Psychopharmacology
Psychopharmacology
What Do You Need to Know?
- SSRIs are first-line antidepressants; key side effects include sexual dysfunction, GI upset, serotonin syndrome, and QTc prolongation (citalopram); paroxetine is the most anticholinergic and worst in pregnancy
- Serotonin syndrome vs NMS — serotonin syndrome: clonus + hyperreflexia (onset hours, treat with cyproheptadine); NMS: lead-pipe rigidity + elevated CK (onset days–weeks, treat with dantrolene + bromocriptine)
- Antipsychotic-induced movement disorders follow a time course: acute dystonia (hours) → akathisia (days) → parkinsonism (weeks) → tardive dyskinesia (months–years)
- PD psychosis: pimavanserin is FDA-approved (5-HT2A inverse agonist, no D2); clozapine has the strongest efficacy data but requires ANC monitoring for agranulocytosis; quetiapine is commonly used (low D2 affinity, practical ease) — mixed efficacy data, calling it "safest" is too strong. For DLB, all antipsychotics need caution (neuroleptic sensitivity + dementia mortality)
- Lithium has a narrow therapeutic index — causes tremor, hypothyroidism, nephrogenic DI, and Ebstein anomaly (teratogen); requires level/TSH/renal monitoring
- Benzodiazepines are GABA-A positive allosteric modulators (increase Cl− opening frequency); reversed by flumazenil; withdrawal seizures are a major concern
- Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) for mild–moderate AD; memantine (NMDA antagonist) for moderate–severe AD; anti-amyloid mAbs require ARIA monitoring
🚩 Don’t Miss — Test-Day Priorities
- Citalopram QTc: max 40 mg/day overall, ≤20 mg/day if >60 yr or hepatic impairment — classic board trap dose
- Serotonin syndrome triggers: SSRI/SNRI + MAOI, tramadol, linezolid (reversible MAOI), methylene blue, MDMA, triptans, St John’s wort → clonus + hyperreflexia (lower-limb predominant) + autonomic instability; treat with cyproheptadine + supportive care
- Bupropion lowers seizure threshold → contraindicated in eating disorders, alcohol/BZD withdrawal, and seizure history; favored in elderly for low sexual SE and apathy
- Lithium toxicity: cerebellar signs + dysarthria + tremor + AMS ± seizures; SILENT syndrome (irreversible neurotoxicity) after severe/prolonged toxicity; avoid dehydration, NSAIDs, thiazides, ACE-i; treat severe toxicity with hemodialysis
- Antipsychotics in PD/DLB: AVOID haloperidol and high-D2 typicals. For PD psychosis: pimavanserin (5HT2A inverse agonist, no D2) is FDA-approved; clozapine has strongest efficacy but needs ANC monitoring; quetiapine commonly used (low D2 affinity, practical) — mixed efficacy. For DLB, all antipsychotics need caution (neuroleptic sensitivity + dementia mortality)
- Clozapine REMS: agranulocytosis (weekly ANC × 6 mo) + myocarditis + seizures (dose-dependent) + sialorrhea + metabolic syndrome — most effective for refractory schizophrenia
- BLACK BOX: all antipsychotics ↑ mortality in elderly with dementia; brexpiprazole (2023) is FDA-approved for agitation in Alzheimer dementia
- Lamotrigine + valproate: VPA inhibits LTG glucuronidation → ↑ SJS/TEN risk; titrate LTG even slower (halve the dose) when combined
- Zolpidem complex sleep behavior (sleep-driving, sleep-eating) + falls/delirium in elderly; benzodiazepines & Z-drugs on Beers list — avoid in NCD; flumazenil reverses BZD but may precipitate seizures
- Modafinil/armodafinil are CYP3A4 inducers → reduce efficacy of OCPs (counsel backup contraception); used for narcolepsy, OSA with residual sleepiness, shift-work disorder
🔍 Buzzwords & Pathognomonic FindingsMechanism · Adverse effects · Interactions / use
Mechanism
- Bupropion → NDRI (NE + DA reuptake inhibition)
- Mirtazapine → α2 antagonist + 5HT2/5HT3 antagonist (noradrenergic + specific serotonergic, NaSSA)
- Trazodone → 5HT2A antagonist + weak SERT inhibitor (SARI)
- Pimavanserin → selective 5HT2A inverse agonist with no D2 activity
- Aripiprazole / brexpiprazole → D2 partial agonist + 5HT1A partial agonist
- Buspirone → 5HT1A partial agonist (non-sedating anxiolytic)
- Varenicline → α4β2 nicotinic partial agonist
- Esketamine → NMDA antagonist (intranasal, S-enantiomer of ketamine)
- Modafinil → DA reuptake + histaminergic/orexin activation
- Atomoxetine → selective NE reuptake inhibitor (non-stimulant ADHD)
Adverse effects
- QTc prolongation → citalopram (dose-limited), ziprasidone, IV haloperidol, TCAs
- Hyponatremia / SIADH → SSRIs (esp. elderly), SNRIs, carbamazepine
- Priapism → trazodone
- Agranulocytosis → clozapine (weekly CBC monitoring)
- Tyramine crisis (aged cheese, cured meats, red wine) → MAOIs (phenelzine, tranylcypromine)
- Stevens-Johnson syndrome → lamotrigine (slow titration; worse with VPA)
- SILENT (syndrome of irreversible lithium-effectuated neurotoxicity) → lithium
- Nephrogenic DI + hypothyroidism + Ebstein anomaly → lithium
- Lowered seizure threshold → bupropion, clozapine, TCAs
- Metabolic syndrome / weight gain (worst) → olanzapine & clozapine
- Complex sleep behavior (sleep-driving) → zolpidem (Z-drugs)
- Smoking cessation: FDA REMOVED the neuropsychiatric boxed warning for varenicline and bupropion in December 2016 (after EAGLES trial) — monitoring for neuropsychiatric symptoms remains appropriate. Bupropion as an antidepressant still carries the class suicidality boxed warning in young patients (<24).
Interactions / use
- Linezolid + SSRI/SNRI → serotonin syndrome (linezolid is a reversible MAOI)
- Cyproheptadine → antidote for serotonin syndrome (5HT2A antagonist)
- Hemodialysis → severe lithium toxicity (level ≥4.0 or symptomatic ≥2.5)
- Modafinil / CBZ CYP3A4 induction → OCP failure (counsel backup contraception)
- PD psychosis: pimavanserin FDA-approved; clozapine strongest efficacy (needs ANC monitoring); quetiapine commonly used but mixed efficacy — not "safest"; DLB → all antipsychotics need caution (neuroleptic sensitivity + dementia mortality); AVOID haloperidol
- Brexpiprazole → FDA-approved (2023) for agitation in Alzheimer dementia
- Duloxetine → diabetic peripheral neuropathy + fibromyalgia + depression
- Sertraline → preferred SSRI in pregnancy and breastfeeding (paroxetine worst — cardiac teratogen)
- Fluoxetine → 5-week washout before starting MAOI (long half-life)
- Methylphenidate / amphetamines → ADHD + narcolepsy + apathy in dementia (off-label)
- Naltrexone → μ-opioid antagonist for alcohol craving (avoid in active opioid use — precipitates withdrawal)
- Flumazenil → reverses BZD overdose (caution: may precipitate seizures in chronic users)
Antidepressants
Antidepressant Classes
| Class | Examples | Mechanism | Key Side Effects | Board-Yield Points |
|---|---|---|---|---|
| SSRIs | Fluoxetine, sertraline, paroxetine, citalopram, escitalopram | Selective serotonin reuptake inhibition | Sexual dysfunction; GI (nausea, diarrhea); serotonin syndrome (with MAOIs, triptans, tramadol, linezolid) | Citalopram: QTc prolongation (max 40 mg/day, 20 mg if >60 yr). Paroxetine: most anticholinergic SSRI, shortest half-life, worst in pregnancy. Fluoxetine: longest half-life, strong CYP2D6 inhibitor |
| SNRIs | Venlafaxine, duloxetine | 5-HT + NE reuptake inhibition | Hypertension (venlafaxine); discontinuation syndrome | Duloxetine: FDA-approved for diabetic neuropathic pain and fibromyalgia. Venlafaxine: SSRI-like at low doses, NE effect at higher doses |
| TCAs | Amitriptyline, nortriptyline, desipramine, imipramine | 5-HT + NE reuptake + anticholinergic, antihistaminic, α1-blocking | Anticholinergic (dry mouth, urinary retention). Cardiac: Na+ channel blockade → QRS widening. Seizures in overdose | Nortriptyline: less sedating than amitriptyline; used for neuropathic pain. TCA overdose: treat with sodium bicarbonate. Amitriptyline: migraine prophylaxis |
| MAOIs | Phenelzine, tranylcypromine | Irreversible MAO-A/B inhibition → ↑ 5-HT, NE, DA | Tyramine crisis (aged cheese, red wine, cured meats); serotonin syndrome with SSRIs/meperidine | 2-week washout when switching to/from SSRIs (5 weeks for fluoxetine). Selegiline: MAO-B selective at low doses (used for PD) |
| Bupropion | Bupropion (Wellbutrin, Zyban) | NDRI (norepinephrine/dopamine reuptake inhibitor) | Lowers seizure threshold; insomnia, agitation; less sexual dysfunction | Contraindicated in bulimia/anorexia and seizure history; useful for smoking cessation; less sexual dysfunction than SSRIs |
| Trazodone | Trazodone | 5-HT2A antagonist; SARI | Sedation, orthostasis, priapism (rare but emergent) | Frequently used off-label for insomnia; low risk of dependence |
| Nefazodone | Nefazodone | 5-HT2A antagonist + weak SNRI | Boxed warning hepatotoxicity | Largely abandoned due to hepatotoxicity |
| Mirtazapine | Mirtazapine | Alpha-2 antagonist + H1 antagonist (NaSSA) | Sedation, weight gain, appetite stimulation | Useful in cachexia, anorexia, insomnia; minimal sexual dysfunction |
Board Pearl
TCA overdose is a medical emergency: altered mental status, seizures, and cardiac arrhythmias (widened QRS from Na+ channel blockade). First-line treatment is IV sodium bicarbonate. QRS >100 ms predicts seizures; QRS >160 ms predicts ventricular arrhythmias. Never use class IA/IC antiarrhythmics (further Na+ channel blockade).
Board Pearl
MAOI + tyramine interaction: MAOIs prevent intestinal/hepatic degradation of dietary tyramine → massive catecholamine release → hypertensive crisis (severe headache, hypertension, risk of intracerebral hemorrhage). Patients must avoid aged cheeses, cured meats, red wine, soy sauce, and draft beer. A 2-week washout is required when switching between MAOIs and serotonergic drugs (5 weeks for fluoxetine due to its long half-life and active metabolite norfluoxetine).
Serotonin Syndrome vs Neuroleptic Malignant Syndrome
Comparison Table
| Feature | Serotonin Syndrome | NMS |
|---|---|---|
| Cause | Serotonergic excess (SSRI + MAOI, SSRI + triptan, SSRI + linezolid, SSRI + tramadol; also MDMA, St John's wort, methylene blue, dextromethorphan, fentanyl) | D2 blockade (antipsychotics) or rapid withdrawal of dopaminergic agents |
| Onset | Hours (within 24 hr of drug change) | Days to weeks after initiation or dose increase |
| Neuromuscular | Clonus (hallmark), hyperreflexia, myoclonus, tremor; lower extremities > upper | "Lead-pipe" rigidity (hallmark), bradyreflexia |
| Mental status | Agitation, confusion | Altered consciousness, stupor, catatonia |
| Autonomic | Hyperthermia, tachycardia, diaphoresis, mydriasis, diarrhea | Hyperthermia (≥40°C), autonomic instability (labile BP, tachycardia), diaphoresis |
| Labs | Usually normal CK; mild leukocytosis | Markedly elevated CK (rhabdomyolysis), leukocytosis, metabolic acidosis, renal failure |
| Treatment | Stop offending agent; cyproheptadine (5-HT2A antagonist); benzodiazepines; supportive cooling | Stop offending agent; dantrolene (muscle relaxant) + bromocriptine (DA agonist); supportive cooling |
| Resolution | Usually within 24–72 hours | Resolution over 1–2 weeks (longer if depot antipsychotic) |
Board Pearl
The key differentiator: clonus with hyperreflexia = serotonin syndrome; lead-pipe rigidity with bradyreflexia = NMS. Both cause hyperthermia, but NMS typically produces higher temperatures with markedly elevated CK from rhabdomyolysis.
Antipsychotics
First-Generation (Typical) vs Second-Generation (Atypical)
| Feature | Typical (First-Gen) | Atypical (Second-Gen) |
|---|---|---|
| Mechanism | Primarily D2 blockade | D2 blockade + 5-HT2A antagonism |
| Examples | Haloperidol, chlorpromazine, pimozide | Quetiapine, olanzapine, risperidone, clozapine, aripiprazole |
| EPS risk | High (especially haloperidol) | Lower (risperidone at high doses → EPS) |
| Metabolic | Lower | Higher (worst: olanzapine, clozapine) |
| QTc | Yes (haloperidol IV, chlorpromazine) | Ziprasidone highest risk |
| Prolactin | Elevated | Variable (risperidone highest; aripiprazole lowest) |
High-Yield Individual Antipsychotics
| Drug | Unique Features | Board-Yield Points |
|---|---|---|
| Clozapine | Most effective for refractory schizophrenia | Severe neutropenia/agranulocytosis ~0.4–0.8% cumulative (historical estimates 1–2% before mandatory monitoring) — requires ANC monitoring weekly × 6 mo → every 2 weeks for months 7–12 → every 4 weeks after 12 months. Also: seizures (dose-dependent), metabolic syndrome, myocarditis, sialorrhea. Lowest EPS risk |
| Quetiapine | Low D2 affinity; sedating | Commonly used in PD/DLB psychosis for practical ease + low D2 affinity, but efficacy data are mixed — "safest" is too strong. Pimavanserin is FDA-approved for PD psychosis; clozapine has strongest efficacy (ANC monitoring). DLB → all antipsychotics need caution (neuroleptic sensitivity + dementia mortality) |
| Aripiprazole | D2 partial agonist | Lowest metabolic/prolactin risk; may cause akathisia |
| Pimozide | First-gen D2 antagonist | FDA-approved for Tourette syndrome; QTc risk, requires ECG |
| Haloperidol | High-potency D2 antagonist | Highest EPS/NMS risk; IV form → QTc/torsades |
| Chlorpromazine | Low-potency; anticholinergic | More sedation/orthostasis, lower EPS; retinal deposits, blue-gray skin |
| Brexpiprazole (Rexulti) | D2 partial agonist + 5-HT1A partial agonist + 5-HT2A antagonist | FDA-approved 2023 for Alzheimer's-associated agitation (first FDA approval for this indication); also schizophrenia and adjunct in MDD |
Board Pearl
FDA boxed warning: antipsychotics increase mortality in elderly dementia patients (typical and atypical alike) — from cardiovascular events and infection. Use only when behavioral interventions fail and risks are clearly explained.
Board Pearl
Psychosis in PD/DLB requires careful selection — D2 blockade worsens parkinsonism. Pimavanserin (selective 5-HT2A inverse agonist, no D2 activity) is FDA-approved specifically for PD psychosis. Clozapine has the strongest efficacy data but requires ANC monitoring for agranulocytosis. Quetiapine is commonly used because of low D2 affinity and practical ease, but efficacy data are mixed — calling it "safest" is too strong. For DLB, all antipsychotics need caution (neuroleptic sensitivity + dementia mortality). Avoid high-potency D2 blockers (haloperidol, fluphenazine).
Drug-Induced Movement Disorders
Antipsychotic-Induced Movement Disorders by Time Course
| Disorder | Onset | Features | Treatment |
|---|---|---|---|
| Acute dystonia | Hours–days | Torticollis, oculogyric crisis, trismus, laryngospasm. Usually within 4–5 days of initiation or dose increase; young males, high-potency D2 blockers | Diphenhydramine or benztropine IM/IV |
| Akathisia | Days–weeks | Subjective restlessness, inability to sit still; often misdiagnosed as worsening psychosis | Propranolol (first-line), benzodiazepines |
| Parkinsonism | Days to weeks | Bradykinesia, rigidity, tremor — bilateral/symmetric (vs. asymmetric PD). DaT scan typically normal — but may be abnormal if the antipsychotic unmasked latent idiopathic PD | Reduce dose; benztropine or amantadine |
| Tardive dyskinesia | Months–years | Oro-bucco-lingual choreiform movements: lip smacking, tongue protrusion. May be irreversible. Risk factors: older age, female sex, African ancestry, mood disorder (vs schizophrenia), diabetes, cumulative antipsychotic exposure, prior EPS | VMAT2 inhibitors: valbenazine, deutetrabenazine (FDA-approved). Anticholinergics worsen TD |
Clinical Pearl
Anticholinergics (benztropine) treat acute dystonia and drug-induced parkinsonism but worsen tardive dyskinesia. VMAT2 inhibitors (valbenazine, deutetrabenazine) are the only FDA-approved TD treatments — distinguish from tetrabenazine, which is approved for Huntington chorea. Drug-induced parkinsonism is typically bilateral and symmetric (unlike asymmetric idiopathic PD), and DaT scan is normal (vs. abnormal in PD), helping differentiate the two.
Mood Stabilizers
Lithium
- First-line for bipolar disorder (mania + maintenance); anti-suicidal properties
- Narrow therapeutic index (0.6–1.2 mEq/L); toxicity at >1.5 mEq/L
- Neurologic: fine postural tremor at therapeutic levels (~50% of patients) — adverse, not therapeutic. Coarse tremor, ataxia, dysarthria, and irreversible cerebellar damage (SILENT — Syndrome of Irreversible Lithium-Effectuated NeuroToxicity) with toxicity
- Endocrine: hypothyroidism (up to 20%), hyperparathyroidism
- Renal: nephrogenic diabetes insipidus (ADH resistance at collecting duct)
- Teratogenicity: Ebstein anomaly (tricuspid valve malformation)
- Monitoring: lithium levels, TSH, creatinine, calcium
- Interactions: NSAIDs, thiazides, ACE inhibitors ↑ lithium levels; dehydration precipitates toxicity
Other Mood Stabilizers
| Drug | Bipolar Use | Board-Yield Points |
|---|---|---|
| Valproate | Acute mania | Neural tube defects (highest teratogenicity); fetal valproate syndrome: NTDs + reduced IQ + autism spectrum risk; hepatotoxic (children <2); contraindicated in mitochondrial disease; tremor, weight gain, hyperammonemia |
| Carbamazepine | Mania; maintenance | Autoinduction CYP3A4; hyponatremia (SIADH-like syndrome); SJS/TEN — screen HLA-B*1502 in Asian ancestry (Han Chinese, Thai, Malay) — boxed warning; HLA-A*3101 in Europeans/Japanese for hypersensitivity reactions; aplastic anemia |
| Lamotrigine | Bipolar depression | SJS/TEN (slow titration); valproate doubles levels; NOT for acute mania; no weight gain |
Board Pearl
Lithium toxicity is precipitated by dehydration, NSAIDs, thiazides, and ACE inhibitors. Coarse tremor with ataxia and confusion signals toxicity. Severe toxicity causes seizures, coma, and irreversible cerebellar damage. Hemodialysis if level >4.0 mEq/L (any patient), OR >2.5 mEq/L with severe neurologic symptoms / renal failure / hemodynamic instability (EXTRIP consensus).
Anxiolytics & Sedatives
Benzodiazepines
- Mechanism: GABA-A positive allosteric modulators — BZDs increase frequency of Cl− channel opening (saturable, ceiling effect); barbiturates increase duration of channel opening — no ceiling → more dangerous in overdose
- Examples: diazepam (long-acting), lorazepam (no active metabolites — preferred in liver disease), midazolam (ultra-short), clonazepam (anxiety/seizures)
- LOT mnemonic: Lorazepam, Oxazepam, Temazepam (LOT) — no active metabolites, preferred in hepatic disease/elderly
- Reversal: flumazenil — caution: can precipitate withdrawal seizures in chronic users
- Dependence: withdrawal can be life-threatening (seizures, delirium); requires gradual taper
Buspirone
- 5-HT1A partial agonist; used for GAD; takes 2–4 weeks for effect
- No sedation, no dependence, no withdrawal; does not impair cognition
- Ineffective for panic disorder; does not work if already tolerant to benzodiazepines
Dementia Medications
Cholinesterase Inhibitors & NMDA Antagonist
| Drug | Mechanism | Indication | Key Points |
|---|---|---|---|
| Donepezil | Reversible AChE inhibitor | Mild–severe AD | Most widely used; cholinergic side effects (nausea, diarrhea, bradycardia, vivid dreams) |
| Rivastigmine | AChE + BuChE inhibitor | Mild–moderate AD; PD dementia | Only ChEI with PD dementia indication; transdermal patch reduces GI side effects |
| Galantamine | AChE inhibitor + nicotinic allosteric modulator | Mild–moderate AD | Dual mechanism; similar side effects to donepezil |
| Memantine | NMDA antagonist | Moderate–severe AD | Blocks excitotoxicity; can combine with ChEIs; fewer GI effects |
Anti-Amyloid Monoclonal Antibodies
| Drug | Target | Key Points |
|---|---|---|
| Lecanemab | Amyloid-beta protofibrils | Early AD; IV q2 weeks; requires amyloid PET/CSF confirmation; 27% relative slowing of cognitive decline; absolute CDR-SB difference 0.45 points at 18 months (CLARITY-AD) |
| Donanemab | Pyroglutamate amyloid-beta | Early AD; dosing ends when amyloid cleared on PET |
| Aducanumab | Aggregated amyloid plaques | Controversial approval; largely withdrawn from market |
- ARIA-E: vasogenic edema/sulcal effusions (FLAIR hyperintensity) — ARIA-H: microhemorrhages/superficial siderosis (SWI/GRE)
- Symptomatic ARIA in ~3% (lecanemab); fatal ICH reported. ApoE4 homozygotes face higher rates of symptomatic/severe ARIA — caution per appropriate use recommendations; some now genotype before treatment
- Monitoring: serial brain MRIs required; most ARIA is asymptomatic
Clinical Pearl
Rivastigmine is the only ChEI FDA-approved for PD dementia in addition to AD. Its dual AChE + BuChE inhibition may provide additional benefit in DLB/PDD where BuChE activity increases as AChE decreases. The transdermal patch formulation significantly reduces the cholinergic GI side effects that limit oral dosing.
Clinical Pearl
Anti-amyloid mAbs and anticoagulation: Patients on anticoagulants were excluded from clinical trials. ARIA-H (microhemorrhages) can occur in up to 17% of treated patients, and concurrent anticoagulation may increase the risk of symptomatic intracerebral hemorrhage. ApoE4 genotyping is recommended before treatment — homozygotes have >35% ARIA risk and require careful risk-benefit discussion.
ADHD, Catatonia, Substance Use Disorders & Boxed Warnings
Stimulants & Non-Stimulants for ADHD
- Stimulants: methylphenidate, amphetamines — first-line; CV risks (HTN, tachycardia); growth suppression in children; abuse potential Schedule CII
- Non-stimulants: atomoxetine (NRI), viloxazine (SNRI/5-HT1A), guanfacine ER and clonidine ER (alpha-2 agonists)
ADHD + Tics — Agent Selection
| Agent | Class | Effect on tics | Caveat |
|---|---|---|---|
| Methylphenidate / amphetamine | Stimulant (DA/NE reuptake inhibitor) | May mildly & transiently worsen tics; not contraindicated in Tourette per AAN/TACT trial | CV/growth monitoring; Schedule CII |
| Atomoxetine | Non-stimulant selective NRI | Tic-neutral; preferred when tics severe or stimulant fails | FDA boxed warning: suicidality in adolescents; hepatotoxicity (rare) |
| Guanfacine ER / Clonidine ER | α2-adrenergic agonists | Reduce both ADHD symptoms AND tics — preferred when comorbid Tourette | Sedation, hypotension; clonidine: sleep architecture changes |
Functional Neurologic, Factitious, Malingering & Somatic Disorders
| Disorder | Symptom production | Motivation | Board clue |
|---|---|---|---|
| Malingering | Intentional (conscious) | External secondary gain (drugs, disability, avoiding prison/military duty) | Symptoms inconsistent & resolve once incentive removed; uncooperative with workup |
| Factitious disorder (Munchausen / "imposed on self") | Intentional | Internal — assume the sick role | Medical sophistication; multiple admissions, multiple providers; willing to undergo invasive testing |
| Factitious disorder imposed on another (Munchausen by proxy) | Intentional (in caregiver) | Caregiver gains sick-role attention via the victim | Child with unexplained recurrent illness that resolves when caregiver is separated — mandatory CPS report |
| Functional Neurologic / Conversion Disorder | Unintentional (not consciously produced) | None — psychological stressor often present but not required for diagnosis | Positive bedside signs: Hoover (hip extension recruits with contralateral hip flexion), tremor entrainment, give-way weakness, "drift without pronation"; symptoms inconsistent across exams |
| Somatic Symptom Disorder | Unintentional | None | Excessive thoughts/anxiety/behaviors about real OR perceived symptoms for >6 months |
| Illness Anxiety Disorder (formerly hypochondriasis) | Unintentional | None | Preoccupation with having/acquiring serious illness despite minimal symptoms; high reassurance-seeking |
💎 Board Pearl — FND
- The diagnosis of FND is “rule-in” (positive signs), not “rule-out.” Hoover sign and tremor entrainment in clinic are diagnostic — do not require extensive imaging.
- Conversion is not consciously produced; if the patient is consciously producing & gaining externally → malingering; consciously producing & gaining sick role → factitious.
Catatonia
- Lorazepam first-line (high doses up to 20 mg/d)
- ECT if benzodiazepine-refractory or malignant catatonia
- Antipsychotics may worsen catatonia or precipitate NMS — use cautiously
Substance Use Disorder Pharmacotherapy
| Disorder | Approved / Used Agents |
|---|---|
| Alcohol use disorder | Naltrexone (PO / Vivitrol IM), acamprosate (post-detox), disulfiram; gabapentin (off-label), topiramate (off-label) |
| Opioid use disorder | Methadone, buprenorphine/naloxone, naltrexone; naloxone (Narcan) for overdose reversal |
| Tobacco use disorder | Varenicline, bupropion, NRT (nicotine replacement therapy) |
Board Pearl — FDA Boxed Warnings
- Antipsychotics (typical & atypical): increased mortality in elderly dementia patients
- SSRIs/SNRIs: increased suicidality in patients <25 years old
- Carbamazepine: SJS/TEN in HLA-B*1502+ patients (Asian ancestry)
- Clozapine: severe neutropenia, myocarditis, seizures, orthostatic hypotension
- Nefazodone: hepatotoxicity
- Bupropion: neuropsychiatric (historical) — contraindicated in seizure disorders and eating disorders
Quick Reference
Psychopharmacology — At a Glance
| Drug / Class | Key Association | Board-Yield Feature |
|---|---|---|
| Citalopram | QTc prolongation | Max 40 mg/day; 20 mg if >60 years |
| Paroxetine | Most anticholinergic SSRI | Worst in pregnancy; worst withdrawal |
| Duloxetine | Neuropathic pain SNRI | Diabetic neuropathy, fibromyalgia |
| TCA overdose | QRS widening + seizures | Sodium bicarbonate |
| MAOIs | Tyramine crisis; cheese/wine | 2-week washout; serotonin syndrome with SSRIs |
| Serotonin syndrome | Clonus + hyperreflexia | Hours onset; cyproheptadine |
| NMS | Rigidity + elevated CK | Days–weeks; dantrolene + bromocriptine |
| Clozapine | Agranulocytosis; ANC monitoring | Most effective for refractory schizophrenia |
| PD psychosis | Pimavanserin (FDA-approved); clozapine (strongest efficacy, ANC monitoring); quetiapine (commonly used, mixed efficacy — not "safest") | DLB → all antipsychotics need caution (neuroleptic sensitivity + dementia mortality); AVOID haloperidol |
| Pimozide | Tourette syndrome | QTc risk; requires ECG |
| Tardive dyskinesia | Months–years; oro-bucco-lingual | Valbenazine, deutetrabenazine (VMAT2 inhibitors) |
| Lithium | Narrow index; tremor | Hypothyroidism, nephrogenic DI, Ebstein anomaly |
| Lamotrigine | Bipolar depression | SJS/TEN; valproate doubles levels |
| Benzodiazepines | GABA-A; ↑ frequency | Flumazenil reversal; withdrawal seizures |
| Buspirone | 5-HT1A partial agonist | No sedation, no dependence; GAD only |
| Donepezil | AChE inhibitor | Most widely used ChEI; mild–severe AD |
| Memantine | NMDA antagonist | Moderate–severe AD; blocks excitotoxicity |
| Lecanemab | Anti-amyloid mAb | ARIA-E/H monitoring; ApoE4 increases risk |
References
- Ropper AH, Samuels MA, Klein JP, Prasad S. Adams and Victor’s Principles of Neurology. 12th ed. McGraw-Hill; 2023.
- Stahl SM. Stahl’s Essential Psychopharmacology. 5th ed. Cambridge University Press; 2021.
- Bhatt A. Ultimate Review for the Neurology Boards. 3rd ed. Demos Medical; 2016.
- Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112–1120.
- Hauser RA, et al. KINECT 3: valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174(5):476–484.
- van Dyck CH, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9–21.
- Aminoff MJ, Greenberg DA, Simon RP. Clinical Neurology. 11th ed. McGraw-Hill; 2021.
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