Psychiatry System
Psychiatry
High-yield psychiatry for USMLE Step 2/3 — mood disorders, antipsychotics, anxiety spectrum, substance withdrawal, hyperthermic drug reactions, and personality disorders, extracted from Divine Intervention and organized for exam performance.
Mood Disorders
MDD and bipolar disorder share the depressive presentation but diverge critically at treatment — SSRIs can unmask mania in a bipolar patient. Master SIGECAPS, know which antidepressants avoid sexual dysfunction, and understand why lithium requires monitoring. Psychiatric timelines are the formula-driven shortcut that turns DSM questions into free points.
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Major Depressive Disorder & Antidepressant Pharmacology
- SIGECAPS diagnostic criteria: Sleep disturbance, loss of Interest, Guilt/worthlessness, low Energy, poor Concentration, Appetite change, Psychomotor retardation/agitation, Suicidal ideation — plus depressed mood = 9 total. Diagnosis = 5+ symptoms for >2 weeks
- First-line pharmacotherapy: SSRIs or SNRIs. Side effect that's useful: sexual dysfunction → use to treat premature ejaculation. Switch to bupropion (NDRI) or mirtazapine if sexual dysfunction is limiting adherence
- Bupropion (NDRI): No sexual dysfunction, helps smoking cessation + weight loss. Major contraindication: lowers seizure threshold — avoid in anorexia/bulimia, active alcohol withdrawal, seizure disorder
- SSRIs in special populations: Paroxetine contraindicated in pregnancy (fetal pulmonary hypertension). Fluoxetine = longest half-life, no discontinuation syndrome. Sertraline = preferred in pregnancy. Citalopram = QT prolongation risk (avoid post-MI)
- ECT: When MDD is refractory or patient is actively suicidal with no response to medications. Safe in pregnancy. Amnesia (retrograde + anterograde) is the main side effect — usually resolves
- Bipolar trap: If you catch a bipolar patient in a depressive episode and give SSRIs without a mood stabilizer, you can trigger mania. Always look for a manic episode in the history before diagnosing MDD
Antidepressant Comparison Table
| Drug / Class | Mechanism | Key Side Effects | Special Uses / Notes |
|---|---|---|---|
| SSRIs (fluoxetine, sertraline, paroxetine, citalopram, escitalopram) | Block serotonin reuptake transporter | Sexual dysfunction, GI upset, SSRI discontinuation syndrome (except fluoxetine) | First-line depression, anxiety, OCD, PTSD, bulimia. Sertraline preferred in pregnancy. Paroxetine avoided in pregnancy |
| SNRIs (venlafaxine, duloxetine) | Block serotonin + norepinephrine reuptake | Hypertension, sexual dysfunction, discontinuation syndrome | Avoid in pheochromocytoma or severe hypertension. Duloxetine also for diabetic neuropathy, fibromyalgia |
| Bupropion (NDRI) | Blocks NE + dopamine reuptake | Lowers seizure threshold, dry mouth, insomnia | No sexual dysfunction. Smoking cessation, weight loss. Contraindicated: seizure disorder, eating disorders, alcohol withdrawal |
| Mirtazapine | Alpha-2 antagonist → increases NE and serotonin release | Weight gain, sedation | Helpful when patient needs appetite stimulation + sleep improvement. No sexual dysfunction |
| MAOIs (phenelzine, tranylcypromine, isocarboxazid) | Inhibit monoamine oxidase → more serotonin, NE, dopamine | Hypertensive crisis with tyramine, serotonin syndrome | Atypical depression (hypersomnia, hyperphagia, leaden paralysis, rejection sensitivity) — MAOI preferred. 2-week washout before switching |
| TCAs (amitriptyline, imipramine, clomipramine) | Block serotonin + NE reuptake; also block Na channels, alpha-1, H1, muscarinic receptors | Anticholinergic (urinary retention, constipation, dry mouth), orthostatic hypotension, QRS widening (sodium channel blockade) | TCA overdose = wide QRS → treat with sodium bicarb. Clomipramine = 2nd-line OCD. Imipramine = enuresis in children |
Sleep Architecture in Depression
Patients with MDD have decreased REM latency (reach REM faster) and increased total REM sleep. This same pattern occurs in narcolepsy. Anxious/depressed patients also have elevated cortisol — expect ↑ cortisol on labs in depression vignettes.
MAOI Tyramine Crisis
Monoamine oxidase normally breaks down tyramine (a sympathomimetic found in aged cheese, red wine, cured meats). On an MAOI: tyramine accumulates → massive catecholamine release → hypertensive crisis. Treatment: phentolamine (alpha blocker) or nitroprusside. This same mechanism applies to linezolid — it is also an MAOI and carries the same tyramine warning.
Organic Causes of Depression
- Hypothyroidism — check TSH in all new depression presentations
- Beta blockers — medication-induced depression
- Interferon-alpha — used for hepatitis C, causes depression
- Antipsychotics — via hyperprolactinemia → erectile dysfunction → depression
- Left MCA stroke — strong association with post-stroke depression
- Acute intermittent porphyria — dark/port-wine urine + abdominal pain + neuropsychiatric symptoms
Mood Stabilizers for Bipolar Disorder
| Drug | Mechanism | Key Toxicities / Monitoring |
|---|---|---|
| Lithium | Inhibits IP3/DAG signaling; reduces neuronal excitability | Nephrogenic DI (lithium blocks ADH response → polyuria), hypothyroidism, tremor, Ebstein's anomaly in pregnancy. Narrow therapeutic window — monitor levels. Toxicity: coarse tremor, confusion, ataxia |
| Valproic acid | Blocks Na channels + increases GABA | Hepatotoxicity (monitor LFTs), teratogen (neural tube defects — give folic acid), thrombocytopenia, weight gain, pancreatitis |
| Lamotrigine | Blocks Na channels; reduces glutamate release | Stevens-Johnson syndrome (slow titration prevents this). Preferred mood stabilizer in pregnancy after valproate avoided |
| Carbamazepine | Blocks Na channels | Induces CYP450 (lowers other drug levels), agranulocytosis, SIADH, teratogen (neural tube defects) |
| Atypical antipsychotics (quetiapine, olanzapine, aripiprazole) | D2 + 5-HT2A block | Used for acute mania and as adjuncts. Metabolic syndrome risk |
Persistent Depressive Disorder vs Cyclothymia
Persistent depressive disorder (dysthymia): Low-grade depression for >2 years in adults (>1 year in children/adolescents). Does not meet full MDD criteria at any point. Treat with SSRIs.
Cyclothymia: Cycling between subsyndromal depression and hypomania for >2 years (not meeting full bipolar I/II criteria). No symptom-free period >2 months. Think of it as bipolar lite.
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HY Psychiatric Timelines — DSM Criteria You Must Know
- Acute stress disorder vs PTSD: Symptoms after trauma for <1 month = acute stress disorder. More than 1 month = PTSD. Both require identifiable trauma trigger
- Adjustment disorder: Stressor + depression/anxiety-lite (does not meet full criteria for MDD/GAD). Stressor must have ended less than 6 months ago. Symptoms do not persist beyond 6 months after stressor ends
- GAD duration: Worry about multiple life domains for >6 months. If it's been less, it's not GAD by DSM
- Schizophrenia spectrum: Hallucinations/delusions <1 month = brief psychotic disorder. 1–6 months = schizophreniform disorder. >6 months = schizophrenia
- Bipolar I vs II: Bipolar I = mania lasting >1 week (or any duration requiring hospitalization). Bipolar II = hypomania lasting >4 days. Mania = social/occupational dysfunction; hypomania = milder, no dysfunction
- ADHD / conduct disorder: ADHD diagnosed before age 12, symptoms in >2 settings. Conduct disorder = antisocial behavior under age 18 (criminal activity, aggression). After 18 = antisocial personality disorder
Master Timeline Table
| Diagnosis | Duration Threshold | Key Distinguishing Feature |
|---|---|---|
| Acute Stress Disorder | <1 month after trauma | Same symptoms as PTSD but time-limited; trauma trigger required |
| PTSD | >1 month after trauma | Intrusive thoughts, avoidance, hyperarousal, negative cognitions; treat with SSRIs + prazosin for nightmares |
| Adjustment Disorder | Stressor ended <6 months ago; symptoms <6 months after stressor ends | Sub-threshold anxiety or depression after identifiable stressor; does not meet full MDD/GAD criteria |
| MDD | >2 weeks | 5+ of 9 SIGECAPS criteria; depressed mood or anhedonia required |
| Persistent Depressive Disorder | >2 years (adults); >1 year (children) | Chronic low-level depression; never met full MDD criteria |
| GAD | >6 months | Multiple domains of worry; not just one specific trigger |
| Panic Disorder | Recurrent attacks + >1 month fear of future attacks | No identifiable trigger; attacks come "out of nowhere" |
| Specific Phobia | >6 months | One specific trigger; avoid related objects/situations; treat with CBT |
| Brief Psychotic Disorder | <1 month | Positive symptoms only; full recovery expected |
| Schizophreniform | 1–6 months | Symptoms of schizophrenia; may or may not recover fully |
| Schizophrenia | >6 months | Positive + negative symptoms; prodromal phase often included |
| Bipolar I Mania | >1 week (or hospitalized) | Full mania = social/occupational dysfunction |
| Bipolar II Hypomania | >4 days | Elevated mood without dysfunction; never met criteria for full mania |
| Cyclothymia | >2 years; no >2-month symptom-free gap | Subsyndromal cycling; does not meet bipolar I or II full criteria |
| Conduct Disorder | Under age 18 | Criminal behavior, aggression; adult version = antisocial personality |
| ADHD | Onset before age 12 | Symptoms in 2+ settings; combined hyperactive + inattentive subtypes |
Postpartum Blues vs Depression
Postpartum blues: Within 2 weeks of delivery, does not meet full MDD criteria — reassure and observe.
Postpartum depression: Meets 5+ of 9 SIGECAPS for >2 weeks after delivery — treat with SSRIs (brexanolone for severe/refractory cases, a neuroactive steroid administered IV).
Postpartum psychosis: Rare, psychiatric emergency — hallucinations, delusions; risk of infanticide; hospitalize and treat with antipsychotics + mood stabilizers.
Psychotic Disorders & Antipsychotics
The key to antipsychotic questions is knowing which generation the drug is and predicting its side effect profile from its receptor pharmacology. First-generation (typical) antipsychotics block D2 strongly — causing EPS and hyperprolactinemia but not metabolic syndrome. Second-generation (atypical) antipsychotics add 5-HT2A block — reducing EPS but adding metabolic risk. Clozapine is the outlier in everything.
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Antipsychotic Pharmacology — 1st vs 2nd Generation, Side Effects
- 1st-gen (typical) antipsychotics: Haloperidol, chlorpromazine, fluphenazine. Mechanism: D2 blockade. Best for positive symptoms (hallucinations, delusions). Not effective for negative symptoms
- EPS from D2 blockade (4 syndromes): Acute dystonia (hours–days, treat with benztropine or diphenhydramine), akathisia (subjective restlessness, treat with propranolol or benztropine), parkinsonism (weeks, reduce dose or switch), tardive dyskinesia (months–years, irreversible, treat with valbenazine or deutetrabenazine)
- Hyperprolactinemia from D2 blockade: Dopamine normally inhibits prolactin release. D2 blockade → ↑ prolactin → galactorrhea, amenorrhea, gynecomastia, sexual dysfunction. More prominent with risperidone among atypicals
- 2nd-gen (atypical) antipsychotics: Olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone. Mechanism: D2 + 5-HT2A blockade. Effective for positive AND negative symptoms. Less EPS but more metabolic side effects
- Metabolic syndrome risk: Olanzapine and quetiapine are worst. Weight gain, hyperglycemia, dyslipidemia. Ziprasidone and aripiprazole are metabolically neutral
- Clozapine: Reserved for treatment-resistant schizophrenia (failed 2 antipsychotics). Unique side effect: agranulocytosis — requires weekly CBC monitoring. Also causes seizures, myocarditis, excessive salivation. No tardive dyskinesia
EPS Timeline — The 4 Syndromes
| Syndrome | Onset | Presentation | Treatment |
|---|---|---|---|
| Acute Dystonia | Hours to days | Sustained muscle spasm — torticollis, oculogyric crisis, opisthotonos. Painful and alarming | Benztropine (anticholinergic) or diphenhydramine (IV/IM for acute) |
| Akathisia | Days to weeks | Subjective inner restlessness; patient cannot sit still, constantly moving legs. Distinguish from anxiety | Propranolol (first-line), benztropine, reduce dose |
| Drug-Induced Parkinsonism | Weeks | Bradykinesia, cogwheel rigidity, resting tremor, masked facies — mimics Parkinson's disease | Reduce antipsychotic dose, switch to atypical, or add benztropine. Levodopa is NOT used |
| Tardive Dyskinesia | Months to years | Involuntary choreiform movements — lip smacking, tongue protrusion, facial grimacing, writhing limbs. Irreversible in many | Valbenazine or deutetrabenazine (VMAT2 inhibitors). Stop offending agent if possible. Prevention is key |
Antipsychotic Receptor Profiles
| Drug | Key Receptors Blocked | Notable Side Effects | Clinical Notes |
|---|---|---|---|
| Haloperidol | D2 (very high affinity) | High EPS, high hyperprolactinemia, low sedation, low anticholinergic | High-potency typical. IV form for acute agitation in delirium. Also used for Tourette's |
| Chlorpromazine | D2, H1, alpha-1, muscarinic | Sedation, orthostatic hypotension, anticholinergic, low EPS | Low-potency typical. Corneal deposits, pigmentary retinopathy at high doses |
| Risperidone | D2 + 5-HT2A (strong D2) | High hyperprolactinemia among atypicals; moderate EPS | Highest prolactin elevation of all atypicals; no metabolic syndrome from D2 effect |
| Olanzapine | D2, 5-HT2A, H1, muscarinic | Highest weight gain + metabolic syndrome. Low EPS, low prolactin | Also approved for bipolar mania. Avoid in diabetes |
| Quetiapine | D2 (weak), 5-HT2A, H1 | Sedation, metabolic syndrome. Minimal EPS, minimal prolactin elevation | Off-label insomnia/anxiety. Cataracts reported (slit-lamp exam recommended) |
| Aripiprazole | D2 partial agonist + 5-HT1A partial agonist | Activating (insomnia, agitation). Minimal metabolic, minimal prolactin, minimal EPS | Metabolically neutral. Akathisia common. Also used for augmentation in MDD |
| Ziprasidone | D2 + 5-HT2A | QTc prolongation (avoid with other QT-prolonging drugs) | Metabolically neutral. Must be taken with food for absorption |
| Clozapine | D4, 5-HT2A, muscarinic, H1, alpha-1 | Agranulocytosis (weekly CBC required), seizures, myocarditis, hypersalivation, extreme sedation, metabolic syndrome | Only for treatment-resistant schizophrenia (failed 2+ antipsychotics). No tardive dyskinesia. No EPS |
Clozapine Monitoring Protocol
Clozapine requires ANC (absolute neutrophil count) monitoring — weekly for 6 months, then every 2 weeks for 6 months, then monthly. If ANC falls below 1500/mm³, hold clozapine. If below 500/mm³ (agranulocytosis), stop permanently. The patient should never receive clozapine again after agranulocytosis.
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Schizophrenia Spectrum — Symptoms, Diagnosis, Management
- Positive symptoms (dopamine excess in mesolimbic pathway): Hallucinations, delusions, disorganized speech, disorganized behavior — respond well to typical and atypical antipsychotics
- Negative symptoms (dopamine deficiency in mesocortical pathway): Flat affect, alogia, avolition, anhedonia, asociality — only atypical antipsychotics address these; typical antipsychotics worsen them
- Schizophrenia duration rule: >6 months total illness (including prodromal phase) with active psychosis >1 month. Two or more of: hallucinations, delusions, disorganized speech, disorganized behavior, negative symptoms
- Schizoaffective disorder: Schizophrenia + major mood episode (depressive or manic). Mood episode present for majority of illness duration. Treat the mood component (lithium, antidepressant) + antipsychotic
- Delusional disorder: Fixed, non-bizarre delusions for >1 month. No hallucinations, no significant functional impairment. Functioning otherwise intact. No antipsychotic required in many cases
- Long-acting injectables (LAI): Use when adherence is a major concern — haloperidol decanoate (monthly), paliperidone palmitate, aripiprazole lauroxil. Prevents relapse due to missed oral doses
Dopamine Pathway Framework
| Pathway | Function | In Schizophrenia | Antipsychotic Effect |
|---|---|---|---|
| Mesolimbic (VTA → limbic) | Reward, emotion, motivation | Overactive → positive symptoms (hallucinations, delusions) | D2 block → reduces positive symptoms |
| Mesocortical (VTA → prefrontal cortex) | Executive function, working memory, cognition | Underactive → negative symptoms, cognitive deficits | D2 block worsens negative symptoms (typical > atypical) |
| Nigrostriatal (SNc → striatum) | Motor control | Normal | D2 block → EPS (parkinsonism, dystonia, TD) |
| Tuberoinfundibular (hypothalamus → pituitary) | Prolactin inhibition | Normal | D2 block → hyperprolactinemia |
When to Use Which Antipsychotic
First episode: Atypical antipsychotic (risperidone, olanzapine, aripiprazole) — better tolerability, efficacy for both symptom domains.
Acute agitation / IM route needed: Haloperidol IM + lorazepam IM.
Treatment-resistant (>2 failed antipsychotics): Clozapine — monitor ANC weekly.
Poor adherence: Long-acting injectable (paliperidone palmitate, aripiprazole lauroxil).
Comorbid bipolar: Quetiapine, olanzapine, aripiprazole — all FDA-approved for bipolar.
Schizophrenia Spectrum — Differential
| Diagnosis | Duration | Stressor | Mood Episodes |
|---|---|---|---|
| Brief Psychotic Disorder | <1 month | May follow significant stressor | None required |
| Schizophreniform | 1–6 months | None required | None required |
| Schizophrenia | >6 months | None required | None (if present, must be brief) |
| Schizoaffective | >6 months | None required | Present for majority of illness |
| Bipolar with psychotic features | Variable | None required | Psychosis only during mood episodes |
| Delusional Disorder | >1 month | None required | None. Non-bizarre delusions only. Function intact |
Anxiety, Trauma & OCD
The anxiety spectrum is differentiated by trigger specificity, duration, and functional impairment. The NBME loves distractor answer choices between specific phobia, panic disorder, GAD, and PTSD — all of which share symptoms of fear and autonomic arousal. The key: panic attacks have no identifiable trigger; specific phobia has one trigger; GAD has many; PTSD requires prior trauma.
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Specific Phobia, GAD, PTSD & Panic Disorder — The Differentiating Framework
- Specific phobia vs GAD: Specific phobia = one trigger (one thing), symptoms >6 months, severe distress/avoidance. GAD = multiple life domains, >6 months — not focused on one thing. Best treatment for specific phobia: CBT (exposure therapy/systematic desensitization). Exception: infrequent trigger → short-acting benzodiazepine
- Panic attack vs panic disorder: Panic attack = no identifiable trigger — patient cannot explain why it happened. If there IS an identifiable trigger, it's not a panic attack. Panic disorder = recurrent attacks + >1 month worry about having another attack
- PTSD differentiation: Always requires an identifiable prior trauma (violence, military, rape, first responder experience). Symptoms: intrusive thoughts, avoidance, hyperarousal, negative cognitions. Treat with SSRIs (first-line) + prazosin for nightmares
- OCD: Obsessions (intrusive, ego-dystonic thoughts) + compulsions (repetitive behaviors to reduce anxiety). First-line: SSRIs. If SSRI fails, add clomipramine (TCA, strongest serotoninergic TCA, 2nd line for OCD). Adjunct: CBT with exposure and response prevention (ERP)
- GAD treatment: SSRIs and SNRIs (first-line), buspirone (5-HT1A partial agonist, takes weeks to work — not for acute anxiety), benzodiazepines (for acute/short-term), pregabalin (Europe-preferred)
- Social anxiety disorder: Fear of social situations and judgment; avoid public speaking, eating in public. Treat with SSRIs (long-term). Beta blockers (propranolol) for situational/performance anxiety (before specific events)
Anxiety Differential — NBME Differentiator Table
| Disorder | Trigger | Duration | Scope of Worry | Trauma History? | Treatment |
|---|---|---|---|---|---|
| Specific Phobia | One specific thing (dog, blood, flying) | >6 months | Single domain | No (no trauma from it) | CBT/exposure; benzo if infrequent trigger |
| Social Anxiety | Social situations, evaluation by others | >6 months | Social/performance domain | No | SSRIs; propranolol for performance-only |
| Panic Disorder | No identifiable trigger | >1 month of worry between attacks | Any — unprovoked | No | SSRIs; benzos (short-term); CBT |
| GAD | Multiple things (work, health, family) | >6 months | Multiple life domains | No | SSRIs/SNRIs, buspirone, benzos (short-term) |
| PTSD | Defined trauma event | >1 month post-trauma | Trauma-related | YES (required) | SSRIs; prazosin for nightmares; CBT/EMDR |
| Acute Stress Disorder | Defined trauma event | <1 month post-trauma | Trauma-related | YES (required) | Supportive; CBT; may prevent progression to PTSD |
| OCD | Internal obsessional thoughts | Variable | Specific obsessional theme | No | SSRIs (high dose); clomipramine; CBT with ERP |
Buspirone Pearls
Buspirone (5-HT1A partial agonist) is a second-line agent for GAD. Key facts: takes 2–4 weeks to work (not useful for acute anxiety), does not cause dependence or sedation, does not potentiate alcohol. Cannot be used PRN. It is also a mild serotonergic agent — can contribute to serotonin syndrome if combined with SSRIs or MAOIs.
OCD-Spectrum Disorders
| Disorder | Core Feature | Treatment |
|---|---|---|
| OCD | Ego-dystonic obsessions + compulsions; patient recognizes thoughts are irrational | SSRIs (high dose, e.g., fluoxetine 60–80mg); clomipramine 2nd line; CBT with ERP |
| Body Dysmorphic Disorder | Preoccupation with imagined physical defect; excessive grooming, mirror checking | SSRIs; CBT |
| Trichotillomania | Compulsive hair pulling → alopecia; hair on pathology shows broken shafts | CBT (habit reversal); clomipramine, SSRIs (less evidence) |
| Hoarding Disorder | Excessive acquisition of objects; inability to discard; significant impairment | CBT (specifically for hoarding); SSRIs |
Substance Use & Withdrawal
Intoxication and withdrawal questions require knowing the key differentiating features for each substance — what pupil size, what behavior, what vital signs, and critically, which withdrawals are life-threatening. Two withdrawals that kill: alcohol and benzodiazepines. Opioid withdrawal is miserable but rarely fatal. Cocaine and stimulant withdrawal is not dangerous.
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Alcohol, Opioid, Stimulant & Cannabis — Intoxication vs Withdrawal
- Alcohol intoxication: Disinhibition, slurred speech, ataxia, nystagmus. No respiratory depression (unlike opioids/benzos). Labs: AST > ALT (ratio 2:1 or more), ↑ GGT, hypoglycemia (↑ NADH → impairs gluconeogenesis + glycolysis)
- Alcohol withdrawal timeline: 6–24h: tremors, anxiety, tachycardia, hypertension; 12–24h: withdrawal seizures; 24–72h: alcoholic hallucinosis (visual/tactile hallucinations with intact orientation); 48–96h: delirium tremens (DTs) — confusion, agitation, autonomic instability, life-threatening
- Alcohol withdrawal treatment: Long-acting benzodiazepine (chlordiazepoxide or diazepam). CIWA scale to monitor severity. Always give thiamine BEFORE glucose. Naltrexone for ongoing use disorder (reduces craving)
- Opioid intoxication: CNS depression, bilateral pinpoint pupils (miosis), respiratory depression. Treat overdose with naloxone. Opioid withdrawal is miserable (diarrhea, lacrimation, piloerection, yawning, myalgia, diaphoresis) but not fatal
- Stimulant intoxication (cocaine/methamphetamine): Both: ↑BP, tachycardia, mydriasis (pupil dilation), hyperthermia. Cocaine = chest pain (MI risk, coronary vasospasm), pressured speech. Meth = prominent hallucinations, longer-lasting psychosis. Treat both with benzodiazepines
- Cannabis intoxication: Conjunctival injection, increased appetite, slow reaction time, relaxation. NOT: ataxia, slurred speech (unlike alcohol). Acute cannabis psychosis possible with high-potency THC
Intoxication vs Withdrawal Master Table
| Substance | Intoxication | Withdrawal | Fatal? | Treatment |
|---|---|---|---|---|
| Alcohol | Disinhibition, ataxia, slurred speech, no resp depression. Pupils: normal | 6h: tremor; 12–24h: seizures; 24–72h: hallucinations; 48–96h: DTs | YES (DTs, seizures) | Long-acting benzos (chlordiazepoxide, diazepam); thiamine before glucose; naltrexone or acamprosate for use disorder |
| Benzodiazepines | Similar to alcohol; respiratory depression; normal or depressed pupils. Treat OD with flumazenil | Identical to alcohol withdrawal; anxiety, seizures, DTs | YES | Long-acting benzo taper; flumazenil for acute OD only |
| Opioids | CNS depression, bilateral miosis (pinpoint), resp depression, constipation | "DAWG": Diarrhea, Anxiety, yawning/lacrimation, piloerection. Also myalgia, diaphoresis, insomnia | No (rarely) | Intox: naloxone. Withdrawal: clonidine (autonomic sx), methadone or buprenorphine/naloxone (MAT) |
| Cocaine | ↑BP, tachycardia, mydriasis, hyperthermia, chest pain/MI, pressured speech. No resp depression | Crash: fatigue, depression, hypersomnia, increased appetite. Not dangerous | No | Intox: benzodiazepines. Cocaine + beta-blockers: AVOID (unopposed alpha → hypertensive crisis). Use phentolamine or CCB for HTN |
| Methamphetamine | Like cocaine + prominent hallucinations (visual/tactile), more prolonged psychosis, dental erosion (meth mouth) | Fatigue, hypersomnia, increased appetite, depression | No | Intox: benzodiazepines. Antipsychotics for psychosis if persistent |
| Cannabis | Conjunctival injection, ↑appetite, slow reaction time, euphoria. No ataxia or slurred speech | Mild: irritability, insomnia, decreased appetite | No | Supportive. Cannabinoid hyperemesis: capsaicin cream, hot showers (counterintuitive but works) |
| PCP (Phencyclidine) | Violent behavior, nystagmus (horizontal AND vertical), analgesia, dissociation. Pupils: normal or large | Not clinically significant | No | Calm environment, benzos for agitation, avoid physostigmine |
| Hallucinogens (LSD) | Visual hallucinations, flashbacks (HPPD), synesthesia, no autonomic instability | Minimal | No | Supportive; benzos for acute panic |
Cocaine + Beta Blockers = Dangerous
Never give beta blockers to a patient with cocaine intoxication. Beta blockade leaves alpha-1 receptors unopposed → severe hypertension + coronary vasospasm. Use phentolamine (non-selective alpha blocker) or nitroglycerin for cocaine-induced chest pain. Benzodiazepines address the underlying adrenergic excess.
Wernicke–Korsakoff — Always Thiamine First
Wernicke encephalopathy: Acute triad — confusion, ophthalmoplegia (CN6 palsy → lateral gaze palsy), ataxia. Give IV thiamine immediately. If you give glucose first in a thiamine-depleted alcoholic, you deplete the remaining thiamine → precipitate Wernicke's.
Korsakoff syndrome: Chronic — anterograde amnesia (can't form new memories), confabulation, intact remote memory. Mamillary body atrophy on MRI. Often irreversible once established.
Medication-Assisted Treatment (MAT) for Opioid Use Disorder
| Drug | Mechanism | Key Points |
|---|---|---|
| Methadone | Full mu-opioid agonist (long-acting) | Dispensed daily at licensed clinic. Risk of QTc prolongation. High overdose risk if misused |
| Buprenorphine/Naloxone (Suboxone) | Partial mu agonist + naloxone (prevents IV abuse) | Can prescribe in office setting (X-waiver). Ceiling effect for respiratory depression. Preferred in pregnancy (buprenorphine monoproduct) |
| Naltrexone (Vivitrol) | Full opioid antagonist | Monthly IM injection. Must be opioid-free 7–10 days before starting. No opioid efficacy for pain |
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Substance Withdrawal Timelines & Sedative-Hypnotic Toxidrome
- Alcohol withdrawal seizures: Peak 12–24 hours after last drink. Grand mal, not focal. Do NOT wait for seizures — prophylax with long-acting benzodiazepine on admission (CIWA protocol)
- Delirium tremens (DTs): 48–96 hours after last drink. Autonomic storm (fever, tachycardia, diaphoresis, hypertension) + confusion + visual hallucinations. 5–15% mortality if untreated. Treat with IV benzodiazepines
- Opioid withdrawal timeline: Short-acting opioids (heroin): onset 8–24h, peak 36–72h, resolves 5–7 days. Long-acting (methadone): onset 36–48h, peak 72–96h, resolves 14–21 days. Clonidine reduces autonomic symptoms (lacrimation, diaphoresis, piloerection)
- Stimulant withdrawal: "Crash" phase — profound fatigue, depression, hypersomnia, carbohydrate craving. Not medically dangerous. No pharmacotherapy required. Resolve over days to weeks
- Nicotine withdrawal: Irritability, anxiety, difficulty concentrating, increased appetite, weight gain. Treat with varenicline (partial nicotinic agonist — most effective), bupropion, nicotine replacement
- Flumazenil caution: Reverses benzo intoxication acutely. Risk: precipitates benzo withdrawal in a benzo-dependent patient → seizures. Only use for acute OD in benzo-naive patients
Withdrawal Syndrome Comparison
| Substance | Onset After Last Use | Peak | Lethal? | Key Features |
|---|---|---|---|---|
| Alcohol | 6–24 hours | 48–96h (DTs) | YES | Tremors → seizures → alcoholic hallucinosis → DTs (autonomic storm + delirium) |
| Benzodiazepines | 12–24h (short-acting); 2–7 days (long-acting) | Variable | YES | Identical to alcohol withdrawal. Long-acting BZDs (diazepam): delayed, prolonged withdrawal |
| Heroin / short-acting opioids | 8–24 hours | 36–72 hours | Rarely | DAWG symptoms. Piloerection, lacrimation, yawning, GI upset, myalgia |
| Methadone / long-acting opioids | 36–48 hours | 72–96 hours | No | Same as above but delayed and prolonged (lasts 2–3 weeks) |
| Cocaine / stimulants | Hours after binge | 24–48 hours | No | Crash: depression, hypersomnia, fatigue, carb craving. Anhedonia may persist weeks |
| Nicotine | Hours | 24–72 hours | No | Irritability, anxiety, increased appetite, concentration difficulties |
Alcoholic Hallucinosis vs DTs — Critical Distinction
Alcoholic hallucinosis: Visual or tactile hallucinations with INTACT orientation and normal vitals. Occurs 12–48 hours after last drink. Patients know they are in the ER and are not confused. No autonomic instability.
Delirium tremens: Confusion + disorientation + autonomic instability (fever, HTN, tachycardia, diaphoresis). Occurs 48–96 hours. LIFE-THREATENING. Treat with IV benzodiazepines (lorazepam or diazepam).
Hyperthermic Drug Syndromes
Serotonin syndrome, NMS, and malignant hyperthermia form the most tested drug-reaction triad in psychiatry. They share fever and muscle rigidity — but the key differentiator is reflexes: serotonin syndrome = hyperreflexia + clonus (too much movement); NMS and malignant hyperthermia = lead-pipe rigidity + hypokinesia (no movement). Knowing the offending drugs for each prevents misdiagnosis.
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Serotonin Syndrome — Triggers, Presentation & Management
- Classic triad: Hyperthermia + hyperreflexia/clonus + hyperkinesia (agitation, tremor). The reflexes and hyperkinesis distinguish serotonin syndrome from NMS and malignant hyperthermia
- Classic drug combinations: SSRI + MAOI (never combine; 2-week washout required). SSRI + linezolid (linezolid is a 50S protein synthesis inhibitor AND a monoamine oxidase inhibitor). SSRI + tramadol, meperidine, dextromethorphan, St. John's Wort, sumatriptan, MDMA, methamphetamine
- Non-classic serotonergic agents (HY NBME integrations): Linezolid (MRSA/VRE coverage), methylene blue (methemoglobinemia treatment), meperidine (pancreatitis pain), tramadol, dextromethorphan (DM in cough syrups), cocaine, buspirone, sumatriptan, St. John's Wort
- Management steps: (1) Withdraw the offending agent immediately. (2) Supportive care. (3) Benzodiazepine IV (preferred over cyproheptadine — IV route, faster onset, 100% bioavailability). (4) Cyproheptadine PO (serotonin receptor antagonist) if benzo insufficient. (5) Active cooling if hyperthermic
- Linezolid + SSRI integration: Patient has endocarditis (MRSA/VRE) started on linezolid while on an SSRI → develops fever, hyperreflexia, agitation → serotonin syndrome. Also: linezolid + tyramine-rich foods → hypertensive crisis (same as MAOI rule)
- Autonomic features: Tachycardia, mydriasis, diaphoresis — from secondary norepinephrine elevation when serotonin surges. Rhabdomyolysis (myoglobinuria → red urine) can occur in severe cases
Drugs That Can Cause Serotonin Syndrome
| Category | Examples | Mechanism |
|---|---|---|
| SSRIs | Fluoxetine, sertraline, paroxetine, citalopram, escitalopram | Block serotonin reuptake transporter (SERT) |
| SNRIs | Venlafaxine, duloxetine | Block SERT + NET |
| MAOIs | Phenelzine, tranylcypromine, isocarboxazid | Inhibit MAO → less serotonin degradation |
| Non-classic MAOIs | Linezolid (antibiotic), methylene blue (methemoglobinemia Rx) | Also inhibit MAO — HY NBME integration drugs |
| TCAs | Clomipramine, imipramine (highest serotonergic among TCAs) | Block SERT + NE reuptake |
| Opioids | Tramadol, meperidine, dextromethorphan (DM) | Weak SERT inhibition or serotonin release |
| Stimulants/Drugs of Abuse | Cocaine, MDMA (ecstasy), methamphetamine | Increase serotonin release from presynaptic terminals |
| Migraine medications | Sumatriptan, other triptans | 5-HT1B/1D agonists |
| Anxiolytics | Buspirone | 5-HT1A partial agonist |
| Herbal supplements | St. John's Wort | Weak SSRI activity; also induces CYP450 (↓OCP efficacy) |
| Antiemetics | Metoclopramide | D2 blocker + weak serotonergic activity |
Benzo Before Cyproheptadine — Why
In acute serotonin syndrome the patient is hemodynamically unstable, agitated, and often cannot take PO medications. Benzodiazepines can be given IV, have 100% bioavailability, and act within minutes. Cyproheptadine (a 5-HT receptor antagonist — the definitive antidote) is only available in oral form → slower onset, first-pass metabolism, difficult to administer to a vomiting agitated patient. Use benzos first; add cyproheptadine once the patient can tolerate PO.
Serotonin Syndrome vs Other Hyperthermic Syndromes
| Feature | Serotonin Syndrome | NMS | Malignant Hyperthermia |
|---|---|---|---|
| Cause | Too much serotonin (two serotonergic drugs) | D2 blockade or dopamine agonist withdrawal | Volatile anesthetics or succinylcholine in susceptible patient (RYR1 mutation) |
| Reflexes | HYPERREFLEXIA, clonus | Lead-pipe rigidity; HYPOKINESIA | Severe rigidity; HYPOKINESIA |
| Onset | Rapid (hours) | Slow (days to weeks after starting drug) | Immediate (during anesthesia) |
| Muscle finding | Tremor, myoclonus, hyperkinesis | Lead-pipe rigidity | Masseter spasm → generalized rigidity |
| Pupils | Mydriasis (adrenergic surge) | Variable | Variable |
| Treatment | Withdraw drug, benzos, cyproheptadine, cooling | Withdraw drug, dantrolene, bromocriptine, benzos, cooling | Stop anesthetic, dantrolene, cooling |
| Rhabdomyolysis | Yes (severe cases) | Yes | Yes (hyperkalemia, hypocalcemia, hyperphosphatemia) |
EP452
NMS & Malignant Hyperthermia — Pathophysiology, Treatment & Differentiators
- NMS causes — two pathways: (1) D2 blockade by antipsychotics (haloperidol, chlorpromazine, metoclopramide, droperidol). (2) Abrupt withdrawal of a dopamine agonist — levodopa in Parkinson's, bromocriptine for prolactinoma. Both → sudden loss of dopaminergic tone in striatum → lead-pipe rigidity, hyperthermia
- NMS presentation: "FALTER" — Fever, Altered mental status, Lead-pipe rigidity, Tachycardia, Elevated CK (rhabdomyolysis), Respiratory failure. Develops over days to weeks (unlike serotonin syndrome which is rapid)
- NMS treatment: Stop offending agent. Dantrolene (ryanodine receptor antagonist → decreases calcium release → reduces muscle rigidity). Bromocriptine (dopamine agonist — counters D2 blockade). Benzodiazepines for agitation. Active cooling
- Malignant hyperthermia trigger: Susceptible patients (autosomal dominant RYR1 mutation) exposed to volatile anesthetics (halothane, sevoflurane, desflurane, isoflurane, enflurane) or succinylcholine → massive calcium release from sarcoplasmic reticulum → hyperthermia, rigidity, rhabdomyolysis
- Malignant hyperthermia labs: Hyperkalemia (muscle cells lysing → K+ release), hypocalcemia (phosphate released from muscle binds Ca²⁺), hyperphosphatemia, metabolic acidosis (lactic acid from muscle hypercatabolism), ↑ CK, myoglobinuria (red/brown urine)
- Malignant hyperthermia treatment: Stop anesthetic immediately. Dantrolene IV (definitive treatment — ryanodine receptor antagonist). Active cooling. Monitor for acute kidney injury from myoglobinuria
NMS — Pathophysiology in Detail
Dopamine normally exerts an inhibitory effect on muscle tone via the nigrostriatal pathway. When D2 receptors are blocked (by antipsychotics like haloperidol, or metoclopramide) or when dopamine supply is abruptly removed (stopping levodopa or bromocriptine), the striatum becomes unregulated → massive muscle rigidity. This is why NMS is mechanistically the opposite of Parkinson's disease — the same pathway, different direction.
Non-Classic NMS Trigger — Dopamine Agonist Withdrawal
Bromocriptine is used to treat prolactinoma (dopamine agonist → inhibits prolactin). If a patient with prolactinoma misses doses or is abruptly stopped, they can develop NMS. Same principle: a Parkinson's patient who stops levodopa/carbidopa suddenly → NMS. This is a high-yield NBME integration because the trigger is not the classic antipsychotic.
Malignant Hyperthermia — Molecular Mechanism
The ryanodine receptor (RYR1) is a calcium-release channel on the sarcoplasmic reticulum. Normally, action potentials trigger controlled calcium release for muscle contraction. In RYR1 mutation carriers (autosomal dominant), volatile anesthetics and succinylcholine cause the mutant RYR1 to stay locked open → uncontrolled massive calcium release → sustained muscle contraction → heat generation + lactic acidosis + cell death.
Dantrolene is a ryanodine receptor antagonist — it blocks this calcium release channel, preventing the hypercalcemia that drives the hypercontractile state.
Metabolic Cascade in Malignant Hyperthermia
- Muscle hypermetabolism → ↑↑ heat → hyperthermia
- Anaerobic glycolysis in overworked muscles → lactic acidosis (high anion gap metabolic acidosis)
- Muscle cell death → ↑ CK, myoglobinuria → acute kidney injury
- K⁺ released from lysed cells → hyperkalemia → EKG changes (PVCs, VT/VF risk)
- Phosphate released from cells binds Ca²⁺ → hypocalcemia
Muscle Biopsy for Malignant Hyperthermia Susceptibility
The caffeine-halothane contracture test (CHCT) on a muscle biopsy is the gold-standard diagnostic test for malignant hyperthermia susceptibility. If a patient or family member has had a prior reaction to anesthesia, test them before any future anesthetic exposure. In susceptible patients: use non-triggering anesthetics (propofol, nitrous oxide, ketamine) and avoid succinylcholine.
Personality & Somatic Disorders
Personality disorders are ego-syntonic (the patient does not see a problem) by definition — unlike OCD or anxiety which are ego-dystonic. The three clusters follow predictable NBME patterns: Cluster A = odd/eccentric; Cluster B = dramatic/emotional (the board-testable ones); Cluster C = anxious/fearful. Somatic disorders differ in the presence or absence of conscious intent.
EP349
Personality Disorders, Somatic Symptom Disorder & Factitious Disorder
- Cluster A ("weird"): Paranoid (suspicious, mistrustful — no psychosis), Schizoid (voluntarily socially isolated, flat affect — content being alone), Schizotypal (magical thinking, odd beliefs, ideas of reference — does not meet schizophrenia threshold)
- Cluster B ("wild"): Antisocial (criminal behavior, disregard for others, must be >18 with conduct disorder history), Borderline (unstable identity, relationships, mood — splitting, self-harm, fear of abandonment, impulsivity), Histrionic (attention-seeking, dramatic, sexually provocative), Narcissistic (grandiosity, lack of empathy, requires admiration)
- Cluster C ("worried"): Avoidant (wants relationships but fears rejection — wants connection, unlike schizoid), Dependent (clinging behavior, cannot make decisions independently), Obsessive-Compulsive personality (perfectionism, rigidity, orderliness — ego-syntonic; DIFFERENT from OCD which is ego-dystonic)
- Borderline personality disorder treatment: Dialectical behavior therapy (DBT) — the only evidence-based therapy specifically designed for BPD. No medication approved; SSRIs or mood stabilizers may help comorbid symptoms
- Somatic symptom disorder: Real physical symptoms + excessive concern, time, and energy devoted to them. Not consciously faking. No identifiable medical cause OR even if cause exists, reaction is disproportionate. Treat with regular (not PRN) physician visits, CBT
- Factitious disorder vs malingering: Factitious (Munchausen) = consciously fabricates illness for sick role, NO external incentive (just wants to be a patient). Malingering = consciously fabricates for external gain (money, drugs, avoid prison). Factitious by proxy = caregiver fabricates illness in dependent person
Personality Disorder Cluster Summary
| Cluster | Disorder | Core Feature | Key Differentiator |
|---|---|---|---|
| A — Odd/Eccentric | Paranoid | Pervasive distrust, suspicious of others' motives | No psychosis (unlike schizophrenia); trust no one |
| Schizoid | Social detachment; prefers solitude; restricted affect | Does not want relationships — content alone (unlike avoidant) | |
| Schizotypal | Magical thinking, odd beliefs, ideas of reference, eccentric behavior | Does not meet criteria for schizophrenia; no persistent psychosis | |
| B — Dramatic/Emotional | Antisocial | Disregard for rights of others; criminal behavior, lack of remorse | Must be >18; conduct disorder must precede age 18 |
| Borderline | Unstable identity, relationships, affect; splitting; fear of abandonment; self-harm | Splitting (people are all-good or all-bad). DBT is treatment of choice | |
| Histrionic | Excessive emotionality, attention-seeking, dramatic, seductive | Wants to be center of attention; feels uncomfortable when not | |
| Narcissistic | Grandiosity, lack of empathy, requires admiration, sense of entitlement | Fragile under surface; rage when criticized | |
| C — Anxious/Fearful | Avoidant | Social inhibition, feelings of inadequacy, hypersensitive to rejection | Wants relationships but avoids due to fear — unlike schizoid who does not want them |
| Dependent | Excessive need to be taken care of; submissive, clinging; cannot make decisions | Goes to great lengths to obtain nurturing; difficulty initiating tasks independently | |
| OC Personality | Preoccupation with orderliness, perfectionism, control; inflexible; ego-syntonic | Ego-SYNTONIC (unlike OCD which is ego-dystonic); patient thinks their behavior is fine |
Somatic Disorders — Differentiating Table
| Disorder | Conscious Fabrication? | External Incentive? | Core Feature |
|---|---|---|---|
| Somatic Symptom Disorder | No | No | Real distress from physical symptoms; excessive worry, time, energy devoted to symptoms |
| Illness Anxiety Disorder (Hypochondriasis) | No | No | Preoccupation with having or acquiring a serious illness; minimal or no physical symptoms; reassurance provides only brief relief |
| Functional Neurological Disorder (Conversion) | No | No | Neurological symptoms (paralysis, blindness, seizures) with no neurological disease. La belle indifférence (apparent lack of concern about symptoms) |
| Factitious Disorder (Munchausen) | YES | No (internal — wants sick role) | Intentionally produces or feigns illness to be a patient. No secondary gain |
| Factitious by Proxy (Munchausen by proxy) | YES | No (wants caregiver role) | Caregiver fabricates or causes illness in a child/dependent. Child abuse — mandatory reporting |
| Malingering | YES | YES (external — money, drugs, avoid legal consequences) | Consciously fakes illness for clear external gain. Not a psychiatric diagnosis |
Conversion Disorder (Functional Neurological Symptom Disorder)
Classic vignette: patient with acute onset paralysis or blindness following significant psychosocial stressor, but no neurological lesion on imaging and normal nerve conduction studies. Key finding: la belle indifférence — the patient appears surprisingly unconcerned about a dramatic neurological deficit. Management: psychotherapy + PT/OT; do not confront the patient or tell them the symptoms are "fake."