Psychotic disorders are defined by abnormalities in one or more of five domains: delusions, hallucinations, disorganized thinking (speech), grossly disorganized or abnormal motor behavior (including catatonia), and negative symptoms. Schizophrenia usually begins in late adolescence or early adulthood, often after a prodromal phase of social withdrawal, declining school or work performance, and odd beliefs.

Causes and mechanisms

• Strong genetic contribution plus environmental risks: obstetric complications, childhood adversity, migration, urban upbringing, and heavy cannabis use in adolescence
• Dopamine hypothesis: excess dopamine activity in the mesolimbic pathway → positive symptoms; reduced activity in the mesocortical pathway → negative and cognitive symptoms
• Glutamate (NMDA receptor) hypofunction and muscarinic (acetylcholine) pathways also contribute — the basis for newer non-dopamine-blocking treatment
• Structural changes: enlarged ventricles, reduced gray matter

Symptom groups

Negative and cognitive symptoms predict long-term disability more than positive symptoms and respond less to medication.

DSM-5-TR spectrum — duration is the key discriminator

The old subtypes (paranoid, catatonic, disorganized, undifferentiated, residual) were removed in DSM-5; catatonia is now recorded as a specifier.

Delusions (fixed false beliefs not shared by the culture)

Hallucinations — auditory most common; command hallucinations telling the client to harm self or others are a safety emergency. Visual, tactile, or olfactory hallucinations should prompt a search for medical or substance causes.

Disorganized thinking and speech — loose associations, tangentiality, word salad, neologisms, clang associations, echolalia, concrete thinking, thought blocking.

Other findings — inappropriate or flat affect, poor hygiene, social withdrawal, lack of insight (anosognosia), suicidal ideation (lifetime suicide risk is high), substance use, smoking, and excessive water drinking (psychogenic polydipsia with hyponatremia) in some clients.

No laboratory test confirms schizophrenia; testing excludes other causes and establishes medication baselines.

Antipsychotic classes

Class warnings for dopamine-blocking (first- and second-generation) antipsychotics, including clozapine: boxed warning — increased mortality in older adults with dementia-related psychosis; neuroleptic malignant syndrome, tardive dyskinesia, orthostatic hypotension and falls, lowered seizure threshold, leukopenia, and heat intolerance. Third-trimester exposure can cause neonatal EPS or withdrawal; untreated psychosis also harms pregnancy, so decisions are individualized.

Clozapine — the most effective drug for treatment-resistant illness, with serious risks

• Severe neutropenia/agranulocytosis (boxed warning): baseline ANC must be ≥ 1,500/µL (≥ 1,000/µL in benign ethnic neutropenia). Monitor ANC weekly for 6 months, every 2 weeks for months 6–12, then monthly. Teach to report fever, sore throat, flu-like symptoms, or any infection immediately
• ANC action thresholds (general population, current labeling): 1,000–1,499/µL (mild) → continue, check ANC three times weekly; 500–999/µL (moderate) → interrupt clozapine, notify prescriber, hematology consultation, resume only when ANC ≥ 1,000/µL; below 500/µL (severe) → discontinue, hematology consultation. In benign ethnic neutropenia, 500–999/µL → continue with three-times-weekly ANC; below 500/µL → discontinue
• The FDA eliminated the clozapine REMS in 2025: pharmacies no longer need ANC reporting before dispensing, but ANC monitoring per the prescribing information is still recommended
• Other boxed or major warnings: orthostatic hypotension, bradycardia, syncope (slow titration; restart low if ≥ 2 days missed); seizures (dose-related); myocarditis and cardiomyopathy (mostly first 2 months — chest pain, tachycardia, fever, dyspnea); severe constipation and ileus (bowel regimen, report no bowel movement or abdominal pain)
• Also sialorrhea (drooling), weight gain, diabetes, fever early in treatment
• Smoking induces clozapine metabolism — stopping smoking (e.g., on a smoke-free unit) can raise levels and cause toxicity

Xanomeline-trospium

• Starts 50 mg/20 mg twice daily and is titrated; taken at least 1 hour before or 2 hours after a meal
• Contraindicated in urinary retention, moderate or severe hepatic impairment, gastric retention, untreated narrow-angle glaucoma, or hypersensitivity. Not recommended in mild hepatic impairment, moderate–severe renal impairment, or active biliary disease (e.g., symptomatic gallstones)
• Check liver enzymes, bilirubin, and heart rate before starting. Adverse effects: nausea, dyspepsia, vomiting, constipation, hypertension, tachycardia, dizziness; risks of urinary retention (older men with BPH), decreased GI motility, angioedema, and angle-closure glaucoma
• Low risk of EPS, weight gain, and prolactin elevation

Psychosocial treatment — coordinated specialty care for first-episode psychosis, CBT for psychosis, family psychoeducation, social skills training (conversation, self-care, problem-solving, work skills), supported employment, and assertive community treatment. Catatonia: first-line lorazepam (IV, IM, or oral); ECT if there is no response. ECT is also used in some treatment-resistant cases.

Monitoring schedule: weight monthly for 3 months, then quarterly; BP, fasting glucose or HbA1c, and lipids at baseline, 12 weeks, then annually; AIMS at baseline and at least every 6 months (every 12 months for lower-risk clients).

Listed in priority order.

1. Safety of client and others
   • Assess suicide risk and command hallucinations directly ("What are the voices telling you to do?")
   • Early de-escalation: calm voice, space, choices; seclusion or restraint only as a last resort under policy and orders
   • Remove hazards; observe closely during acute agitation
2. Medication emergencies and adverse effects

1. Hallucinations
   • Do not argue or pretend to hear the voices: "I don't hear the voices, but I understand they are real and frightening to you"
   • Focus on the feeling and the present reality; offer distraction (music, walking, humming, talking with staff)
2. Delusions
   • Neither argue with nor agree with the delusion; respond to the underlying feeling (fear, anxiety) and redirect to reality-based topics
   • Build trust with consistent, brief contacts; avoid whispering or laughing near a suspicious client; avoid unnecessary touch
3. Disorganized communication — short, simple, concrete statements; clarify; one instruction at a time
4. Negative symptoms and self-care
   • Plan small, achievable activities based on the client's interests; praise effort; structured daily routine
   • Assist with hygiene, nutrition, and sleep while encouraging maximum independence
5. Physical health — weight, BP, glucose, and lipids per metabolic monitoring schedule; smoking cessation support; bowel habits on clozapine; fluid intake and weight in clients with polydipsia

• Take medication every day even when feeling well; relapse is most often linked to stopping medication. Ask about long-acting injections if daily pills are hard
• Do not stop antipsychotics abruptly; report restlessness, stiffness, muscle spasms, or unusual movements of the mouth or tongue
• Report fever with muscle stiffness or confusion immediately (NMS)
• Rise slowly to prevent dizziness; avoid overheating and dehydration; use sunscreen (especially with chlorpromazine)
• Healthy diet and exercise to limit weight gain; routine weight, glucose, and cholesterol checks
• Clozapine: keep every blood test appointment; report fever, sore throat, chest pain, or constipation lasting more than a couple of days; tell the team before starting or stopping smoking
• Avoid alcohol and cannabis — they worsen psychosis and interact with medications
• Families: learn early warning signs of relapse (sleep change, withdrawal, suspiciousness); a calm, low-criticism home environment reduces relapse

• Positive = added (hallucinations, delusions, disorganization); negative = lost (flat affect, alogia, avolition, anhedonia, asociality)
• Schizophrenia = ≥ 2 symptoms for 1 month (one must be delusions, hallucinations, or disorganized speech) + ≥ 6 months total
• Brief psychotic 1 day–1 month; schizophreniform 1–6 months; delusional disorder ≥ 1 month
• Schizoaffective = mood episode concurrent with psychosis plus ≥ 2 weeks of psychosis without mood symptoms
• Delusions: do not argue, do not agree — respond to the feeling
• Command hallucinations → assess content and safety first
• Clozapine → ANC monitoring (weekly for 6 months); report fever or sore throat; also seizures, myocarditis, ileus
• EPS order: dystonia (hours–days) → akathisia and parkinsonism (weeks) → tardive dyskinesia (months–years)
• Acute dystonia is an emergency → IM benztropine or diphenhydramine
• NMS = fever, rigidity, confusion, autonomic instability, high CK → stop the drug
• Xanomeline-trospium: no direct D2 blockade; contraindicated in urinary retention, gastric retention, untreated narrow-angle glaucoma, moderate–severe hepatic impairment