranolol/β-blockers, clonidine/α-methyldopa, varenicline-era agents, isotretinoin, metoclopramide, anticonvulsants)
Adjustment disorder with depressed mood (may progress to MDD/persistent depressive disorder)
Primary MDD

Mimics to exclude first

Hypoactive delirium — withdrawal, apathy, slowing; distinguish by sudden onset, inattention, sleep-wake disturbance, cognitive deficits
Demoralization — loss of meaning/helplessness but can still experience pleasure (vs anhedonia in depression)
Workup: CBC, BMP, LFTs, TSH, B12, vitamin D, UDS; neuroimaging if CNS pathology suspected; EEG if atypical/seizure suspicion. Always do a suicide risk assessment.

Match the antidepressant's side effect to the medical context

Agent	Useful when…	Watch
SSRIs	Comorbid anxiety/PTSD; IBS-constipation subtype	GI bleed, QTc (citalopram), SIADH in elderly
SNRIs (duloxetine, venlafaxine)	Neuropathic / musculoskeletal pain	HTN (venlafaxine), hepatotoxicity (duloxetine)
Bupropion	Fatigue, low motivation, weight loss, sexual dysfunction, comorbid ADHD	Avoid with seizures / brain injury; lowers threshold
Mirtazapine	Cachexia/poor appetite, insomnia, nausea	Weight gain, sedation
TCAs	Chronic pain, IBS-diarrhea subtype, migraine prophylaxis	Anticholinergic, arrhythmia, orthostasis
Stimulants (methylphenidate)	Fast-acting in HIV/cancer/hospitalized with short time-frame; fatigue	Tachycardia, weight loss

Beyond drugs: psychoeducation and a supportive relationship (instill hope, protect self-esteem, counter nihilism) frame all care; behavioral activation for mild cases; evidence-based psychotherapies (CBT, IPT, short-term psychodynamic, MBCT). ECT for precarious function, treatment resistance, pregnancy, psychotic depression, catatonia, or Parkinson's depression. The collaborative care model integrates treatment with the medical team. Source: ACLP "How-To Guide: Depression in Medical Settings" (Lavakumar; rev. 2025).

Anxiety in the Medically Ill Consult-Liaison

In the medically complex patient, determining the cause is step one — anxiety may be a primary disorder, a direct effect of a general medical condition (GMC), a medication/substance effect, or a psychological reaction to illness. The formulation drives the treatment.

Four sources to differentiate

Primary anxiety / mental illness — pre-existing disorder
Effect of a GMC — has a physiological pathway (see below)
Substance/medication effect — prescribed drugs, illicit use, or withdrawal
Psychological reaction to the experience of illness

Medical conditions that mimic anxiety

Endocrine: hyperthyroidism, pheochromocytoma, hypoglycemia, hyperadrenalism, adrenergic overactivity
Cardiovascular: heart failure, arrhythmias
Respiratory: COPD, asthma
Neurological: Parkinson's, epilepsy, CNS neoplasm, vestibular dysfunction, encephalitis
Other: carcinoid

Psychological themes of the reaction to illness: uncertainty in diagnosis/treatment, uncertainty in prognosis, impact on identity & livelihood, changes to the body, fear of death, the hospital/strangers, and reactions of physicians and others. Naming the theme guides the psychotherapeutic response.

Medication mantra: start low, go slow

Short-term bridge: benzodiazepine, alpha-2 agonist, beta-blocker, antipsychotic, antihistamine. Long-term: SSRI ± mood stabilizer.

First-line antidepressants

Drug	Dose	Note
Sertraline	25–200 mg	SADHART — safe post-MI
Escitalopram	5–20 mg	Monitor QTc
Citalopram	10–40 mg	Monitor QTc (≤20 if elderly)
Fluoxetine	10–80 mg	2D6 inhibitor; long t½
Venlafaxine	37.5–225 mg	Serotonin discontinuation
Duloxetine	20–60 mg	Also treats neuropathy
Mirtazapine	7.5–45 mg	↑ appetite/sleep — useful in cachexia/insomnia

Short-term & adjunct options

Drug	Dose	Note
Lorazepam	0.25–2 mg BID–QID	No 1st-pass / glucuronidated — best in liver disease
Clonazepam	0.25–1 mg BID–TID	Longer half-life
Buspirone	5–20 mg BID–TID	Effective in 2–4 wk; no abuse potential
Hydroxyzine	25–50 mg BID–TID	Antihistamine; watch anticholinergic load
Propranolol	10–20 mg BID–TID	Avoid in COPD/asthma
Gabapentin	100–300 mg TID	Helpful in alcohol use
Quetiapine / aripiprazole (off-label)	Quet 12.5–25; arip 2–10 mg	Arip = less QTc; ziprasidone = most QTc

Treatment selection is driven by the timeline (short- vs long-term) and the formulation. CBT is effective across all anxiety disorders (large RCTs); IOP/DBT levels of care help complicated cases; mind-body interventions (yoga, mindfulness) have small-effect evidence. Be aware of racial/ethnic disparities in anxiety detection and treatment — they can be reduced with deliberate clinical attention. Source: Brandstetter, "Anxiety Management in Medically Complex Patients" / "Advanced Management of Anxiety," 2024–25; Roy-Byrne 2008; Bandelow 2017.

Practical tactics: ~50% of GAD patients fail the first SSRI — set expectations and have a switch/augment plan. When using benzodiazepines, limit risk with short courses, partial/incremental supplies, and a defined taper. Prioritize comorbidity treatment in order: substance use → psychosis → mood → anxiety → ADHD. Warn patients meds may transiently worsen anxiety before improving. Source: Hunt, "Anxiety Disorder Medication Management," 2020.

Demoralization vs Depression Consult-Liaison

Demoralization is distress + subjective incompetence — existential despair, hopelessness, helplessness, and loss of meaning/purpose. It is a treatable condition that can occur without any psychiatric comorbidity, and it is common in cancer and progressive illness (prevalence ~13–18%).

Distinguishing it from depression

Demoralization: the problem is perceived future incompetence ("I won't be able to…"); affect has a reactive range — the patient brightens when friends visit; anticipatory anhedonia ("can't" rather than "don't want to")
Depression: pervasive anhedonia & ↓ motivation ("I don't want to and it won't be fun anyway"); restricted affect regardless of situation (turns away, pulls sheets up)
They can coexist — if a depressive disorder is present it still warrants treatment

Severity continuum & correlates

Mild = loss of confidence → moderate = losing hope → severe = "all hope is lost"
Oncology risk factors: living alone, single, younger, female, high symptom burden, fatigue, restricted mobility, constipation, depression/anxiety, lack of life purpose, desire for hastened death
Protective: being employed. No association with cancer stage/type/site or time since dx
Assessed with the Demoralization Scale (24-item) or DCPR

Approach: DSM-5 has no specific diagnosis — use a dimensional approach. For moderate symptoms (or those from inadequate coping), use demoralization as a specifier for adjustment disorder; for severe demoralization, evaluate separately and screen comorbid disorders. Treatment is primarily psychotherapy aimed at improving coping, restoring meaning, and lifting morale; add antidepressants for severe demoralization or comorbid depression, and aggressively treat physical symptom burden. Source: ACLP "How-To Guide: Demoralization" (Chopra; Soeprono & Zein, 2024).

Suicide Risk in the General Hospital Consult-Liaison

Scope: Structured assessment and disposition on the medical/surgical service (C-L consult). General suicide/violence risk framework → Assessment → Risk Assessment.

A structured assessment weighs risk and protective factors — prioritizing modifiable targets — and documents reasoning, not just a "low/high" label. The goal is to stratify acute risk and lower it, not to predict suicide accurately. The transition from ideation to attempt is driven by conditions that increase distress (panic, PTSD) or decrease restraint (substance use, cluster-B impulsivity).

Screening vs full assessment

Screening (C-SSRS Screener, ASQ, PHQ-9 Item 9): any trained clinician using a validated tool
Full suicide risk assessment: requires formal training in structured suicide risk evaluation — ideation ladder, intent/plan/means, preparatory behaviors, collateral, acute vs chronic risk
If you lack formal training: do not independently assign final risk level or disposition after a positive screen, unclear risk, or moderate/high C-SSRS category. Obtain emergency psychiatry evaluation — consult or in-person ED evaluation by a psychiatrist (or equivalently trained clinician per local policy)

Risk factors

Non-modifiable: male sex (completion), older age, white race, family history of suicide, prior attempts (severity > number; 2nd attempt often within 3 months), early-life adversity
Modifiable: depression/psychosis, hopelessness, substance misuse/intoxication, insomnia, pain, social isolation, financial/housing stress, access to lethal means, recent loss
Medical: delirium, dementia, HIV, cancer, MS, Huntington's, ESRD, spinal cord injury, chronic pain (medical illness linked to 35–40% of suicides)
90% who die have a psychiatric diagnosis; 30–60% an SUD; 25–50% intoxicated at death

Assessment & protective factors

Ask directly & nonjudgmentally; elicit plan, intent, means, preparatory acts, rehearsal, and rescue/lethality (knowledge of lethality, steps to avoid discovery). Corroborate with collateral
Protective: restricted access to means, problem-solving skills, cultural/religious prohibition, social support, reasons for living, dependent children
Screen in the ED: ~1 in 5 who die visited an ED within 4 weeks; ~half who screen positive don't volunteer ideation

Disposition (by structured risk level)

Low → outpatient plan + Stanley-Brown safety plan + lethal-means counseling + crisis resources + follow-up within 7 days
Moderate → safety plan + means restriction; consider PHP/IOP; follow-up 48–72 h; psychiatric evaluation before discharge unless formally trained assessor documents safe disposition
High → do not discharge without psychiatric evaluation: inpatient, crisis stabilization, or ED observation; consider 1:1 if imminent risk

Management: stabilize the medical condition; treat the psychiatric syndrome; remove dangerous objects, 1:1/sitter, serial reassessment; address modifiable medical/social factors; clear documentation and a safe discharge plan. Content reflects published guidelines — apply with clinical judgment and institutional protocol. Source: ACLP "How-To Guide: Suicide Risk Assessment" (Sotelo, 2022); VA/DoD Suicide Risk CPG (2024).

Psycho-Oncology & Palliative Care Consult-Liaison

Psychiatric care across the cancer trajectory; high rates of distress, depression, anxiety, and delirium.

Common issues & pearls

Screen with the Distress Thermometer; distinguish adjustment, major depression, and demoralization (see those sections)
Use an inclusive (symptom-counting) approach — somatic symptoms overlap with cancer/treatment
Psychostimulants (methylphenidate) — rapid onset for depression/fatigue when prognosis is short; also opioid-related sedation
Delirium is the most common neuropsychiatric complication of advanced illness (often reversible early; terminal late)

Treatment-related & medication notes

Corticosteroids → mania/psychosis/depression/insomnia; interferon, some chemo → depression
Ondansetron, methadone → QTc; watch serotonergic combinations (linezolid, fentanyl) → serotonin syndrome
Mirtazapine (appetite/nausea/sleep), duloxetine (neuropathic pain) — choose the antidepressant by symptom benefit
Meaning-centered / dignity therapy; manage anticipatory grief; coordinate with palliative care

APA/ACLP psycho-oncology & palliative references.

Death & Dying on the Consult Service Consult-Liaison

"To cure sometimes, to relieve often, to comfort always." The goal at end of life is not to solve problems but to synthesize and validate the patient's narrative, preserve dignity, and treat genuine psychiatric comorbidity.

Setting & the conversation

Ensure privacy; sit at eye level; establish who the patient wants present
Ask who they are first, then their understanding of their condition, then how much they want to know
Use plain words — "death," "dying" — avoid euphemisms; stop often to validate and summarize
Reframe hope with "I wish…" statements; most end-of-life conflicts are about values, not facts

Frameworks for the psychological state

Kübler-Ross stages (not universal or sequential): denial, anger, bargaining, depression, acceptance
Erikson — dying patients are often thrust into integrity vs despair regardless of age
Spiritual assessment — meaning, connectedness; refer to chaplaincy; avoid premature reassurance and theological debate

Psychiatric comorbidity at end of life

Disorder	Screen	Pearls / treatment
Anxiety	GAD-7, STAI, Fear of Disease Progression	Distinguish pre-existing vs adjustment vs disease/treatment-related; address fears of death/separation/finances; midazolam/morphine help terminal dyspnea/restlessness
Depression	HADS, PHQ-2	Don't assume depression is "normal" dying — nor pathologize grief. Anhedonia, low self-esteem, hopelessness favor depression over grief. Psychostimulants (methylphenidate) act fast in a short time-frame
Delirium (hypo/hyper/mixed)	CAM, MoCA, MMSE	Most common neuropsych complication in advanced illness (19–58%); often reversible. Haloperidol (can give SC); risperidone/olanzapine; benzos or midazolam/propofol for refractory terminal delirium

Dignity & meaning therapies: Dignity Therapy uses life-review questions ("Tell me about your life… When did you feel most alive?… What would you want your family to remember?"). Meaning-centered therapy draws on historical, attitudinal, creative, and experiential sources of meaning. The most important factor is staying with the patient so they don't feel abandoned. Finally — practice self-care; it's okay to grieve. Source: ACLP "How-To Guide: Death and Dying" (Chang & Mihalik-Wenger, 2023).

Transplant Psychiatric Evaluation Consult-Liaison

The pre-transplant psychiatric evaluation determines whether psychiatric/psychological factors will interfere with coping and adherence. The psychiatrist's goal is to enhance candidacy where possible — not simply to act as gatekeeper.

The evaluation = diagnostic interview + 4 extras

Standard psychiatric diagnostic interview, plus: capacity, adherence/coping, care-support, and understanding of the transplant process (largely educational)
Adherence — past behavior predicts future; AMA history, no-shows, and missed meds are red flags. Lifelong immunosuppression is non-negotiable
Care-support — 24/7 support is required; lack of adequate care support is a contraindication
Verify housing near center, transport, finances/insurance
Standardized tool: SIPAT
Most programs require ~6 months abstinence from alcohol/substances before listing

Substance use & process

Detailed SUD history (first/last/heaviest/most-recent use, abstinence periods), treatment history, insight into triggers and a relapse-prevention plan, sober supports/housing
Clarify urgency — acute organ failure may require a decision within hours vs. more time for chronic exacerbations
Educate that transplant is an extreme stressor that can precipitate psychiatric illness — build contingency plans
Report to the committee as risk tier or list/not-list per center; state diagnosis, stage (remission vs acute), refractoriness, and the patient's strengths

Frame it constructively: rather than "weeding out" candidates, recommend the addictions treatment, therapy, neuropsych testing, or care-coordination that would make a borderline candidate listable. Psychiatry is one part of a multidisciplinary committee reviewing high data volume — stay focused and practical. Source: ACLP "How-To Guide: Transplantation" (Soeprono & Zimbrean, 2020).

Psychopharmacology after Bariatric Surgery Consult-Liaison

Bariatric surgery alters drug absorption and metabolism. The CL psychiatrist anticipates these changes, gets a pre-op baseline, and adjusts deliberately — the one agreed proactive step is switching extended-release to immediate-release where possible.

Procedures & PK changes

Restrictive (band, sleeve): smaller pouch impedes pills >10 mm; strict early caloric limits
Malabsorptive / combined (Roux-en-Y, BPD-DS): ↓ intestinal absorption; bypass of proximal small bowel removes CYP3A4 → potentially higher levels of 3A4 substrates (aripiprazole, buspirone, carbamazepine, citalopram, mirtazapine, quetiapine, trazodone, vilazodone)
Faster gastric emptying → incomplete tablet dissolution; weight loss → smaller Vd for lipophilic drugs, improved hepatic/renal clearance
Caloric absorption traps: ziprasidone (500 kcal) & lurasidone (350 kcal) — at ~250 kcal ziprasidone absorption ↓ up to 90%
Smoking cessation pre-op induces-then-releases → ↑ clozapine/olanzapine/clomipramine levels; lithium is vulnerable to perioperative fluid shifts

Action steps by phase

Pre-op: baseline MSE + rating scales ± plasma levels; switch ER/enteric → IR; otherwise don't change a stable regimen
0–12 mo: distinguish withdrawal vs recurrence vs side effect; trend levels/scales. For malabsorption: IR → ↑/divide dose → crush/ODT/liquid → alternate route ("bypass the bypass": transdermal, IM, SL, PR) → switch agent. For toxicity (3A4/1A2 substrate): ↓dose, check labs
>1 yr: homeostasis recovers (hepatic CYP compensates; smoking may resume) — consider retrial of the pre-op regimen; watch new-onset alcohol use disorder (~7–8%)

Source: ACLP "How-To Guide: Psychopharmacology after Bariatric Surgery" (Fipps, 2021).

Behavioral Plans in the Medical Setting Consult-Liaison

A structured plan helps when behavior disrupts care — agitation/aggression, excessive dependence, noncompliance, boundary violations, surreptitious behaviors, or staff conflict driven by personality pathology. The key move is to identify the function (driver) of the behavior and intervene on it.

Common drivers → targeted interventions

Driver / function	Sample intervention
Attention-seeking	Reinforce desired behavior with attention; withdraw reinforcement from unwanted behavior (caregiver leaves briefly, states when returning + the expected change)
Stimulation / anxiety	Address boredom (music, activities, comfort objects), regular exercise, safety barriers for wandering
Escape / avoidance	Pause the interaction, state a specific return time; distract an agitated patient and re-attempt
Autonomy / power struggle	Offer real choices ("dressing before or after lunch?"); break tasks into smaller steps
Confusion	Reorient (labels, calendar), restore day-night cycle, out of bed during day

Personality-cluster responses

Cluster A (paranoid/schizoid/schizotypal): ignore non-interfering behaviors; convey care through information & respect for autonomy, not an overly warm style; assess capacity if refusing care
Cluster B (antisocial/borderline/histrionic/narcissistic): reinforce desired behavior, ignore minor negatives; label the behavior (not the person) and ask it to stop; manage staff countertransference & splitting; decide which limits are firm vs flexible
Cluster C (avoidant/dependent/OCPD): scheduled, predictable brief check-ins not contingent on requests; have the patient bundle requests; treat underlying anxiety; set limits with a planned daily time for questions

Build & disseminate the plan: interventions should be practical, ethical, and time-limited, with input from the medical team, nursing, and (when able) the patient. A written plan documents the problem behaviors, contributing factors, expectations the patient can meet, staff response options, behavioral goals/outcome measures, and a re-evaluation timeline. Use a verbal plan when a written one would stigmatize. Expect some behaviors to worsen transiently before consistency pays off. Source: ACLP "How-To Guide: Behavior Plans" (Felde; updated 2024).

Special Populations

Age, sex, and medical-population-specific psychiatry

Child & Adolescent

Geriatric

Women's & Perinatal

HIV Psychopharmacology

Identity, Culture & Forensic

Child & Adolescent Psychiatry Special Population

Diagnosis is developmentally framed and relies on multiple informants (child, parent, school). Prescribe conservatively; psychotherapy/parent-management is often first-line.

High-yield pharmacology points

Antidepressant black-box warning (↑ suicidal ideation, age <25) — monitor closely; fluoxetine & escitalopram are FDA-approved for adolescent depression (fluoxetine for ages ≥8)
ADHD: stimulants first-line (FDA from age 6); atomoxetine/guanfacine/clonidine alternatives
Autism irritability: risperidone & aripiprazole FDA-approved
Start low, monitor growth/weight/cardiac; involve family

Childhood-onset conditions

DMDD (chronic irritability + outbursts; ages 6–18) vs pediatric bipolar (episodic)
Separation anxiety, selective mutism, school refusal (CBT first-line)
Oppositional defiant / conduct disorder (parent-management training; conduct → antisocial PD risk)
Enuresis/encopresis; autism, ADHD, tics — see Neurodevelopmental
Maltreatment/RAD & disinhibited social engagement; always assess safety

AACAP practice parameters; DSM-5-TR.

Intellectual & Developmental Disability Special Population

DSM-5-TR intellectual disability = deficits in intellectual functioning (reasoning, problem-solving) AND adaptive functioning (conceptual/social/practical), with onset in the developmental period. Severity is graded by adaptive function, not IQ alone.

Diagnosis, severity & etiology

Severity (adaptive): mild (~85% — independent with support), moderate, severe, profound
Etiologies: genetic (Down syndrome, Fragile X — most common inherited; Prader-Willi, Williams), fetal alcohol spectrum (leading preventable cause), prenatal/perinatal injury, metabolic (PKU), infections, lead
Global developmental delay = <5 yo, not yet fully assessable
Distinguish from specific learning disorder (isolated domain) and autism (can co-occur)

Psychiatric comorbidity & assessment

Psychiatric illness is 3–4× more common than in the general population
Diagnostic overshadowing — attributing symptoms to the IDD and missing a treatable disorder; behavioral change is often the "presenting symptom" of pain, depression, psychosis, or a medical problem
Use collateral, baseline behavior, and behavioral analysis (ABC); rule out medical causes & pain first
Communicate at the developmental level; assess capacity decision-by-decision; involve guardians appropriately

Management: behavioral & environmental interventions first (functional analysis, skills, caregiver training). Medications target a specific comorbid disorder or symptom — not "behavior" generically; start low, go slow, watch paradoxical reactions & heightened side-effect sensitivity, avoid polypharmacy and chemical restraint, and review/deprescribe regularly. Risperidone/aripiprazole are FDA-approved for irritability/aggression in autism; treat underlying depression/anxiety/psychosis on their own merits. DSM-5-TR; AADMD/standard references.

Dementia — Cognitive & Behavioral Treatment Geriatric

Cognitive enhancers

Drug	Class / stage	Notes
Donepezil	Cholinesterase inhibitor; all stages (5→10, 23 mg)	Modest symptomatic benefit; metabolized by 2D6/3A4
Rivastigmine	AChE + butyrylcholinesterase inhibitor; oral or patch	Also approved for Parkinson's disease dementia; patch reduces GI effects
Galantamine	AChE inhibitor + nicotinic modulator; mild–moderate	—
Memantine	NMDA antagonist; moderate–severe	Well tolerated; can combine with a cholinesterase inhibitor

Cholinesterase inhibitor side effects: nausea/diarrhea, anorexia, vivid dreams, bradycardia/syncope (caution with conduction disease). Benefits are modest/symptomatic, not disease-modifying.

Behavioral & psychological symptoms of dementia (BPSD)

>80% develop agitation during the course; psychosis ~50%. Identify and treat reversible contributors first: pain (stepwise analgesia significantly reduces agitation), sleep disruption / RLS, delirium (incl. hypoactive), psychosis, medication effects, sensory impairment, unmet needs.

Non-pharmacological first-line — DICE: Describe the behavior, Investigate contributors, Create a plan, Evaluate. Medications only when non-pharm fails or there's danger.

Stepwise algorithm — behavior problem in dementia

1Rule out & treat reversible causes

Evaluate/manage delirium, pain, other medical, and environmental causes for the behavior

↓

define the target

2Characterize the behavior

Specify it concretely — "screaming," "hitting when bathed" > vague "agitation"
Identify what brings it on and what makes it go away
Identify whom it bothers (patient? caregiver/staff? other patients?)

↓

first-line

3Nonpharmacologic management + educate caregivers

Directed at the specific behavior. Improved → monitor for recurrence.

↓

not improved

4Depression or anxiety symptoms?

Yes → trial of an SSRI (e.g., citalopram ≤20 mg / sertraline)
No → on a cholinesterase inhibitor? If not → trial ChEI ± memantine → if improved, monitor for recurrence & adverse events

↓

behavior persists

5Trial of atypical antipsychotic

Risperidone 0.25–2 mg (best evidence), olanzapine, aripiprazole, quetiapine (PD/Lewy body)
Improved → monitor for EPS/sedation; attempt taper every 6 months (BBW: ↑ mortality)

↓

not improved

6Trial of an SSRI

If not already tried (CitAD: citalopram ≈ risperidone, better tolerated; cap 20 mg)

↓

not improved

7Carbamazepine / specialist referral

Consider a trial of carbamazepine; recommend referral to a specialist

Antipsychotic BBW (2005 atypicals, extended to typicals 2008): increased mortality in elderly dementia patients (~1.6–1.7× placebo; ~4.5% vs 2.6% over ~10 wk) — cardiovascular and infectious deaths; plus ↑ cerebrovascular events (~1.3–2×). Beers criteria: avoid antipsychotics for BPSD unless non-drug options fail and patient is a danger to self/others.

If medication is necessary — evidence summary

Risperidone (0.25–2 mg) — best evidence, modest benefit for aggression/psychosis short-term; ↑prolactin, CVAE
Olanzapine (1.25–10 mg) — some benefit for agitation/aggression
Aripiprazole — inconclusive; Quetiapine — minimal benefit but well tolerated (used in Parkinson's/Lewy body)
Haloperidol — benefit for aggression (not general agitation); EPS, QTc
Citalopram (CitAD trial) — benefit for agitation, comparable to risperidone with better tolerability; cap at 20 mg (QTc >30 mg)
Cholinesterase inhibitors, memantine, trazodone, buspirone, anticonvulsants (valproate) — inconclusive/not proven for agitation
Dextromethorphan–quinidine — emerging evidence for agitation (↑falls)
Avoid benzodiazepines (or very short-term only)

CATIE-AD: adverse effects offset efficacy of SGAs for agitation/psychosis/aggression in AD. Psychosis itself (not the drug) predicts nursing-home admission and death.

Prescribing in the Elderly Geriatric

Adverse drug reactions are 7–10× more frequent at age 70–79 than 20–29; ~20% of admissions over 70 are ADR-related. Psychoactive drugs and anticoagulants are the most common culprits. The elderly are 13% of the population but 40% of prescriptions.

Pharmacokinetic changes

↑ volume of distribution (more adipose) → longer half-life of lipophilic drugs (benzodiazepines accumulate)
↓ GFR / renal clearance → adjust renally-cleared drugs (lithium, paliperidone, gabapentin, desvenlafaxine)
↓ hepatic blood flow & mass; ↓ total body water & plasma volume
75% of ADRs are dose-related → "start low, go slow"

Anticholinergic burden

Leading cause of delirium in the elderly
effects of multiple mildly anticholinergic drugs are cumulative
Potent offenders: amitriptyline (& tertiary TCAs), diphenhydramine/hydroxyzine, clozapine/olanzapine, oxybutynin, benztropine, paroxetine
Also worsens cognition and constipation/retention

High-yield interaction & safety pearls

Citalopram max 20 mg if >60 yo, hepatic impairment, 2C19 poor metabolizer, or on cimetidine (QTc/torsades)
SSRIs + warfarin/NSAIDs/antiplatelets → ↑ GI bleeding (SSRIs impair platelet aggregation); excess bleed 3–12/1000 tx-yrs, higher with prior bleed/age >80
AMDA "top-10" interaction: warfarin + NSAIDs, macrolides, phenytoin, sulfas, quinolones
2D6 poor metabolizers (~7% Caucasian): ↓ codeine/tramadol activation; ↑ risk from 2D6 substrates; tamoxifen needs 2D6
2C19 poor metabolizers (~13% Asian, 3% Caucasian): ↓ clopidogrel activation; ↑ citalopram/escitalopram/diazepam exposure
Beers criteria: avoid benzodiazepines, strongly anticholinergic agents, and antipsychotics-for-BPSD in older adults where possible

When to worry about an interaction: multiple co-administered drugs, narrow-therapeutic-index "victim," and a potent inducer/inhibitor. Reassess whenever the clinical picture unexpectedly changes — and remember herbals (St John's Wort induces 3A4 + P-glycoprotein → ↓ digoxin, statins, antiretrovirals).

Beers Criteria — Psychotropics Geriatric

AGS Beers Criteria list potentially inappropriate medications (PIMs) in adults ≥65 — drugs whose risks usually outweigh benefits and for which safer alternatives exist. The psychotropic PIMs:

Drug / class	Concern	Recommendation
Benzodiazepines (all)	↑ cognitive impairment, delirium, falls, fractures, MVAs; older adults are more sensitive & metabolize slower	Avoid (exceptions: seizure, severe GAD, alcohol/benzo withdrawal, periprocedural)
"Z-drugs" (zolpidem, zaleplon, eszopiclone)	Same harms as benzodiazepines — delirium, falls, fractures, ED visits	Avoid
Antipsychotics (1st- & 2nd-gen)	↑ stroke & mortality in dementia; falls; anticholinergic/metabolic	Avoid for BPSD or insomnia unless non-drug options failed and patient is a danger; avoid in delirium (except schizophrenia, bipolar, short-term antiemetic)
Tertiary TCAs (amitriptyline, imipramine, clomipramine, doxepin >6 mg, trimipramine)	Strongly anticholinergic, sedating, orthostasis	Avoid
Paroxetine	Most anticholinergic & sedating SSRI	Avoid
First-generation antihistamines (diphenhydramine, hydroxyzine, chlorpheniramine, doxylamine)	Highly anticholinergic → confusion, dry mouth, constipation, delirium; tolerance to hypnotic effect	Avoid
Chronic anticholinergics (benztropine, trihexyphenidyl, oxybutynin)	Cognitive impairment; not for routine prophylaxis of EPS	Avoid for behavioral control / chronic use
Barbiturates, meprobamate	High dependence, tolerance, overdose risk	Avoid

Drug–disease interactions

Dementia / cognitive impairment: avoid anticholinergics, benzodiazepines, Z-drugs, antipsychotics (chronic/PRN unless danger)
Delirium: avoid anticholinergics, benzodiazepines, antipsychotics (can prolong), corticosteroids, H₂-blockers, meperidine
Falls / fractures (or history): avoid antiepileptics, antipsychotics, benzodiazepines, Z-drugs, TCAs/SSRIs, opioids

Drug–drug interactions

≥3 CNS-active drugs (antipsychotic, benzo, Z-drug, TCA, SSRI/SNRI, opioid, gabapentinoid, antiepileptic) → avoid — falls/fractures
Two+ anticholinergics → avoid (cumulative burden)
Lithium + loop diuretic / ACE-I / ARB → ↑ lithium toxicity → avoid or monitor closely
Anticholinergic + cholinesterase inhibitor → opposing actions → avoid

Use with caution (hyponatremia/SIADH): SSRIs, SNRIs, TCAs, mirtazapine, antipsychotics, and carbamazepine can cause/worsen hyponatremia — monitor sodium, especially at initiation or dose increase. Source: AGS Beers Criteria (2023 update).

Perinatal Psychiatry Women's MH

Women are ~2× as likely as men to have mood disorders. Always weigh risk of medication vs. risk of untreated illness — untreated antenatal depression raises risk of preterm birth, low birth weight, breastfeeding problems, and postpartum depression.

Antidepressants in pregnancy

Congenital malformation: most studies show no overall increased risk. Paroxetine is the exception historically linked to cardiac defects (now avoided; was relabeled Category D); newer analyses suggest the signal may partly reflect detection bias.
Persistent pulmonary hypertension of the newborn (PPHN): rare baseline (~1/1000); some (not all) studies link to SSRIs.
Neonatal adaptation syndrome: <30% of third-trimester–exposed infants — respiratory distress, autonomic instability, poor feeding, tremor/myoclonus/rarely seizures. Self-limited, supportive care.
Neurobehavioral follow-up: largely reassuring (IQ/Bayley similar to controls); maternal depression itself worsens child outcomes.
Most SSRIs (except paroxetine), bupropion, venlafaxine, trazodone, and TCAs are Category C. Avoid switching agents during pregnancy without prior response history.

Postpartum mood disorders

Disorder	Incidence	Presentation	Treatment
Postpartum blues	26–85%	80% resolve by week 2; 20% evolve to PPD	Support/reassurance
Postpartum depression	10–20%	Onset 1st month; often with anxiety/obsessions; marital problems → treatment-resistant	Antidepressant + psychotherapy (IPT, CBT)
Postpartum psychosis	0.2%	Onset by ~day 3; mixed/rapid cycling; risk of infanticide; often bipolar	Hospitalize; antipsychotics, mood stabilizers, benzos, ECT

Always check thyroid (postpartum thyroiditis), anemia, B12/folate. Sertraline more effective than placebo for PPD prophylaxis in women with prior PPD.

Perinatal psychopharmacology — agent guidance (C-L)

SSRIs/SNRIs: generally safe; no clear teratogenicity or neurodevelopmental harm vs children of non-ill mothers. ~30% non-dose-dependent neonatal adaptation syndrome (manage with swaddling/skin-to-skin/frequent feeds — do not lower/stop the dose pre-delivery). <10% breastmilk transfer for all SSRIs
Antipsychotics: atypicals — malformation rate ~1.4% vs 1.1% (no specific agent favored); haloperidol acceptable if stable/needed
Lithium: small absolute Ebstein/RVOT risk — maintainable through pregnancy. Levels trough in the 2nd trimester → may need dose ↑; split BID to avoid peaks; weekly levels from week 34 until 2 wk postpartum; at delivery return to pre-pregnancy dose or drop to ⅔ of pre-delivery dose; check infant level if breastfeeding
Valproate: first-trimester malformation 6.1% (neural tube defects) + autism/neurodevelopmental risk — avoid in any reproductive-age woman without reliable long-acting contraception; discontinue when pregnancy diagnosed
Lamotrigine: well-tolerated and effective; early cleft-lip signal not replicated
Benzodiazepines: limit to 2–3 PRN doses/week, lowest dose (preterm labor, low birth weight, floppy-baby/respiratory depression). Stimulants: lowest effective dose/frequency, drug holidays when feasible

Special considerations: ask all reproductive-age women about pregnancy plans in the next 12 months. Bipolar disorder usually warrants continued pharmacotherapy (strong untreated-BD → postpartum-psychosis link); breastfeeding disrupts sleep → mania risk. For agitation requiring restraint, use left-lateral position (avoid IVC compression; pregnancy is hypercoagulable → DVT risk). Alcohol/opioid withdrawal are life-threatening to mother and fetus — treat to standard; buprenorphine → less neonatal abstinence than methadone. Source: ACLP "How-To Guide: Perinatal Mental Health" (Slocum, 2021).

Breastfeeding: all psychotropics enter breast milk. Use lowest effective dose; AAP target Relative Infant Dose <10% (most antidepressants qualify). Sertraline is preferred — several studies show undetectable infant serum levels. Fluoxetine & citalopram → higher infant levels (rare irritability/poor feeding). CYP450 immature until ~2 months (caution in premature infants).

Screening & public-health priorities (APA/CDC)

Suicide and overdose are leading causes of death in the year after delivery — perinatal mental health is a mortality issue, not just morbidity
Universally screen all women of childbearing age for both mental and substance use disorders; treat perinatal mood/anxiety disorders (PMADs) as a standard perinatal risk factor
Validated tools: EPDS (Edinburgh Postnatal Depression Scale) or PHQ-9 for depression; AUDIT-C / 4Ps for substance use — repeat across pregnancy and postpartum, not once
Large treatment gap: ~75% of affected pregnant persons go untreated; only ~⅓ with OUD receive methadone/buprenorphine despite proven safety

Disparities & protective factors

Racial/ethnic disparities in both screening and treatment access — Black, Indigenous, rural, and low-income birthing people are under-screened and under-treated
Stigma & fear of legal/child-welfare consequences delay care; the APA/CDC paper advocates non-criminalizing, family-focused policy
Breastfeeding is protective: exclusive breastfeeding is linked to ~53% lower postpartum-depression risk (overall breastfeeding ~14% lower) — support, don't pressure
Adolescent pregnancy carries elevated later suicide risk → heightened screening

Source: APA & CDC, Perinatal Mental and Substance Use Disorders white paper, 2023.

Premenstrual Dysphoric Disorder (PMDD) Women's MH

Diagnosis

≥5 symptoms (≥1 core) in the week before menses, remitting within days of onset: markedly depressed mood*, marked anxiety/tension*, affective lability*, persistent anger/irritability*, ↓interest, ↓concentration, feeling overwhelmed, sleep change, lethargy, physical symptoms (breast tenderness, bloating). *core
Confirm prospectively over 2 cycles with daily rating forms

Distinct from depression: tied to cycle, resolves with menses, pregnancy resolves it
Hardest differential = bipolar, rapid-cycling
Rule out thyroid disease, hyperprolactinemia

Treatment

SSRIs — all effective; rapid onset (1–2 days). Luteal-phase-only dosing is effective and often first choice.
SNRIs — limited evidence of efficacy.
Yaz / Yasmin (drospirenone + ethinylestradiol) OCPs improve PMDD.
GnRH agonists (ovulation suppression) effective in 50–70% of "pure" PMDD.
Augment residual anxiety with gabapentin, benzodiazepine, or buspirone.
Lifestyle: calcium 1200 mg/day, exercise, limit caffeine/alcohol.

Bipolar Disorder & Pregnancy Women's MH

High postpartum risk: bipolar women have a ~100× higher risk of postpartum psychosis than women without psychiatric history; ~⅔ experience a postpartum mood episode within a month of delivery. Lithium prophylaxis (restarted in acute postpartum or 2nd–3rd trimester) reduces relapse.

Mood stabilizers in pregnancy

Agent	Teratogenic risk	Notes
Lithium	Ebstein anomaly — reanalyzed at ~1–2/1000 (20–40× baseline but low absolute); cardiac risk = 1st-trimester exposure	Monitor levels (umbilical = maternal); hold dose ~24–48 h before delivery to avoid neonatal toxicity
Valproate	Major malformations 6–20%; neural tube defects 5–9%; ↓IQ	Switch before conception if possible
Carbamazepine	Malformations 2–8%; craniofacial 11%, NTD, low birth weight	Avoid; supplement vitamin K
Lamotrigine	Dose-related: 1.3% (<100 mg) → 5.4% (>200 mg); cleft lip/palate signal	Relatively preferred; cleared for use in pregnancy
1st-gen antipsychotics	No clear ↑ malformation	Transient neonatal EPS/withdrawal
2nd-gen antipsychotics	Limited data; olanzapine → weight gain, gestational DM, preeclampsia	Monitor weight, glucose, BP

Teratogenicity timetable: CNS/neural tube days 10–32; cardiac (Ebstein) days 20–56; lip/palate days 42–63. Management: preconception counseling ≥3 months ahead; avoid meds in 1st trimester if feasible; monotherapy at minimum effective dose; folic acid 400 mcg (3–4 mg if on a mood stabilizer).

Teratogens (Psych-Relevant) Pregnancy

Agent	Effect on fetus	Notes
Lithium	Ebstein anomaly (apical displacement of tricuspid valve)	Avoid 1st trimester
Antiepileptics (valproate, carbamazepine, phenytoin, phenobarbital)	Neural tube defects, cardiac defects, cleft palate, skeletal abnormalities	High-dose folate recommended; valproate worst
Benzodiazepines	(General caution) — neonatal sedation/withdrawal	—
Alcohol	Fetal alcohol syndrome — common cause of birth defects & intellectual disability	—
Cocaine	Low birth weight, preterm, IUGR, placental abruption	Vasoconstriction
Smoking (nicotine, CO)	Low birth weight (leading cause), preterm, IUGR, SIDS, ADHD	Vasoconstriction; ↓O₂ delivery

Most susceptible 3rd–8th weeks (organogenesis). Source: First Aid teratogens table. Lamotrigine relatively preferred mood stabilizer in pregnancy (per notes); lurasidone the only antipsychotic historically labeled Pregnancy Category B.

HIV & the Brain HIV

CD4 count & CNS implications

>500: acute retroviral syndrome, aseptic meningitis, HAND
200–500: Kaposi's sarcoma, B-cell lymphoma
<200: PCP pneumonia, PML, HIV-associated dementia, neuropathy, NHL
<100: toxoplasmosis, cryptococcosis
<50: CMV, MAC, CNS lymphoma

HIV enters CNS early via monocytes; chronic inflammation → neuropsychiatric change. Low CD4 nadir predicts neurocognitive impairment.

HIV-Associated Neurocognitive Disorders (HAND)

Spectrum: ANI (asymptomatic) → MND (mild) → HAD (dementia). Diagnosed by neuropsych testing + functional assessment + ruling out other causes. Seven domains: processing speed, learning, recall, executive function, verbal fluency, attention/working memory, motor.

Treatment: antiretroviral immune reconstitution is the mainstay. Higher CNS Penetration-Effectiveness (CPE) score → lower CSF viral load and lower HAND risk. Adjuncts studied: lithium (low-dose), stimulants (methylphenidate, dextroamphetamine for cognitive slowing), memantine (NMDA antagonist — safe but no clear benefit), paroxetine (cognitive benefit signal).

AIDS-defining CNS illnesses (differential for new neuro/psych change)

Illness	CD4	Incidence	Clinical / imaging
Toxoplasmosis	<100	2–4%	Intracranial mass — multiple ring-enhancing lesions (basal ganglia)
CMV encephalitis	<50	30–50%	Short-term memory loss → may progress to dementia
Cryptococcal meningitis	<100	8–10%	Fever, delirium, seizures without meningeal signs
PML (JC virus)	<100	~4%	Demyelinating, focal neuro signs; dx by MRI
CNS lymphoma	—	~0.32/1000	Single or multiple lesions on MRI; dx by brain biopsy

HAND categories & screening: Asymptomatic neurocognitive impairment ~33% · Mild neurocognitive disorder ~12% · HIV-associated dementia ~2%. Neurons are not directly infected — pathology is microglial nodules, multinucleated giant cells, white-matter demyelination; nigrostriatal/basal ganglia early, frontotemporal late. Screen if CD4 <350; HIV Dementia Scale cutoff 10/16; initial screen within 6 months of dx, then q6–12 mo (high risk) or q12–24 mo. Depression causes false positives.

ART Drug Interactions HIV

Most serious interactions involve CYP3A4; also glucuronidation (UGT), renal elimination, P-glycoprotein, alcohol dehydrogenase.

Worked examples (high yield)

Ritonavir (strong 3A4 inhibitor) + triazolam (3A4 substrate) → triazolam half-life 3.7 h → 50 h. Avoid.
Ritonavir induces 1A2; olanzapine is a 1A2 substrate → ↓olanzapine level (may need ↑ dose).
Ritonavir induces glucuronidation → ↓lorazepam level (may need ↑ dose).
Valproate inhibits glucuronidation + zidovudine (ZDV) → ↑ZDV → anemia. Consider lithium instead.
Modafinil (3A4 inducer) + ritonavir → ↓ritonavir → ↑viral load/resistance.
Efavirenz both induces and inhibits 3A4; can cause neuropsychiatric effects (nervousness, dizziness, depression, mania, psychosis, vivid dreams, suicidality).

Safest benzodiazepines with 3A4 inhibitors

Lorazepam, oxazepam, temazepam (glucuronidated, "LOT") — not elevated by 3A4 inhibitors. Alprazolam levels rise with potent 3A4 inhibitors → avoid.

Herbal cautions

St
John's Wort & garlic — CYP3A4/P-gp inducers → may reduce antiretroviral efficacy. Milk thistle — 3A4 inhibitor → ↑ART toxicity. Cat's claw → ↑protease inhibitor levels

Antipsychotic & antidepressant ART cautions (high yield)

Pimozide is contraindicated with antiretrovirals (3A4 → QTc/arrhythmia).
Lurasidone is contraindicated with protease inhibitors (strong 3A4 interactions).
Quetiapine + PI → ↑ quetiapine levels; aripiprazole ↑ with PIs, ↓ with NNRTIs (adjust dose).
Clozapine — use with caution and check levels (and ANC).
Saquinavir contraindicated with many phenothiazines, haloperidol, several TCAs, trazodone, paroxetine, sertraline, duloxetine. Indinavir contraindicated with alprazolam/diazepam.
3A4: inducers = efavirenz, nevirapine, rifampin, carbamazepine (↓ psych drug levels); inhibitors = ritonavir, indinavir, nelfinavir, fluvoxamine (↑ benzo/buspirone/citalopram/trazodone → sedation/respiratory depression).
2D6 inhibitors (ritonavir, nelfinavir; also bupropion/fluoxetine/paroxetine/duloxetine) → ↑ TCAs (cardiac conduction), neuroleptics, venlafaxine, mirtazapine.

Always check hiv-druginteractions.org before co-prescribing.

Psychiatric Management in HIV HIV

Symptom	Approach
Delirium	Medical workup; consider CNS workup if new symptoms & CD4 <200 (imaging, LP, metabolic/infectious/neoplastic)
Depression	Screen for bipolar first; select antidepressant by interaction/side-effect profile; consider stimulants; optimize ART
Agitation / mood lability	Prefer atypical antipsychotics (HIV affects basal ganglia → ↑EPS risk with typicals); watch metabolic effects; benzos with caution; lithium toxicity may occur rapidly
Anxiety	SSRIs, SNRIs, buspirone, mirtazapine; benzodiazepines with interaction caution
Insomnia / vivid dreams	Reassure (vivid dreams common with ART, e.g., efavirenz); sleep hygiene; choose hypnotic by etiology & interactions

Substance use in HIV: methamphetamine → neurocognitive harm and risky behaviors (protease inhibitors ↑ meth levels 3–10×); cocaine ↑ viral load; club drugs (ketamine, GHB, ecstasy) and opioids have dangerous ART interactions; alcohol accelerates liver disease.

Depression in HIV — treatment pearls

Prevalence 19–43%; bidirectional (MDD is a risk factor for HIV-exposing behavior; HIV raises MDD risk — depression rates 2.5× when CD4 <200 via subcortical injury)
Don't over-attribute somatic symptoms to HIV and miss MDD; high suicide risk
Antidepressant response 70–90%; stimulant response ~85% (also helps fatigue/cognitive slowing). Start low, go slow — more SE sensitivity, higher placebo rate
Match by symptom: avoid SSRIs with chronic diarrhea; avoid sedating agents with fatigue; avoid TCAs with oral candidiasis (anticholinergic dry mouth). Check testosterone (deficiency common)
St. John's Wort lowers protease-inhibitor levels — avoid. Psychotherapy targets guilt & stigma

Secondary mania & triple diagnosis

Secondary mania appears with CD4 <100 — always screen for AIDS-related CNS infection first
Lamotrigine = safe & effective; lithium → cognitive slowing, polyuria/dehydration; valproate → hepatotoxicity and ↑ZDV (zidovudine) → bone-marrow suppression; low-dose SGA to avoid EPS
"Triple diagnosis" = HIV + psychiatric disorder + substance use disorder. Methadone maintenance decreases HIV risk; rifampin ↑ methadone elimination → withdrawal
Personality & adherence: unstable extroverts (emotional instability, immediate-pleasure seeking) — antisocial/borderline most common; higher nonadherence and reactive medication-stopping

The single most important factor in HIV outcomes is medication adherence. Treatment-naïve regimens pair 2 NRTIs with an NNRTI, a ritonavir-boosted PI, or an INSTI (test resistance/genotype first). Source: Brandstetter, "Psychiatric Considerations in HIV," 2024; APA HIV guidelines.

LGBTQ+ & Gender-Affirming Care Special Population

Scope: Affirming care, minority stress, and population disparities. DSM criteria for gender dysphoria and paraphilic disorders → Disorders → Gender Dysphoria & Paraphilias.

Sexual orientation and gender identity are not disorders. Elevated psychiatric risk reflects minority stress, not the identity itself.

Minority-stress model & disparities

Distal stressors (discrimination, victimization, rejection) + proximal (internalized stigma, concealment, expectation of rejection) → ↑ depression, anxiety, PTSD, suicidality, and substance use
Transgender people have especially high suicide-attempt rates; LGBTQ youth are at high risk — family rejection is a major driver, family/school support is strongly protective
Disparities in access, insurance, and experiences of bias in healthcare worsen outcomes

Clinical approach

Use the patient's name & pronouns; ask, don't assume; separate orientation, gender identity, and behavior; protect confidentiality (esp. adolescents)
Gender dysphoria = the distress, not the identity (see that section); affirming care improves mental health
Gender-affirming care is multidisciplinary per WPATH standards (social, psychological, and — when indicated — hormonal/surgical); screen & treat comorbid illness
"Conversion therapy" is harmful and contraindicated. Watch interactions of gender-affirming hormones with psychotropics

APA & WPATH guidance; minority-stress model (Meyer).

WPATH SOC-8 (2022) — Gender-Affirming Care Evidence-Based

Standards of Care for the Health of Transgender and Gender Diverse People, Version 8. 18 chapters; framework shifted toward an informed-consent, individualized model with the mental-health professional as assessor/facilitator (not gatekeeper).

Criteria for adult gender-affirming medical/surgical care

Gender incongruence is marked and sustained
Meets diagnostic criteria for gender incongruence (where ICD framework applies) prior to intervention
Capacity to consent for the specific intervention
Other possible causes of apparent incongruence identified and excluded
Mental-health & physical conditions that could affect the outcome assessed, with risks/benefits discussed
Understands the effect on reproduction and has explored reproductive options
For surgery: additionally, stable on hormones if used (suggested ≥6 months, unless not desired/contraindicated)

Mental-health professional role

Conduct a biopsychosocial assessment incl. gender history; assess capacity; identify & treat co-occurring mental-health concerns that would interfere with care
Co-occurring mental illness is not an absolute contraindication — it should be reasonably well-controlled, not "cured," before intervention
Hormone therapy improves quality of life, depression, and anxiety in most TGD people
No psychotherapy requirement as a precondition; "conversion/reparative" efforts are unethical & harmful

Other SOC-8 changes worth knowing

New/expanded chapters: nonbinary, eunuch, adolescent, child, primary care, reproductive & sexual health, institutional environments
Adolescents: emphasize a comprehensive multidisciplinary assessment; original numeric age minimums were later removed in a correction — defer to current local clinical guidance
Watch drug interactions: estradiol/anti-androgens and testosterone with psychotropics; monitor mood changes during initiation/titration

Source: Coleman et al., WPATH Standards of Care Version 8, Int J Transgend Health 2022;23(S1):S1–S259.

Cultural Psychiatry & Underrepresented Populations Special Population

Assess culture systematically

Cultural Formulation Interview (CFI) (DSM-5-TR): the patient's definition of the problem, its causes, supports/stressors, role of cultural identity, coping/help-seeking, and treatment expectations
Cultural concepts of distress — idioms ("nervios," "ataque de nervios"), explanatory models, and syndromes shape presentation; don't mistake culturally normative beliefs for psychosis
Use professional interpreters (not family/children); ask about traditional/complementary remedies & their interactions
Practice cultural humility — curiosity and shared decision-making over assumptions

Disparities & bias to counter

Diagnostic bias: Black patients are over-diagnosed with schizophrenia (and under-diagnosed with mood disorders); depression is under-detected/under-treated in many minority groups
Access & treatment gaps: minorities are less likely to be offered buprenorphine, psychotherapy, or newer agents; more likely coercive pathways
Ethnic pharmacology: CYP2D6/2C19 phenotype frequencies & HLA-B*1502 vary by ancestry → dosing/SJS risk (see Pharmacogenomics)
Structural factors (poverty, racism, immigration stress, housing) are social determinants of mental health
Address stigma, language, mistrust, and historical harms to build alliance

DSM-5-TR Cultural Formulation; APA & structural-competency references.

Managing Microaggressions Special Population

Scope: Responding to bias in clinical training and healthcare settings. Broader cultural assessment framework → Cultural Psychiatry.

Microaggressions are everyday verbal/nonverbal/environmental slights — intentional or not — that convey hostile or negative messages based on marginalized-group membership. They are common in training (intimidation/harassment/discrimination ~60%) and are linked to burnout, stereotype threat, imposter syndrome, and traumatic-stress symptoms.

Three types

Microassault: deliberate, conscious slur or act
Microinsult: subtle, insensitive, demeaning comment ("you speak good English")
Microinvalidation: minimizing/discrediting another's experience or feelings

Responding in the moment

Make the invisible visible — challenge the stereotype, broaden the trait, ask for clarification
Disarm — express disagreement, state values & set limits, cite policy
Educate — separate intent from impact, promote empathy
Seek support — alert leadership, report to DEI, debrief with a trusted colleague

Prebrief & debrief: before rounds, acknowledge microaggressions may occur and ask potentially-targeted team members how they'd like incidents handled; afterward, check in 1:1 (don't assume everyone wants to debrief every time). If you are the source — the "ASSIST" model: Acknowledge your bias, Seek feedback, Say you're sorry, focus on Impact not intent, and Say "thank you." Source: ACLP "How-To Guide: Microaggressions" (Chang; Patel & Ruark, 2024).

Forensic Psychiatry Special Population

Competency vs criminal responsibility

Competency to stand trial (Dusky): present ability to understand the proceedings + assist one's attorney — a current-state question
Criminal responsibility / insanity (e.g., M'Naghten): mental state at the time of the offense — didn't know the nature/wrongfulness of the act
Competency to be executed, testamentary capacity, guardianship are separate determinations

Civil & risk

Civil commitment — mental illness + dangerousness/grave disability (see Involuntary Admission)
Violence risk assessment (structured tools, e.g., HCR-20); past violence is the strongest predictor
Malingering assessment (external incentive; see Somatic Disorders)
Role boundaries: the forensic evaluator is not the treating physician (different duty)

Landmark cases & standards

Case / standard	Holding
Dusky v. United States	Competency to stand trial = rational & factual understanding of proceedings + ability to assist counsel
M'Naghten	Insanity = at the time of the act, did not know the nature/quality of the act or that it was wrong (cognitive test)
ALI / Model Penal Code	Lacked substantial capacity to appreciate wrongfulness or conform conduct to law (adds volitional prong)
Tarasoff	Duty to protect an identifiable potential victim (warn, notify, hospitalize)
Wyatt v. Stickney	Right to treatment for the involuntarily committed
O'Connor v. Donaldson	Can't confine a non-dangerous person who can survive in freedom
Rogers / Rennie	Right to refuse treatment (with due process) for committed patients
Estelle v. Gamble	Right to medical/mental-health care for prisoners

Other forensic evaluations: testamentary capacity (know you're making a will, the extent of your estate, the "natural objects of your bounty"), guardianship/conservatorship, disability, fitness-for-duty, child custody, and competency to be executed (Ford v. Wainwright). Malingering vs factitious = external incentive vs the sick role (see Somatic). Standard of proof: civil commitment usually "clear and convincing". Forensic psychiatry references (AAPL).

Forensic Psychiatry — Ohio Statutes Jurisdiction-Specific

Ohio-specific standards under the Ohio Revised Code (ORC). Verify against current statute — this is a study aid, not legal advice.

Competency to stand trial — ORC 2945.37 / .371 / .38

Standard (2945.37): incompetent if, because of a present mental condition, the defendant is incapable of understanding the nature and objective of the proceedings against them or of assisting in their defense (Ohio's codification of Dusky)
Presumed competent; burden is a preponderance of the evidence at the hearing
Evaluations (2945.371): done through certified forensic centers/community resources; municipal courts may not order the eval at a DMH-operated hospital
Restoration (2945.38): if incompetent but restorable, treatment in the least restrictive setting. Max restoration time is capped by offense level — e.g., up to 1 year (aggravated murder/murder/F1–F2), 6 months (F3–F5), shorter for misdemeanors
If not restorable within the limit → charges dismissed; for serious offenses the court may retain jurisdiction under 2945.39 and order commitment if it finds by clear and convincing evidence the person committed the act and is a person with mental illness/IDD subject to court order

Insanity (NGRI) — ORC 2901.01(A)(14) / 2945.391

Cognitive test only: NGRI if, at the time of the offense, because of a severe mental disease or defect, the person did not know the wrongfulness of the act
No volitional prong: ORC 2945.391 states that an inability to refrain from the act ("irresistible impulse") does not constitute a defense — Ohio rejected the ALI volitional arm
Burden on the defense by a preponderance of the evidence (affirmative defense)
Post-acquittal: committed under 2945.40; the commitment term cannot exceed the maximum sentence for the offense; periodic review, conditional release, and least-restrictive-alternative apply

Civil commitment — ORC Chapter 5122

Probate court; clear and convincing evidence; "person with mental illness subject to court order"
Five grounds (5122.01(B)) — (1) risk of harm to self; (2) risk of harm to others; (3) can't provide for basic needs (grave disability); (4) would benefit from treatment & behavior creates a grave and imminent risk to substantial rights of self/others; (5) outpatient-only AOT standard
Ground 5 (AOT) cannot lead to hospitalization — requires unlikely to survive safely without supervision, treatment-noncompliance history (≥2 hospitalizations/forensic stays in 36 mo, or serious violence/threats in 48 mo), unlikely to participate voluntarily, and needs treatment to prevent deterioration
Emergency "pink slip" (5122.10): a psychiatrist, physician, clinical psychologist, psych nurse, health/parole officer, or police may take into custody; exam within 24 h; hold up to 3 court days pending an affidavit
Hearing within 5 court days; initial order up to 90 days, then full hearing, then every 2 years; least restrictive alternative required

Duty to protect & firearms

Duty to protect — ORC 2305.51 (codifying Estates of Morgan v. Fairfield): liability attaches only when the patient (or a knowledgeable person) communicates an explicit threat of imminent, serious physical harm to a clearly identifiable victim, the clinician believes the patient has the intent and ability to act, and fails to take timely action
Discharge the duty by, e.g., a treatment plan/hospitalization reasonably calculated to prevent the act, notifying law enforcement, and/or warning the potential victim
Firearms: a person committed or found to be a person with mental illness subject to court order is under disability — ORC 2923.13 (F3 to possess) and federally barred under 18 USC 922(g)(4); probate court reports to BCI/NICS
Right to refuse medication, ECT, sterilization, psychosurgery is preserved (5122.271) — overriding routine meds needs a separate capacity/court proceeding

High-yield contrasts: Ohio insanity = cognitive-only (knew wrongfulness?), no irresistible-impulse defense. Competency = present ability (2945.37); insanity = at the time of the offense (2901.01(A)(14)). Civil commitment runs through probate court at clear-and-convincing; the 5th 5122.01(B) ground is outpatient-only. ⚠️ Statutes change — confirm current ORC text and case law before relying on this. Sources: Ohio Revised Code Ch. 2945, 2901, 5122, 2305.51, 2923.13.

USMLE Step 3 Review

Exam strategy → medicine/neurology crossover → rapid review & ethics

Exam Strategy

Medicine & Psychiatry Crossover

Neurology

Rapid Review & Ethics

USMLE Step 3 — Exam & CCS Strategy Step 3

Step 3 = two days. Day 1 is MCQs (Foundations); Day 2 adds the CCS (computer-based case simulations) — a half-day of managing simulated patients over advancing clock time. Much of the content is review of Step 1/2.

CCS approach

Order focused history/exam, then treat and monitor — the clock advances; reassess and adjust
Move the patient to the right location (ED → ward/ICU → home) as status changes
Don't forget supportive orders: IV access, O₂, telemetry, VTE prophylaxis, I/Os
Counseling & prevention at the end of every case: smoking cessation, alcohol, diet, exercise, adherence
Practice with the free NBME CCS sample + a case bank; aim 70–80% on "high-yield" cases

Vaccinate everyone eligible (last 2 min of the visit)

Influenza yearly; Tdap q10 yr
Zoster (shingles) if >50
HPV through age 26 (catch-up to 45 shared decision)
Meningococcal for college-age/dorms
Pneumococcal if chronically ill, sickle cell, asplenic, or ≥65

Biostatistics Step 3

Test characteristics

Sensitivity = TP/(TP+FN) = 1 − FN rate (rule OUT: SnNOut)
Specificity = TN/(TN+FP) = 1 − FP rate (rule IN: SpPin)
PPV = TP/all positives — ↑ with prevalence
NPV = TN/all negatives — ↓ with prevalence
LR+ = sensitivity/(1 − specificity); LR− = (1 − sensitivity)/specificity

Risk & effect

NNT = 1/absolute risk reduction; NNH = 1/absolute risk increase
Relative risk reduction = 1 − RR
Odds ratio = odds of exposure in cases ÷ odds in controls (case-control)
RR used in cohort/RCT; OR used in case-control

Screening & Prevention Step 3

Target	Recommendation
Colorectal	Colonoscopy q10 yr ages 45–75 (or sigmoidoscopy q5, or FIT/FOBT q1 → colonoscopy if +). UC: start 8 yr after dx. FAP/Lynch: q1 yr. FHx: colonoscopy at 40 or 10 yr before relative's dx.
Cervical (Pap)	21–29: q3 yr cytology. 30–65: q5 yr with HPV co-test. No Pap before 21 even if sexually active; chlamydia screen if <25. Stop after benign hysterectomy.
Breast (mammogram)	q2 yr ages 40/50–74 (per guideline)
Lung (low-dose CT)	Annual ages 50–80 if ≥20 pack-yr and currently smoke or quit <15 yr ago
AAA (ultrasound)	One-time, men 65–75 who ever smoked
Lipids	Men >35, women >45 (earlier if CAD risk)
Diabetes complications	Retinopathy: screen 5 yr post-dx (T1DM) / at dx (T2DM). Nephropathy: 5 yr post-dx (T1DM) / at dx (T2DM). Statin if DM + >40 yo.

Osteoporosis: T-score ≤ −2.5 → bisphosphonate (alendronate). Osteopenia (−1 to −2.5) → calculate 10-yr fracture risk (FRAX), then decide. Ca²⁺ ≥1200 mg/day.

Cardiology Step 3

Murmurs

Systolic: Aortic stenosis (crescendo-decrescendo, RUSB → "SAD": syncope/angina/dyspnea); mitral regurgitation (holosystolic blowing, apex); MVP (mid-systolic click → late murmur); tricuspid regurg (holosystolic, LLSB; ↑ inspiration); VSD (harsh holosystolic — louder = smaller defect).

Diastolic ("AR-MS"): Aortic regurg (early decrescendo, LSB, wide pulse pressure); Mitral stenosis (opening snap → rumble, apex; rheumatic → AFib/hemoptysis)

ECG leads → vessel

Inferior II, III, aVF → RCA
Lateral I, aVL → LCX
Anteroseptal V1–V2 → LAD
Anteroapical V3–V4 → distal LAD
Anterolateral V5–V6 → LAD/LCX
Posterior ST depression V1–V3 + tall R

ACS: ABCDE; ECG, troponin, telemetry, IV, O₂ if <90%. STEMI → immediate PCI. NSTEMI (ST-depression/T-inversion) → serial troponin/ECG; PCI if unstable, refractory angina, posterior infarct, or left-main. Meds: ASA, high-intensity statin, β-blocker (not if HF/shock/hypotension), ACE-I, ± aldosterone antagonist. Discharge: aspirin, statin, clopidogrel, metoprolol, nitroglycerin, lisinopril + smoking cessation.

Long QT, Torsades & Conditions Affecting QTc Step 3

The medical review behind the psychiatric QTc section — what prolongs the QT and how torsades is managed.

Conditions / risk factors that prolong QTc

Electrolytes: hypokalemia, hypomagnesemia, hypocalcemia (the classic triad)
Bradycardia & pauses; sleep
Cardiac: prior arrhythmia, LV dysfunction / CHF, recent MI, mitral valve prolapse, myocarditis
Congenital long QT syndrome (mutations in ≥10 genes; LQT1–3 most common)
Demographics: female sex, older age; hepatic impairment (↓ drug clearance)
Endocrine/metabolic: hypothyroidism, hypoglycemia, anorexia/starvation; SAH/stroke (neurogenic)
Drugs & drug–drug interactions (CYP inhibition stacking) — see QTc section

Congenital long QT syndrome — high-yield

LQT1 (Kᵥ7.1/I_Ks): events with exercise/swimming; β-blockers help
LQT2 (hERG/I_Kr): events with emotion/auditory startle (alarm clock)
LQT3 (Na channel SCN5A): events during sleep/rest
Romano-Ward (AD, pure cardiac); Jervell-Lange-Nielsen (AR, + congenital deafness)

Torsades de pointes — management: polymorphic VT on a prolonged QT (syncope/sudden death). Unstable → defibrillate. Stable: IV magnesium sulfate (first-line, even if Mg normal), correct K⁺/Ca²⁺, stop all QT-prolonging drugs. For pause/bradycardia-dependent TdP: increase the rate (overdrive pacing or isoproterenol) to shorten the QT. Definitive: treat the cause; β-blockers ± ICD for congenital LQTS. Standard cardiology references.

CCS Emergency Management Step 3

Scenario	Key management
COPD exacerbation	Duonebs (albuterol+ipratropium)+O₂; prednisone (IV if severe); azithromycin ×7 d; BiPAP if pH<7.3 or pCO₂>45. Discharge: home-O₂ eval, vaccines, smoking cessation.
CHF exacerbation	Stable: furosemide, nitrates, SGLT2i, low-Na. Unstable: NIPPV/intubation, dobutamine inotropy, urgent PCI/CCU.
Hypertensive emergency (>180/120 + end-organ damage)	STAT head CT (if stroke, don't lower fast); IV nitroprusside/labetalol/nicardipine; lower ≤25% in first hours; A-line, ICU.
DKA / HHS	IVF (NS), K⁺ repletion before insulin if K<3.3, IV insulin, switch to D5 when glucose <200 (DKA)/<300 (HHS); monitor q2h.
Sepsis (SIRS ≥2)	Temp <36/>38, HR>90, RR>20, WBC abnormal → pan-culture (blood/urine), CXR, fluids, early antibiotics.
Preeclampsia w/ severe features	IV magnesium sulfate (seizure ppx), labetalol or hydralazine (not nicardipine), deliver if ≥34 wk; betamethasone if 24–34 wk.
Overdose (ICU)	Naloxone, activated charcoal, O₂, fluids; suicide precautions; serum tox/TCA level; TCA + wide QRS → NaHCO₃; consider CO.
Cholecystitis	RUQ U/S (Murphy sign) → HIDA if unclear; antibiotics (amp-sulbactam, pip-tazo, or ceftriaxone+metronidazole).

High-Yield Rapid Facts Step 3

Pearls

Heterophile +/mono = EBV; no contact sports ≥4 wk (splenic rupture)
TCA toxicity + wide QRS → NaHCO₃; electrical alternans → tamponade
Lewy body dementia: avoid strong D2-blocker antipsychotics → low-dose quetiapine
Factor V Leiden = activated protein C resistance
MTX macrocytic anemia → leucovorin (folinic acid), not folate
Ectopic: stable → methotrexate, unstable → surgery
Raynaud's → CCB (nifedipine/amlodipine); septic joint WBC >50,000
Suspected testicular cancer → ultrasound, never biopsy → radical orchiectomy
Asthma exacerbation → prednisone 40 mg ×5 d (no taper)

Most important risk / prognostic factor

AAA: smoking (risk); diameter (rupture)
Melanoma: depth (Breslow)
Breast cancer: axillary node involvement
HCC prevention: Hep B vaccination
Esophageal adenocarcinoma: Barrett's (not GERD)
Endometrial cancer: unopposed estrogen (tamoxifen, PCOS)
Cervical cancer: HPV 16/18; prognosis = stage
OSA: obesity (risk) → associated with heart failure
C. diff: antibiotics + hospitalization

Oncogenic infections: HPV → cervical/anal/head&neck; EBV → Hodgkin (Reed-Sternberg), Burkitt (t8;14, "starry sky"), post-transplant lymphoma; H. pylori → MALT; Hep B/C → HCC; HHV-8 → Kaposi.

Alpha-2 Agonists & Sedation Tapering Clinical Reference

From your uploaded tables — relevant to ADHD, autonomic/withdrawal management, and ICU sedation (dexmedetomidine).

Clonidine vs. guanfacine

Feature	Clonidine	Guanfacine
Mechanism	α₂-adrenergic agonist	α₂-adrenergic agonist (more selective)
Half-life	~12 h	~17 h
Dosing	q8–12 h	Once daily
Onset	~30–60 min	~1–4 h
Sedation	More sedating	Less sedating
Hypotension / rebound HTN	Higher risk	Lower risk
Preferred use	Acute withdrawal, short-term	Longer-term, smoother
Taper	↓ dose q1–2 days (avoid rebound HTN)	↓ dose q2–3 days (slower)

Dexmedetomidine wean / transition

Method	Schedule	Monitor
Gradual wean	↓ by 0.1 mcg/kg/hr q6–12 h; stop when ≤0.2 mcg/kg/hr	Hypertension, tachycardia, agitation, withdrawal
Transition to clonidine	Start clonidine 0.1 mg PO q8–12 h; ↓ Dex 0.2 mcg/kg/hr q6–12 h until off; taper clonidine over 3–5 d	Rebound hypertension
Transition to guanfacine	Start guanfacine 0.5–1 mg PO daily; ↓ Dex 0.1–0.2 mcg/kg/hr q12 h until off; taper guanfacine over 5–7 d	Withdrawal; taper slowly

Dexmedetomidine is a centrally-acting α₂ agonist used for ICU sedation (and procedural sedation); abrupt discontinuation can cause rebound hypertension/tachycardia/agitation — hence the structured wean or α₂-agonist bridge.

Endocrine — Adrenal Insufficiency Medicine

High psychiatric relevance: AI mimics depression (fatigue, anorexia, weight loss, low mood) and is the reason chronic steroids must never be stopped abruptly. Presentation: fatigue, nausea/vomiting, anorexia & weight loss, abdominal pain, muscle/joint pain, salt craving, orthostatic hypotension, hyponatremia — and hyperpigmentation (primary only).

Adrenal crisis = emergency. If hemodynamically unstable, do not wait for labs → high-dose parenteral glucocorticoid (hydrocortisone 100 mg IV, then 50 mg q6h) + IV normal saline (± dextrose) + treat the precipitant (infection, missed dose, surgery). Draw a cortisol/ACTH first if it won't delay treatment, or use dexamethasone (doesn't interfere with the cortisol assay).

Diagnostic algorithm — early-morning cortisol + ACTH (corticotropin) + DHEAS

Morning cortisol	ACTH	DHEAS	Interpretation
<5 µg/dL (AI confirmed)	Elevated	Low	Primary adrenal insufficiency (Addison)
<5 µg/dL (AI confirmed)	Low / normal	Low	Secondary AI or glucocorticoid-induced AI
5–10 µg/dL (indeterminate)	Low / normal	Low	Clinical judgment → likely secondary AI
5–10 µg/dL (indeterminate)	Mid–high	Mid–high	Repeat labs or do an ACTH (cosyntropin) stimulation test ↓
>10 µg/dL	Normal	Normal	Very low probability of clinically relevant AI

ACTH stimulation test result: stimulated cortisol ≤5 µg/dL or inadequate rise → confirms AI (secondary); >10 µg/dL / adequate rise → AI effectively excluded.

Primary (Addison)

Adrenal gland fails → ↓cortisol AND ↓aldosterone; ACTH ↑ (loss of feedback).

Hyperpigmentation (↑ACTH/POMC → MSH)
Hyperkalemia, hyponatremia, salt craving (aldosterone loss)
Causes: autoimmune (most common in developed world), TB, adrenal hemorrhage (Waterhouse-Friderichsen), metastases

Secondary

Pituitary ACTH deficiency → ↓cortisol; aldosterone preserved (RAAS intact).

No hyperpigmentation, no hyperkalemia
Hyponatremia possible (SIADH-like, from cortisol loss)
Causes: pituitary tumor/surgery/radiation, Sheehan syndrome, apoplexy

Tertiary / steroid-induced

Chronic exogenous glucocorticoids suppress CRH/ACTH → adrenal atrophy. Most common cause overall.

Low DHEAS, low/normal ACTH
Never stop chronic steroids abruptly → taper
Relevant to psychiatry: long-term steroid patients

Treatment: Glucocorticoid replacement — hydrocortisone (10–12 mg/m²/day divided, mimicking diurnal rhythm) or prednisone. Primary AI also needs a mineralocorticoid: fludrocortisone. DHEA replacement is optional (may help mood/libido in women). Sick-day rules: double or triple the glucocorticoid dose during illness/fever; stress-dose (IV hydrocortisone) for surgery; patients should carry an emergency injectable and a medical-alert card. Source: diagnostic algorithm adapted from the uploaded figure.

Medical Mimics — Step 3 Rapid Review Step 3 · Cross-Ref

Scope: Board-exam triggers only. Full differential, workup, and clinical depth → Chapter 1 — Medical Mimics of Psychiatric Illness.

When a vignette presents psychiatric symptoms, scan for these high-yield organic causes before locking in a primary psychiatric diagnosis.

Endocrine & metabolic (classic Step 3)

Hyperthyroidism → anxiety, mania, insomnia; elderly "apathetic" form → depression
Hypothyroidism → depression, cognitive slowing, "myxedema madness"
Cushing / Addison → depression, psychosis, apathy; Addison → hypotension, hyperpigmentation
Hyperparathyroidism / hypercalcemia → depression, psychosis, confusion
Pheochromocytoma → panic-like spells + episodic HTN
Hypoglycemia → anxiety, bizarre behavior — always check glucose

Nutritional, infectious & neurologic

Thiamine (B1) → Wernicke → Korsakoff; give thiamine before glucose
B12/folate → depression, psychosis, dementia, neuropathy
Neurosyphilis, HIV, HSV encephalitis (temporal lobe, fever, seizures)
Anti-NMDA encephalitis → young woman + psychosis → seizures/dyskinesia; check for ovarian teratoma
Wilson disease (young + psych + movement disorder + liver); porphyria (5 P's); hepatic/uremic encephalopathy

Medication & substance triggers

Steroids, interferon, levodopa/dopamine agonists, anticholinergics, stimulants — review the med list
Intoxication/withdrawal from alcohol, stimulants, hallucinogens, PCP, sedatives

Step 3 workup when organic is on the differential: CBC, CMP (Na/Ca/glucose/LFTs/renal), TSH, B12/folate, UDS, RPR & HIV; ± ammonia, ceruloplasmin; MRI/CT for focal signs, new psychosis >40, or delirium; EEG/LP when encephalitis or seizures suspected. For full tables and first-episode psychosis protocol → Chapter 1.

Neurology I — Stroke, Seizures, Headache & Trauma Step 3 · Neurology

High-yield neurology for the psychiatry-adjacent clinician. Verify acute protocols against current AHA/ASA & institutional guidelines — windows and agents evolve.

Stroke — types & acute management

Ischemic (~85%): non-contrast CT first to exclude hemorrhage. IV thrombolysis (alteplase or tenecteplase) within 4.5 h of last-known-well (tenecteplase 0.25 mg/kg, max 25 mg, if going to thrombectomy). Mechanical thrombectomy up to 24 h for large-vessel occlusion with favorable perfusion imaging (DAWN/DEFUSE-3)
Hemorrhagic (~15%): intracerebral (control BP, reverse anticoagulation) vs subarachnoid ("worst headache of life", thunderclap → CT, then LP for xanthochromia; aneurysmal → coil/clip, nimodipine for vasospasm)
tPA contraindications: recent surgery/bleed, BP >185/110, recent stroke/head trauma, anticoagulation, glucose extremes
Secondary prevention: antiplatelet, statin, BP & glucose control, anticoagulate if AFib, carotid endarterectomy for symptomatic high-grade stenosis

Stroke syndromes by territory

ACA: contralateral leg > arm weakness, abulia
MCA: contralateral face/arm weakness & sensory loss; aphasia (dominant) or neglect (non-dominant); eyes deviate toward lesion
PCA: contralateral homonymous hemianopia, ± alexia
Lacunar (small-vessel, HTN): pure motor or pure sensory; internal capsule/pons
Brainstem/vertebrobasilar: crossed signs, Wallenberg (lateral medullary), locked-in (basilar)
Amaurosis fugax (transient monocular blindness) = carotid TIA warning

Seizures & epilepsy

Focal (aware vs impaired awareness) vs generalized (tonic-clonic, absence, myoclonic, atonic)
Provoked (alcohol/benzo withdrawal, hypoglycemia, hyponatremia, eclampsia, drugs — bupropion, clozapine, tramadol lower threshold) vs unprovoked (epilepsy)
First unprovoked seizure: EEG + MRI; counsel driving restrictions
Status epilepticus (≥5 min or recurrent without recovery) = emergency: ABCs, glucose, IV benzodiazepine first-line (lorazepam) → levetiracetam, fosphenytoin, or valproate (equivalent, ESETT) → refractory: anesthesia (propofol/midazolam), intubate, EEG
PNES (psychogenic non-epileptic spells): no epileptiform EEG; video-EEG is gold standard; managed psychiatrically (often trauma/conversion)

Headache — recognize the dangerous ones

Migraine: unilateral, throbbing, photophobia/phonophobia, nausea, ± aura; triptans/NSAIDs acute, prophylaxis (propranolol, topiramate, amitriptyline, CGRP mAbs)
Tension: bilateral, band-like, no nausea
Cluster: severe unilateral periorbital, autonomic (tearing, rhinorrhea), restless; high-flow O₂ + triptan
Red flags (image/workup): thunderclap (SAH), fever + stiff neck (meningitis), papilledema/↑ICP, new headache >50 with jaw claudication (giant cell arteritis → ESR, steroids, biopsy), focal deficit, worst-with-Valsalva, immunosuppressed
Idiopathic intracranial hypertension: obese young women, papilledema, ↑opening pressure; acetazolamide, weight loss

Head trauma & raised ICP

Epidural hematoma: trauma → lucid interval → deterioration; biconvex/lens CT (middle meningeal artery)
Subdural hematoma: crescent-shaped, bridging veins; elderly/alcoholics/anticoagulated; can be chronic (fluctuating cognition — a dementia mimic)
Concussion/TBI: rest, graded return; watch for post-concussive depression, anxiety, cognitive symptoms
↑ICP: headache, vomiting, papilledema, Cushing triad (HTN, bradycardia, irregular respirations); herniation → blown pupil (CN III). Treat: head up, hyperventilation (temporizing), mannitol/hypertonic saline, neurosurgery
Normal-pressure hydrocephalus: "wet, wobbly, wacky" (incontinence, gait, dementia) — potentially reversible with shunt

Neurology II — Movement, Demyelinating, Neuromuscular, Cord & Infection Step 3 · Neurology

Movement disorders

Parkinson disease: resting tremor, rigidity, bradykinesia, postural instability (TRAP); Lewy bodies; treat levodopa-carbidopa, dopamine agonists, MAO-B inhibitors. Watch psychosis (treat with pimavanserin/quetiapine/clozapine; avoid typical antipsychotics)
Essential tremor: action/postural tremor, improves with alcohol, family history; propranolol or primidone
Huntington disease: AD, CAG repeat; chorea + psychiatric (depression, irritability) + dementia; caudate atrophy
Wilson, tardive dyskinesia, dystonia, tics/Tourette, restless legs (iron, dopamine agonists)
Drug-induced parkinsonism from antipsychotics/metoclopramide — key psych overlap

Demyelinating & neuromuscular

Multiple sclerosis: young women, lesions "separated in space & time"; optic neuritis, INO, sensory/motor, fatigue, depression & cognitive change; MRI + oligoclonal bands; disease-modifying therapy
Guillain-Barré: ascending paralysis, areflexia, post-infectious (Campylobacter); albuminocytologic dissociation; IVIG/plasmapheresis, watch respiratory failure
Myasthenia gravis: fatigable weakness, ptosis, diplopia; anti-AChR; thymoma; pyridostigmine. (Distinguish from Lambert-Eaton — improves with use, small-cell lung cancer)
ALS: upper + lower motor neuron, no sensory loss; riluzole
Peripheral neuropathy: diabetes, B12, alcohol, chemo; stocking-glove

Spinal cord & CNS infection

Cord compression (mets, abscess, trauma): back pain, weakness, sensory level, bowel/bladder — emergent MRI + steroids
B12 subacute combined degeneration: dorsal columns + corticospinal (also a psych/dementia cause)
Cauda equina: saddle anesthesia, urinary retention — surgical emergency
Meningitis: fever, stiff neck, photophobia, ↓mental status; LP (bacterial = ↑PMNs, ↓glucose); empiric ceftriaxone + vancomycin (+ ampicillin if elderly/immunocompromised) + dexamethasone; don't delay antibiotics for CT/LP
Encephalitis (HSV — temporal lobe, acyclovir) vs brain abscess (ring-enhancing)

Neuro-oncology, vertigo & consciousness

Brain tumors: adults — mets (lung, breast, melanoma) > glioblastoma, meningioma; kids — posterior fossa (medulloblastoma, pilocytic astrocytoma); morning headache, seizures, focal/personality change
Vertigo: peripheral (BPPV — Dix-Hallpike/Epley; vestibular neuritis; Ménière) vs central (brainstem/cerebellar stroke — other neuro signs, vertical/direction-changing nystagmus)
Coma: structural vs metabolic; assess GCS, brainstem reflexes; brain death = irreversible loss of all brain/brainstem function (coma, absent brainstem reflexes, apnea test), confirm no confounders (hypothermia, sedatives, metabolic)
Delirium vs dementia vs depression — see Neuropsychiatry & Delirium sections

Localization quick cues: cortical signs (aphasia, neglect, seizures) = cortex; crossed face/body = brainstem; sensory level + bladder = cord; areflexia + ascending = peripheral (GBS); fatigability = NMJ. Always separate UMN (spasticity, hyperreflexia, ↑tone, Babinski) from LMN (atrophy, fasciculations, areflexia, ↓tone). ⚠️ Educational review — confirm management against current neurology guidelines. Standard references (First Aid / Step 3-level neurology; AHA/ASA stroke guidance).

Ethics & Legal Essentials Step 3

Core principles & confidentiality

Four principles: autonomy, beneficence, non-maleficence, justice
Informed consent: capacity + disclosure (risks/benefits/alternatives) + voluntariness; exceptions: emergency, waiver, therapeutic privilege (rare)
Minors: parental consent + assent; exceptions — emancipated minors, and care for STIs, contraception, substance use, mental health (varies by state)
Confidentiality with limits — see breaches below; HIPAA governs disclosure

Duties & mandated breaches

Tarasoff / duty to protect — identifiable potential victim → warn/protect (notify, hospitalize, notify police per jurisdiction)
Mandatory reporting: suspected child/elder/dependent-adult abuse; certain communicable diseases; impaired drivers (state-dependent)
Civil commitment — danger to self/others or grave disability (see Involuntary Admission)
EMTALA — must screen/stabilize emergencies regardless of ability to pay
Capacity vs competence (clinical vs court) — see Capacity to Consent

Standard medical ethics/forensic references.

Mental Status Exam Clinical Skill

Describing the tricky domains — terms defined

Speech (describe the form, not the content)

Affect — describe 6 features (mood = what they say; affect = what you see)

Thought process — glossary

Insight & Judgment — how to grade and phrase it

Medical Mimics of Psychiatric Illness Differential

Red flags for a medical/organic etiology

Rating Scales & Screening Instruments Assessment

Depression

Anxiety

Bipolar / Mania

Trauma / PTSD

OCD

Psychosis

ADHD

Substance Use

Eating Disorders

Dissociation

Personality / Borderline

Cognitive Screening

Delirium

Drug-Induced Movement

Sleep

Suicide · Catatonia · Global

Diagnostic Mnemonics Reference

Mood / affective

Anxiety / trauma

Medication-effect syndromes

Addiction

Delirium

Personality disorders

Clinical Calculators Reference

Risk Assessment — Suicide & Violence Clinical Skill

The framework: chronic vs acute risk

Lowering risk through protective factors (the disposition work)

Acute risk levels & disposition

Most indicative RISK factors

Most indicative PROTECTIVE factors

Key epidemiology

Psychosis-Risk Screening (Mini-SIPS / APS) Clinical Skill

Three symptom classes queried

APS diagnosis — all must be true

Capacity to Consent Clinical Skill

The four functional components (Appelbaum & Grisso)

Capacity vs competence & the consult in practice

Involuntary Admission ("Pink Slip") Clinical Skill

Two things must both be true

Objective criteria — need ≥1

Who can initiate & what to document

Writing a Case Report — CARE Checklist Scholarly

Using Algorithms — Principles Evidence-Based Practice

Why evidence-informed practice

Qualities of a good algorithm

Schizophrenia Algorithm

Bipolar Mania Algorithm

Bipolar Depression Algorithm

First-line agents — starting & titration schedules

Unipolar (Non-Psychotic) Depression Algorithm

Comorbidity-targeted options

Psychotic Depression Algorithm

Panic Disorder Algorithm

Generalized Anxiety Disorder Algorithm

Social Anxiety Disorder Algorithm

Obsessive-Compulsive Disorder Algorithm

Y-BOCS — measuring severity & treatment response

Posttraumatic Stress Disorder Algorithm

Antidepressants — Quick Reference

Antipsychotics — Quick Reference

Bipolar / Mood Stabilizer Quick Reference

Bipolar Maintenance Treatment Medication Reference

Anxiolytics & Hypnotics — Quick Reference

Benzodiazepines

Other anti-anxiety agents

Hypnotics

Stimulants & Over-the-Counter

Psychostimulants

Over-the-counter

Anti-obsessional (often higher doses than for depression)

Newer & Targeted Agents Medication Reference

Receptor binding affinity (K_i, nM) — lower = stronger binding