Behavioral Health

First-episode psychosis: workup and management

Clinical Overview and When to Suspect First-Episode Psychosis

— Peak onset: late teens to mid-20s in men, slightly later (20s–30s) in women

— Lifetime prevalence of primary psychotic disorders ~3%; schizophrenia ~0.7%

— Bimodal female peak with a second rise in 40s

— Adolescent or young adult with new social withdrawal, declining school/work performance, sleep disruption, or "odd" beliefs

— Family or roommate brings the patient in; collateral often more revealing than self-report

— Acute behavioral change in any age group — but new psychosis after age 40 should heighten suspicion for secondary (medical, substance, neurologic) causes until proven otherwise

— Rule out delirium, substance intoxication/withdrawal, and acute neurologic disease

— Establish safety (suicide, homicide, command hallucinations, ability to care for self)

— Initiate Coordinated Specialty Care (CSC) referral — the evidence-based team model (NIMH RAISE trial) combining low-dose antipsychotics, psychotherapy, family education, supported employment/education, and case management

Definition: First-episode psychosis (FEP) refers to the initial presentation of psychotic symptoms — delusions, hallucinations, disorganized speech/behavior, or negative symptoms — regardless of underlying etiology

Epidemiology:

When to suspect FEP in clinic or ED:

Prodrome (attenuated psychosis): months to years of subthreshold symptoms — magical thinking, brief perceptual disturbances, suspiciousness, functional decline. Recognition matters because duration of untreated psychosis (DUP) predicts long-term outcome

Step 3 framing: FEP is a medical emergency-equivalent, not just a psychiatric label. Mandatory tasks:

Board pearl: New psychosis >40 yo, abnormal vitals, fluctuating sensorium, focal neuro signs, or autonomic instability → assume medical/neurologic etiology (delirium, autoimmune encephalitis, substance) and work it up before anchoring on schizophrenia. Primary psychotic disorders have a normal sensorium — clouded consciousness is delirium until proven otherwise

Presentation Patterns and Key History

— Delusions: persecutory most common; also referential, grandiose, somatic, religious, control/thought insertion

— Hallucinations: auditory predominate in primary psychotic disorders; visual, olfactory, or tactile hallucinations should prompt medical/substance workup

— Disorganized speech: tangentiality, loose associations, word salad

— Disorganized/catatonic behavior

— Timeline: prodrome duration, acute trigger, DUP

— Substance use: cannabis (especially high-potency, daily), methamphetamine, cocaine, hallucinogens, synthetic cannabinoids, PCP, alcohol withdrawal

— Medications: corticosteroids, stimulants, anticholinergics, dopamine agonists, interferon, isoniazid, levetiracetam

— Family history of psychosis, bipolar disorder, suicide

— Birth/developmental history, head injury, seizures

— Recent infections, autoimmune disease, thyroid symptoms

— Safety: SI/HI, command hallucinations, weapons access, prior violence, ability to eat/sleep/maintain hygiene

— Collateral from family — essential; patients with poor insight underreport

Positive symptoms (added experiences):

Negative symptoms (subtracted function): blunted affect, alogia, avolition, anhedonia, asociality — often the most disabling and treatment-resistant

Cognitive symptoms: impaired attention, working memory, processing speed — present before frank psychosis

Key history to obtain (and document):

Mood overlay: screen for manic and depressive episodes — distinguishes schizoaffective disorder and psychotic mood disorders from schizophrenia

Key distinction: Mood-congruent psychotic features during a mood episode = psychotic mood disorder. Psychosis persisting ≥2 weeks without prominent mood symptoms = schizoaffective disorder or schizophrenia spectrum. Psychosis only during mood episodes ≠ schizoaffective disorder

Board pearl: Cannabis use in adolescence roughly doubles lifetime psychosis risk and can precipitate FEP in genetically vulnerable patients — always quantify potency, frequency, and age of first use

Physical Exam Findings (and Neurologic/Vital Sign Assessment)

— Fever → infectious encephalitis, NMS, serotonin syndrome, thyroid storm

— Tachycardia, hypertension, mydriasis, diaphoresis → stimulant intoxication, anticholinergic toxicity, alcohol/benzo withdrawal

— Bradycardia, miosis → opioid (usually sedation, not psychosis, but co-ingestion)

— Hypothermia, bradycardia → myxedema, severe malnutrition

— Level of consciousness: clear sensorium argues for primary psychiatric; fluctuating attention = delirium

— Orientation, attention (serial 7s, months backward), short-term recall

— Thought form, thought content, perceptual disturbances, insight, judgment

— Affect: flat, constricted, inappropriate, labile

— Cranial nerves, pupils, EOM

— Focal motor/sensory deficits → stroke, mass, MS

— Cerebellar signs, gait

— Movement abnormalities: baseline tics, chorea (Huntington, SLE, autoimmune), parkinsonism, catatonia (waxy flexibility, posturing, mutism, echopraxia, stupor)

— Frontal release signs in older patients → neurodegeneration

General appearance and vitals — the screening filter for "medical mimic":

Mental status exam (MSE):

Neurologic exam — must be documented in FEP:

Skin and general: track marks, rashes (lupus malar, neurocutaneous stigmata — tuberous sclerosis), Kayser-Fleischer rings (Wilson disease in young patient with psychosis + movement disorder + LFT changes), thyroid enlargement

Catatonia screen with Bush-Francis: ≥2 features triggers a lorazepam challenge (1–2 mg IV/IM); response confirms diagnosis and guides treatment

CCS pearl: On a CCS case of new psychosis, your first orders are vitals, fingerstick glucose, pulse oximetry, full neuro exam, and urine toxicology — before ordering an antipsychotic. Missing delirium and giving haloperidol to an anticholinergic-toxic patient or NMS-prone patient is a classic distractor

Board pearl: Young adult with psychosis + orofacial dyskinesias + autonomic instability + seizures → anti-NMDA receptor encephalitis — get LP and autoantibody panel

Diagnostic Workup — Initial Labs, Imaging, ECG

— CBC with differential

— CMP (electrolytes, glucose, BUN/Cr, LFTs, calcium)

— TSH (free T4 if abnormal)

— Urinalysis

— Urine drug screen (cannabinoids, amphetamines, cocaine, PCP, opioids, benzodiazepines) — note synthetic cannabinoids and bath salts are missed

— Urine pregnancy test in any patient who can become pregnant

— Blood alcohol level

— HIV and RPR/syphilis serology — neurosyphilis and HIV can present as psychosis

— Hepatitis B/C if risk factors

— Fasting glucose or HbA1c

— Fasting lipid panel

— Weight, height, BMI, waist circumference, blood pressure

— Prolactin (especially before risperidone/paliperidone)

— Baseline QTc before starting antipsychotics — many prolong QT (ziprasidone, IV haloperidol most; olanzapine, risperidone moderate; aripiprazole, lurasidone minimal)

— Recheck after dose titration if QTc borderline or on interacting drugs

— Non-contrast head CT in the ED if focal neuro signs, head trauma, age >40 at onset, rapid progression, or atypical features

— Brain MRI is preferred for non-emergent evaluation of FEP — higher yield for tumors, demyelination, mesial temporal sclerosis, vascular lesions

— Routine MRI in every FEP case is not universally mandated but is recommended by most academic guidelines given the once-in-a-lifetime opportunity to find a reversible cause

Rationale: FEP requires a medical clearance workup to exclude secondary causes and to establish a baseline before starting antipsychotics (which affect glucose, lipids, QTc, prolactin, weight)

Initial labs (every FEP patient):

Metabolic baseline (also pre-antipsychotic):

ECG:

Imaging:

Step 3 management: Order labs, ECG, and consider MRI before committing to a primary psychiatric diagnosis. Document a negative medical workup — this is exam-tested and medicolegally protective

Board pearl: Don't forget B12, folate, ceruloplasmin (Wilson if <40 yo + neuro/hepatic signs), ANA — selectively, based on history

Diagnostic Workup — Advanced or Confirmatory Studies

— Fever, meningismus, altered consciousness

— Rapid onset (days to weeks), seizures, focal deficits

— Movement disorder + psychosis (anti-NMDA receptor encephalitis)

— Immunocompromise (HIV, transplant)

— Send: cell count, glucose, protein, Gram stain/culture, HSV PCR, VDRL, autoimmune encephalitis panel (NMDAR, LGI1, CASPR2, GABA-B, AMPA)

— Suspected seizure (especially temporal lobe / complex partial mimicking psychosis), nonconvulsive status, anti-NMDA encephalitis ("extreme delta brush")

— Consider in catatonia and unexplained altered mental status

— Anti-NMDA receptor antibodies (serum and CSF; CSF more sensitive)

— Paraneoplastic panel if rapid cognitive decline, age >50, smoking history, or known malignancy

— Pelvic US/MRI in women with anti-NMDA encephalitis → ovarian teratoma (resection is curative)

— Ceruloplasmin, 24-hr urine copper, slit-lamp for Wilson disease

— Heavy metals (lead, mercury, arsenic) in occupational/environmental exposure

— Porphyrins if abdominal pain + neuropsychiatric symptoms

— Genetic testing (e.g., 22q11.2 deletion / velocardiofacial syndrome — ~25% develop psychosis; look for cardiac anomalies, cleft palate, hypocalcemia)

— Huntington testing if family history + chorea

Lumbar puncture — indications in FEP:

EEG:

Autoimmune/paraneoplastic workup:

Targeted testing based on clues:

Neuropsychological testing: later, to characterize cognitive deficits and guide rehab — not part of acute workup

Substance-specific confirmation: synthetic cannabinoid panel, bath salts panel, GC-MS confirmation if clinical picture doesn't match standard UDS

Key distinction: Primary psychotic disorder = normal labs, normal imaging, normal sensorium, gradual onset, family history, age <40, prodrome. Secondary psychosis = abnormal vitals, fluctuating mental status, focal findings, abrupt onset, atypical age, or atypical hallucination modality

Board pearl: A young woman with subacute psychiatric symptoms, orofacial dyskinesias, autonomic instability, and seizures → CSF anti-NMDA antibodies + pelvic imaging for teratoma; treat with IVIG/steroids/plasmapheresis and tumor resection — not just antipsychotics

Risk Stratification and First-Line Management Logic

— Assess suicide risk (FEP carries ~5% lifetime suicide risk; highest in first 1–2 years)

— Homicidal ideation, command hallucinations, weapons access

— Ability to maintain food, fluid, shelter, medical care

— Substance intoxication/withdrawal severity

— Voluntary inpatient psychiatry: patient agrees, needs stabilization

— Involuntary hold (e.g., 5150 in CA, varies by state): danger to self/others or grave disability and refuses care

— Partial hospitalization / intensive outpatient if mild, stable, supportive family, no safety concerns

— Outpatient Coordinated Specialty Care (CSC) referral — strongest evidence for FEP outcomes

— Substance-induced → support through withdrawal, monitor for resolution (typically <1 month); persistent psychosis beyond intoxication window reclassifies as primary disorder

— Medical/neurologic cause → treat it (e.g., teratoma resection, antiviral for HSV encephalitis, levothyroxine for myxedema, steroids/IVIG for autoimmune encephalitis)

— Start low-dose second-generation antipsychotic (SGA) — FEP patients are more responsive and more sensitive to side effects than chronic patients

— Use measurement-based care (PANSS, BPRS, or clinician global impression)

— Allow 2–4 weeks at therapeutic dose before declaring nonresponse; full response can take 6 weeks

— Family psychoeducation, CBT for psychosis (CBTp), supported employment/education, case management, peer support, substance use treatment

— RAISE trial: CSC superior to usual care for symptoms, quality of life, school/work engagement — most benefit when DUP <74 weeks

Step 1 — Safety and disposition:

Disposition decision:

Step 2 — Treat underlying cause when identified:

Step 3 — Initiate antipsychotic for primary psychotic disorder or persistent symptoms:

Step 4 — Wrap psychosocial scaffolding around medication:

Step 3 management: The right answer for stable, cooperative FEP is outpatient referral to a Coordinated Specialty Care program + low-dose SGA + family involvement — not high-dose monotherapy or polypharmacy

Board pearl: Shorter DUP = better outcome. Aggressive early identification and linkage to CSC is the single most impactful intervention

Pharmacotherapy — First-Line Drug Regimen

— Aripiprazole 5–10 mg/day → up to 15–20 mg; D2 partial agonist; lowest metabolic burden, minimal prolactin elevation; can cause akathisia

— Risperidone 1–2 mg/day → 2–4 mg; effective but highest prolactin elevation, dose-dependent EPS above 6 mg

— Olanzapine 5–10 mg/day → 10–20 mg; highly effective but worst metabolic profile (weight, glucose, lipids); reserve if others fail or for severe agitation

— Lurasidone 40 mg/day with food (≥350 kcal) → 40–80 mg; low metabolic risk

— Ziprasidone 40 mg BID with food → up to 80 mg BID; QTc prolongation

— Haloperidol and other high-potency first-generation agents as first-line (more EPS, more tardive dyskinesia, more discontinuation)

— Clozapine is NOT first-line — reserved for treatment-resistant schizophrenia (failure of ≥2 adequate antipsychotic trials)

— Consider early in FEP for adherence — recent evidence supports first-episode LAI use to reduce relapse

— Options: aripiprazole monthly, paliperidone monthly/3-monthly/6-monthly, risperidone biweekly

— Lorazepam 1–2 mg for agitation, anxiety, insomnia, or catatonia

— Benztropine or diphenhydramine for acute dystonia; propranolol for akathisia; amantadine or benztropine for parkinsonism

— Avoid benzodiazepines long-term (dependence, cognitive blunting)

— Weight/BMI at baseline, 4, 8, 12 weeks, then quarterly

— Fasting glucose and lipids at baseline, 12 weeks, then annually

— Blood pressure and waist circumference quarterly

— Prolactin if symptomatic (galactorrhea, sexual dysfunction, amenorrhea)

— AIMS exam for tardive dyskinesia every 6 months (every 3 months if on FGA)

Drug class: Second-generation (atypical) antipsychotics are first-line for FEP — equivalent efficacy to first-generation, fewer EPS, but more metabolic risk

Preferred agents in FEP (start low, go slow):

Avoid in FEP:

Long-acting injectables (LAIs):

Adjuncts:

Monitoring schedule (ADA/APA consensus):

Board pearl: In FEP, aripiprazole or risperidone at the lowest effective dose is the typical right answer — balancing efficacy, EPS, metabolic effects, and adherence. Olanzapine wins on raw efficacy but loses on metabolic harm in young patients

Expanded Pharmacology — Treatment Resistance, Catatonia, Agitation

— Definition: failure of ≥2 adequate trials (6 weeks each at therapeutic dose) of different antipsychotics

— Clozapine is the only FDA-approved agent for TRS and for suicidality in schizophrenia

— Dosing: start 12.5 mg, titrate slowly to 300–450 mg/day; therapeutic level 350–600 ng/mL

— Mandatory monitoring (REMS): ANC weekly × 6 months, biweekly × 6 months, then monthly indefinitely. Hold for ANC <1500 (or <1000 in benign ethnic neutropenia)

— Adverse effects: agranulocytosis, myocarditis (first 4–8 weeks — check troponin/CRP if symptoms), seizures (dose-dependent, >600 mg), metabolic syndrome, sialorrhea, ileus/severe constipation, orthostasis

— First-line: lorazepam 1–2 mg IV/IM, repeat q4–6h, titrate up to 8–24 mg/day

— Second-line: ECT — highly effective, especially in malignant catatonia (autonomic instability, fever, rigidity)

— Avoid antipsychotics in catatonia until benzodiazepines tried — antipsychotics can precipitate NMS in catatonic patients

— Verbal de-escalation first; offer oral medication

— Oral: olanzapine ODT 10 mg, risperidone 2 mg, or aripiprazole 10–15 mg ± lorazepam 1–2 mg

— IM (if needed): olanzapine 10 mg IM OR haloperidol 5 mg + lorazepam 2 mg + benztropine 1 mg ("B-52")

— Avoid IM olanzapine + IM benzodiazepine together (respiratory depression, hypotension)

— Avoid IV haloperidol unless on telemetry (QTc, torsades)

— Smoking induces CYP1A2 → lowers olanzapine and clozapine levels; cessation can cause toxicity

— Fluvoxamine and ciprofloxacin inhibit CYP1A2 → raise clozapine levels dangerously

Treatment-resistant schizophrenia (TRS):

Catatonia:

Acute agitation in FEP (ED setting):

Drug interactions:

CCS pearl: In a CCS case of agitated psychosis, order vitals, fingerstick, UDS, ECG, then olanzapine 10 mg IM or haloperidol + lorazepam + benztropine IM for severe agitation; reassess in 30–60 min; avoid restraints if chemical sedation suffices

Board pearl: Two failed antipsychotic trials = move to clozapine, not a third standard agent

Special Populations — Elderly and Renal/Hepatic Impairment

— Much higher likelihood of secondary cause — dementia (especially Lewy body, frontotemporal, Alzheimer with psychosis), delirium, stroke, brain tumor, medication-induced (anticholinergics, dopaminergics, steroids), metabolic

— Mandatory: MRI brain, cognitive testing (MoCA), thorough medication review, delirium workup

— Black box warning: antipsychotics increase mortality (stroke, sudden death) in elderly with dementia-related psychosis

— Non-pharmacologic strategies first (environmental, behavioral)

— If antipsychotic necessary: lowest dose, shortest duration; document risk/benefit discussion with family

— Pimavanserin is FDA-approved specifically for Parkinson disease psychosis (no dopamine blockade — doesn't worsen motor symptoms)

— Avoid typical antipsychotics and risperidone/olanzapine — severe sensitivity reactions, worsened parkinsonism

— Preferred: quetiapine (low dose) or pimavanserin; clozapine if refractory

— Paliperidone is renally excreted — dose-adjust or avoid in CrCl <50

— Risperidone: reduce dose in CrCl <30

— Lithium (if mood-spectrum): renally cleared, avoid in CKD or use very cautiously

— Most antipsychotics are hepatically metabolized — start lower, titrate slower

— Avoid chlorpromazine (cholestasis), monitor LFTs on olanzapine, quetiapine

— Clozapine: avoid in active hepatitis

— Start at ¼ to ½ usual adult dose

— Greater orthostasis, falls, anticholinergic delirium, EPS, QTc effects

— Avoid anticholinergic prophylaxis (benztropine) in elderly — use amantadine instead

Late-onset psychosis (>40 yo) and very-late-onset (>60 yo):

Dementia-related psychosis:

Lewy body dementia / Parkinson disease:

Renal impairment:

Hepatic impairment:

Dose adjustments in elderly:

Step 3 management: In an elderly patient with new psychosis, the right first answer is rule out delirium and review the medication list before reaching for an antipsychotic. Stopping the offending drug often resolves symptoms

Board pearl: Visual hallucinations + parkinsonism + fluctuating cognition + REM sleep behavior disorder → Lewy body dementia — avoid haloperidol, risperidone, olanzapine; use quetiapine or pimavanserin

Special Populations — Pregnancy, Pediatrics, and Demographic Subgroups

— Untreated psychosis carries significant risk — self-neglect, poor prenatal care, substance use, suicide, infanticide

— Do not stop antipsychotics reflexively in pregnancy

— Preferred agents: haloperidol, olanzapine, quetiapine, risperidone have the most reproductive safety data; aripiprazole increasingly used

— Avoid: paroxetine (if comorbid depression), valproate (NTDs, neurodevelopmental — contraindicated in mood-spectrum psychosis in pregnancy), carbamazepine (NTDs)

— Third-trimester antipsychotic exposure → neonatal adaptation syndrome (EPS, feeding difficulty, transient withdrawal); notify pediatrics

— Breastfeeding: olanzapine and quetiapine have low infant exposure; clozapine contraindicated (agranulocytosis risk in infant)

— Psychiatric emergency — onset typically within 2 weeks postpartum

— High infanticide and suicide risk

— Treat: inpatient hospitalization, antipsychotic, mood stabilizer (lithium if not breastfeeding or with monitoring), often ECT for rapid response

— Strong association with bipolar disorder — screen carefully

— Rare before puberty; when present, work up aggressively for medical causes

— FDA-approved pediatric SGAs: aripiprazole, risperidone, olanzapine, quetiapine, paliperidone

— Greater sensitivity to weight gain, metabolic effects, prolactin elevation, sedation

— Address school accommodations (IEP/504 plan), family education

— Distinguish culturally sanctioned beliefs (religious experiences, folk illness) from psychosis — not delusional if shared within cultural group and not impairing

— Use trained interpreters; avoid family-as-interpreter for psychiatric content

Pregnancy:

Postpartum psychosis:

Pediatric/adolescent FEP:

Cultural considerations:

22q11.2 deletion syndrome: ~25% lifetime psychosis risk — screen if cardiac anomalies, cleft palate, hypocalcemia, characteristic facies

Board pearl: Acute psychosis within days to weeks of delivery → postpartum psychosis, hospitalize, treat aggressively (often with lithium + antipsychotic ± ECT); never send home with the infant unsupervised

Key distinction: Postpartum blues (transient, ≤2 weeks, no psychosis) vs postpartum depression (persistent mood) vs postpartum psychosis (emergency)

Complications and Adverse Outcomes

— Suicide: ~5–10% lifetime; highest in early course, after discharge, with depressive symptoms, high premorbid functioning, insight into illness

— Violence: small absolute risk increase, concentrated in untreated psychosis with substance use, command hallucinations, persecutory delusions

— Functional decline: school dropout, unemployment, homelessness, social isolation

— Substance use comorbidity (>50%): cannabis, tobacco, alcohol

— Premature mortality: 15–20 year reduced life expectancy, mostly cardiovascular

— Medical comorbidity: obesity, T2DM, dyslipidemia, HTN — both illness-related and antipsychotic-related

— Extrapyramidal symptoms (EPS):

— Acute dystonia (hours-days): IM benztropine 1–2 mg or diphenhydramine 50 mg

— Akathisia (days-weeks): propranolol, benztropine, lower dose, switch agent; misdiagnosed as agitation

— Parkinsonism (weeks): reduce dose, switch, add amantadine

— Tardive dyskinesia (months-years): often irreversible; VMAT2 inhibitors (valbenazine, deutetrabenazine) are FDA-approved

— Neuroleptic malignant syndrome (NMS): fever, rigidity ("lead pipe"), autonomic instability, altered mental status, elevated CK, leukocytosis → stop antipsychotic, supportive care, dantrolene or bromocriptine, ICU

— Metabolic syndrome: weight gain (olanzapine, clozapine > quetiapine > risperidone > aripiprazole, ziprasidone, lurasidone), dyslipidemia, T2DM

— QTc prolongation, torsades

— Hyperprolactinemia: galactorrhea, gynecomastia, amenorrhea, sexual dysfunction, long-term bone loss — risperidone, paliperidone, haloperidol worst

— Anticholinergic: dry mouth, constipation, urinary retention, delirium

— Clozapine-specific: agranulocytosis, myocarditis, seizures, ileus, sialorrhea

Disease-related complications:

Medication adverse effects:

Key distinction: NMS (rigidity, hyperthermia, slow onset days, lead-pipe, elevated CK) vs serotonin syndrome (clonus, hyperreflexia, agitation, faster onset hours, recent serotonergic drug) vs malignant catatonia (catatonic features precede autonomic instability — often indistinguishable, treat with benzodiazepines/ECT)

Board pearl: New rigidity + fever + altered mental status on antipsychotic = stop the drug, check CK, ICU-level supportive care — don't escalate the antipsychotic

When to Escalate Care — ICU, Consult, or Inpatient Triage

— Active suicidal or homicidal ideation with plan/intent

— Command hallucinations directing harm

— Inability to maintain self-care (food, fluid, shelter, medical needs) = grave disability

— Severe agitation unmanageable in ED

— Need for medication initiation/stabilization with monitoring

— Failed outpatient stabilization

— Lack of safe disposition / no supportive environment

— Requires danger to self, danger to others, or grave disability AND refusal of voluntary care

— Process and duration vary by state (typically 72 hours initial hold, extendable with court review)

— Document specific behaviors, statements, and clinical reasoning

— NMS, malignant catatonia, severe autonomic instability

— Severe overdose, mixed drug toxicity

— Hemodynamic instability from any cause

— Status epilepticus (anti-NMDA encephalitis)

— Need for ECT in medically complex patient

— Neurology: focal signs, seizures, movement disorder, suspected encephalitis or dementia

— Internal medicine: medical workup, comorbid disease management

— Endocrinology: thyroid storm, adrenal disease

— OB/Gyn: pregnancy, postpartum psychosis, suspected teratoma

— Social work: housing, benefits, family support, CSC linkage

— Stable, cooperative, supportive family, no safety concern → outpatient CSC referral + start SGA, follow-up in 1 week

— Moderate symptoms, partial insight, mild safety concern → partial hospital or intensive outpatient

— Active danger, grave disability, treatment refusal → inpatient (voluntary if possible, involuntary if needed)

— Medical instability or NMS → medical ICU first, psychiatry consult

— Highest suicide risk in 30 days post-discharge — ensure follow-up within 7 days, ideally with warm handoff to CSC team

— Medication reconciliation, family education, crisis plan in writing

Inpatient psychiatric admission criteria:

Involuntary commitment:

Medical ICU transfer:

Consultations:

Step 3 management — CCS triage:

Transition-of-care risk:

CCS pearl: Don't keep an NMS patient on the psychiatric floor — transfer to ICU, stop the antipsychotic, supportive care, then re-introduce a different agent later at low dose once stable

Key Differentials — Same-Category (Psychiatric) Causes

— ≥2 of (delusions, hallucinations, disorganized speech, disorganized/catatonic behavior, negative symptoms) for ≥1 month, with continuous signs for ≥6 months, functional decline

— At least one symptom must be delusions, hallucinations, or disorganized speech

— Major mood episode (depression or mania) concurrent with active-phase schizophrenia symptoms

— ≥2 weeks of psychosis WITHOUT prominent mood symptoms at some point in the illness (this distinguishes it from psychotic mood disorder)

— Mood symptoms present for majority of total illness duration

— Psychosis only during mood episodes (mania or severe depression)

— Mood-congruent grandiose or persecutory delusions typical in mania

— Treat with mood stabilizer (lithium, valproate) + antipsychotic

— Mood-congruent guilt, nihilistic, somatic delusions

— Treat with antidepressant + antipsychotic, or ECT (often more effective than meds)

— Non-bizarre delusion(s) ≥1 month, functioning otherwise relatively preserved, no other psychotic features

— Subtypes: erotomanic, grandiose, jealous, persecutory, somatic, mixed

— Odd beliefs, magical thinking, perceptual distortions, social anxiety — subthreshold for psychosis

— Cluster A; can precede schizophrenia

Schizophrenia:

Schizophreniform disorder: same criteria as schizophrenia but 1–6 months total duration

Brief psychotic disorder: ≥1 day to <1 month, full return to premorbid function; often after stressor or postpartum

Schizoaffective disorder:

Bipolar I disorder with psychotic features:

Major depressive disorder with psychotic features:

Delusional disorder:

Schizotypal personality disorder:

Shared psychotic disorder (folie à deux): rare, removed from DSM-5 as separate entity; delusion shared with closely associated person — separation often resolves in the secondary individual

Post-traumatic intrusions / dissociative phenomena: can mimic psychosis but tied to trauma, ego-dystonic, intact reality testing about the experience

Key distinction: Duration is the linchpin among primary psychotic disorders — <1 month (brief), 1–6 months (schizophreniform), ≥6 months (schizophrenia). Mood overlay tips toward schizoaffective or psychotic mood disorder

Board pearl: "Mood-incongruent delusions during mania" still = bipolar with psychotic features, as long as psychosis is confined to mood episodes

Key Differentials — Other-Category (Medical/Neurologic/Substance) Causes

— Cannabis (especially high-THC, synthetic cannabinoids): paranoia, hallucinations

— Stimulants (cocaine, methamphetamine, MDMA): paranoia, persecutory delusions, tactile hallucinations (formication)

— Hallucinogens (LSD, psilocybin, PCP, ketamine): perceptual distortions, dissociation; PCP causes violent agitation, nystagmus

— Alcohol withdrawal: delirium tremens (autonomic, tremor, hallucinations) or alcoholic hallucinosis (auditory, clear sensorium)

— Benzodiazepine withdrawal: similar to alcohol

— Corticosteroids: dose-dependent psychosis, mania, depression

— Anticholinergics, levodopa, dopamine agonists, interferon, isoniazid, antimalarials

— Anti-NMDA receptor encephalitis — young woman, psychiatric prodrome, orofacial dyskinesia, seizures, autonomic instability; ovarian teratoma

— Temporal lobe epilepsy — postictal or interictal psychosis

— Multiple sclerosis — rarely psychosis as presenting feature

— Stroke (especially right hemisphere, frontal, thalamic)

— Brain tumor (frontal, temporal)

— Traumatic brain injury, CTE

— Neurodegenerative: Lewy body dementia (visual hallucinations), frontotemporal dementia, Huntington, Wilson, Alzheimer

— HSV encephalitis, neurosyphilis, HIV-associated, PML, prion disease

— Thyroid storm, myxedema madness

— Cushing syndrome, Addison crisis

— Hypoglycemia, hyperglycemia (HHS)

— Hyponatremia, hypercalcemia

— B12 deficiency, folate deficiency

— Hepatic encephalopathy, uremia

— Acute intermittent porphyria

— Fluctuating attention and consciousness, acute onset, often reversible

— Always consider in elderly, hospitalized, or medically ill patients with "new psychosis"

Substance-induced psychotic disorder:

Neurologic causes:

Endocrine/metabolic:

Autoimmune/inflammatory: SLE (lupus cerebritis), neurosarcoidosis, paraneoplastic

Delirium — the great mimicker:

Key distinction: Delirium has clouded sensorium and fluctuating course; primary psychosis has clear sensorium and stable consciousness. This single feature reorients the entire workup

Board pearl: Visual hallucinations as the dominant feature + clear sensorium → think Charles Bonnet (visual loss), Lewy body, occipital lesion, hallucinogen, or alcohol withdrawal — not schizophrenia

Secondary Prevention, Discharge Medications, and Long-Term Plan

— Continue antipsychotic for at least 1–2 years after first episode even with full remission (APA guideline)

— Relapse risk on discontinuation: ~80% within 1 year vs ~20% with maintenance

— After relapse: indefinite maintenance is reasonable

— Lowest effective dose; do not under-dose into relapse, do not over-dose into side effects

— Strongly consider early — adherence problems are universal in FEP

— Aripiprazole monthly, paliperidone monthly/3-month/6-month, risperidone biweekly, olanzapine monthly (post-injection delirium/sedation — REMS-monitored)

— Smoking cessation (60–80% prevalence in schizophrenia): varenicline (safe in stable psychiatric patients per EAGLES trial), NRT, bupropion

— Substance use treatment — integrated dual-diagnosis care

— Weight management: nutrition counseling, exercise, metformin for antipsychotic-induced weight gain (evidence-supported)

— Sleep hygiene, exercise prescription

— Weight/BMI: baseline, 4, 8, 12 wk, then quarterly

— Fasting glucose/A1c, lipids: baseline, 12 wk, annually

— BP: each visit

— Treat dyslipidemia (statin), HTN, diabetes per general guidelines — don't undertreat in psychiatric patients

— CBT for psychosis (CBTp)

— Family psychoeducation (reduces relapse by ~50%)

— Supported employment/education (Individual Placement and Support model)

— Social skills training

— Peer support and case management

— Antipsychotic at lowest effective dose

— Metabolic monitoring plan

— CSC referral with appointment within 7 days

— Crisis plan and emergency contacts

— Family education session

— Smoking cessation and substance use referrals as needed

— Primary care linkage

Continuation pharmacotherapy:

Long-acting injectables (LAIs):

Address modifiable risk factors:

Cardiometabolic monitoring (ADA/APA):

Vaccinations and preventive care: influenza, COVID, pneumococcal, hepatitis B; cancer screening — patients with serious mental illness are undervaccinated and underscreened

Psychosocial interventions (continue indefinitely):

Step 3 management — discharge bundle for FEP:

Board pearl: Adherence is the dominant driver of relapse — LAI + CSC in FEP outperforms oral monotherapy + treatment-as-usual on every meaningful outcome

Follow-Up, Monitoring Parameters, and Rehab/Counseling

— Within 7 days of discharge — highest relapse and suicide risk window

— Weekly for first month

— Biweekly to monthly for first 6 months

— Quarterly once stable, with CSC team continuity for 2–3 years

— Symptoms: positive (PANSS or brief rating), negative, cognitive, mood

— Suicide and violence risk

— Adherence (pill count, LAI date, patient and family report)

— Side effects: EPS (AIMS for tardive dyskinesia every 6 months), akathisia, sedation, sexual dysfunction, weight

— Substance use

— Function: school, work, social, self-care

— Metabolic panel: baseline, 12 wk, annually (more often if abnormal or on olanzapine/clozapine)

— Lipids: baseline, 12 wk, annually

— Prolactin: if symptomatic

— ECG: if QTc-prolonging regimen or new symptoms (syncope, palpitations)

— Clozapine: weekly CBC × 6 mo, then biweekly × 6 mo, then monthly

— Individual Placement and Support (IPS): rapid job placement with ongoing support — superior to prevocational training

— Supported education for students

— CBTp: targets distressing delusions and hallucinations, improves coping

— Family psychoeducation: reduces expressed emotion (criticism, hostility, overinvolvement → relapse trigger)

— Social skills training, illness self-management, WRAP (Wellness Recovery Action Plan)

— Psychoeducation about diagnosis, prognosis, medication

— Stress vulnerability model

— Early warning signs of relapse (sleep change, social withdrawal, suspiciousness)

— Substance use risks, especially cannabis

— Driving safety while sedated or symptomatic

— ~20% achieve sustained recovery after single episode

— ~50% achieve significant improvement with recurring episodes

— Best predictors: short DUP, female sex, good premorbid function, acute onset, absence of substance use, family support, treatment adherence

Follow-up cadence:

What to monitor at each visit:

Laboratory monitoring:

Rehabilitation components:

Patient and family counseling:

Outcome expectations:

Step 3 management: The 7-day post-discharge appointment is not optional — schedule it before discharge, with warm handoff

Board pearl: High expressed emotion in family is one of the strongest modifiable relapse predictors — family psychoeducation directly addresses it

Ethical, Legal, and Patient Safety Considerations

— Psychosis does not automatically equal incapacity — assess for the specific decision

— Capacity requires: understand information, appreciate situation, reason about options, communicate choice

— Document capacity assessment; involve surrogate decision-maker if patient lacks capacity for a specific treatment

— A patient can refuse a medication while still meeting hospitalization criteria; involuntary medication typically requires separate court order or specific statutory authority (varies by state)

— Standard: danger to self, danger to others, or grave disability + mental illness + refusal of voluntary care

— Use least restrictive alternative — outpatient civil commitment / Assisted Outpatient Treatment (AOT) where available

— Document specific behaviors, statements, and clinical reasoning — not just diagnosis

— Identifiable potential victim + credible threat → duty to take protective action (warn victim, notify police, hospitalize)

— Specifics vary by state; know your jurisdiction

— Child or elder abuse/neglect, including self-neglect in some states

— Some states require reporting of patients who threaten violence

— Counsel about driving while symptomatic or sedated; some states require physician reporting of impaired drivers

— Lethal means counseling: remove firearms during high-risk periods (newly diagnosed, post-discharge, suicidal); document the discussion

— HIPAA permits disclosure to prevent serious imminent harm

— Family involvement is therapeutic but requires patient consent for specific information sharing; you can listen to family without disclosing

— Highest suicide risk in first 30 days post-discharge — schedule follow-up within 7 days, ensure prescription filled, provide crisis line, warm handoff to CSC

— Medication reconciliation errors at every transition — verify each med

— Patients with SMI receive lower-quality medical care — actively address screening, cardiometabolic care, pain

— Avoid diagnostic overshadowing (attributing new medical symptoms to psychiatric illness)

Informed consent and decision-making capacity:

Involuntary commitment:

Duty to warn / Tarsoff:

Mandatory reporting:

Driving and firearm safety:

Confidentiality:

Transition-of-care risk (Step 3 favorite):

Stigma and equity:

Research and capacity: for research consent in psychotic patients, use independent capacity assessment and surrogate consent processes

Board pearl: A FEP patient who refuses medication but agrees to hospitalization can be admitted voluntarily — you cannot force medication without specific legal authority. Document the conversation, offer alternatives, and engage family with consent

High-Yield Associations and Rapid-Fire Clinical Facts

— Brief psychotic disorder: 1 day – <1 month

— Schizophreniform: 1–6 months

— Schizophrenia: ≥6 months

— Schizoaffective: ≥2 weeks of psychosis without mood symptoms

Duration cutoffs:

Cannabis in adolescence → ~2× lifetime psychosis risk; dose- and potency-dependent

Anti-NMDA receptor encephalitis: young woman, psychiatric prodrome, dyskinesias, seizures, autonomic instability → CSF antibodies, pelvic imaging for teratoma

Lewy body dementia: visual hallucinations + parkinsonism + fluctuating cognition + REM sleep behavior disorder → avoid haloperidol/risperidone/olanzapine; use quetiapine or pimavanserin

Postpartum psychosis within 2 weeks of delivery → emergency, often bipolar spectrum, treat with antipsychotic + mood stabilizer ± ECT

22q11.2 deletion → ~25% lifetime psychosis; look for cardiac anomalies, cleft palate, hypocalcemia

Wilson disease in young patient with psychosis + tremor/dystonia + LFT abnormality → ceruloplasmin, slit lamp, urine copper

Clozapine is the only agent FDA-approved for treatment-resistant schizophrenia and for suicidality in schizophrenia

Clozapine red flags: fever in first month → rule out myocarditis (troponin, CRP, echo); ANC drop → REMS protocol; severe constipation → ileus

NMS: fever, lead-pipe rigidity, AMS, autonomic instability, elevated CK → stop antipsychotic, supportive care, dantrolene/bromocriptine

Tardive dyskinesia treatment: valbenazine or deutetrabenazine (VMAT2 inhibitors)

Akathisia treatment: propranolol or benztropine; reduce/switch antipsychotic

Acute dystonia: IM benztropine or diphenhydramine

Highest metabolic burden: clozapine ≈ olanzapine >> quetiapine > risperidone > aripiprazole, lurasidone, ziprasidone

Highest prolactin elevation: risperidone, paliperidone, haloperidol

Lowest QTc effect: aripiprazole, lurasidone

Pimavanserin: Parkinson disease psychosis (5HT2A inverse agonist, no D2 blockade)

Post-discharge follow-up: within 7 days; highest suicide risk in first 30 days

CSC/RAISE trial: coordinated specialty care superior to usual care, especially with DUP <74 weeks

Smoking cessation: varenicline safe per EAGLES trial in stable psychiatric patients

Step 3 management: First episode = low-dose SGA + CSC + family psychoeducation + metabolic monitoring + 7-day follow-up — every time

Board Question Stem Patterns

Stem 1 — Classic schizophrenia onset: 19-year-old college student with 8 months of declining grades, social withdrawal, and recent belief that classmates are inserting thoughts into his head; clear sensorium, normal vitals. → Diagnosis: schizophrenia (if ≥6 mo) or schizophreniform; next step: rule out substances, start low-dose SGA, refer to CSC

Stem 2 — Substance-induced: 22-year-old at music festival, paranoid, tachycardic, mydriatic, formication. → Methamphetamine/cocaine intoxication; supportive care, benzodiazepines for agitation, observe for resolution

Stem 3 — Anti-NMDA encephalitis: 24-year-old woman, 3 weeks of psychiatric symptoms, now with orofacial dyskinesias, seizures, autonomic instability. → CSF anti-NMDAR antibodies + pelvic imaging for teratoma; IVIG/steroids, tumor resection

Stem 4 — Postpartum psychosis: Day 10 postpartum, woman with delusions about baby being possessed. → Emergency hospitalization, separate from infant supervision-wise, antipsychotic + lithium (or ECT); high bipolar association

Stem 5 — Lewy body dementia: 74-year-old with progressive cognitive decline, well-formed visual hallucinations, parkinsonism, REM sleep behavior disorder. → Avoid haloperidol/risperidone; use quetiapine or pimavanserin

Stem 6 — NMS: Patient 5 days on haloperidol now with 39.5°C, rigidity, CK 8000, confusion. → Stop haloperidol, ICU supportive care, dantrolene/bromocriptine

Stem 7 — Treatment resistance: 28-year-old with schizophrenia, failed adequate trials of risperidone and aripiprazole. → Start clozapine with REMS monitoring

Stem 8 — Catatonia: Patient mute, posturing, waxy flexibility. → Lorazepam 1–2 mg IV challenge; ECT if refractory; avoid antipsychotics first-line

Stem 9 — Akathisia mistaken for agitation: Recently started risperidone, inner restlessness, can't sit still. → Diagnose akathisia, propranolol; don't increase antipsychotic

Stem 10 — Tardive dyskinesia: Years on haloperidol, now lip-smacking, tongue movements. → VMAT2 inhibitor (valbenazine or deutetrabenazine)

Stem 11 — Capacity vs commitment: Patient with psychosis refusing medication, no danger, accepts hospitalization. → Admit voluntarily; cannot force medication without separate legal process

Stem 12 — Post-discharge follow-up: Just discharged after FEP admission. → Schedule appointment within 7 days, warm handoff to CSC, lethal means counseling, family education

Board pearl: When the stem mentions visual or olfactory hallucinations, abnormal vitals, age >40 onset, or movement disorder, the answer is almost never "start an antipsychotic" — it's "work up the medical cause first"

One-Line Recap

First-episode psychosis is a medical-and-psychiatric emergency requiring rigorous exclusion of substance, medical, and neurologic causes followed by early initiation of a low-dose second-generation antipsychotic embedded within a Coordinated Specialty Care program — because the duration of untreated psychosis is the single most modifiable determinant of long-term outcome.

— Workup before label: every FEP gets vitals, neuro exam, CBC/CMP/TSH/UDS/HIV/RPR/pregnancy/ECG, baseline metabolic panel, and MRI consideration; add LP/EEG/autoimmune panel when the clinical picture demands (young woman with dyskinesias, fever, seizures, fluctuating sensorium)

— Drug of choice: low-dose aripiprazole or risperidone first-line; olanzapine if severe but watch metabolic burden; clozapine only after two failed adequate trials; LAIs early to address adherence

— Wrap-around care wins: Coordinated Specialty Care (RAISE model) — low-dose meds + CBTp + family psychoeducation + supported employment/education + case management — outperforms medication alone, especially when DUP is short

— Don't miss the mimics: anti-NMDA encephalitis (young woman + dyskinesias + teratoma), Lewy body dementia (visual hallucinations + parkinsonism → avoid typical antipsychotics), postpartum psychosis (emergency, bipolar spectrum), substance-induced (cannabis, stimulants), neurosyphilis/HIV, Wilson, 22q11.2, thyroid storm/myxedema

— Safety scaffolding: assess suicide/violence, document capacity, use least restrictive setting, Tarasoff and lethal means counseling where applicable, schedule 7-day post-discharge follow-up because the first 30 days carry the highest suicide risk

— Long game: continue antipsychotic at least 1–2 years after first episode; monitor weight, glucose, lipids, prolactin, AIMS; treat smoking, substance use, and cardiometabolic disease aggressively to close the 15–20 year mortality gap

High-yield recap bullets:

Step 3 management: Right answer for stable FEP is almost always low-dose SGA + CSC referral + family involvement + metabolic monitoring + 7-day follow-up — anything else is a distractor