Schizophrenia

Schizophrenia is a chronic psychotic disorder with positive symptoms, negative symptoms, disorganisation and cognitive impairment, persisting for at least 6 months.

• Lifetime prevalence about 0.7%, onset late teens to early 20s in men and later in women.
• Heritability 80%; risk factors: obstetric complications, urban birth, migration, cannabis use, childhood trauma.
• Dopamine hyperactivity in mesolimbic pathways and NMDA receptor hypofunction.
• Life expectancy is shortened by 15 to 20 years (cardiovascular, metabolic, suicide in 5 to 10%).

• Hallucinations (auditory), delusions (persecutory), disorganised speech and behaviour, catatonia.
• Negative: blunted affect, avolition, alogia, social withdrawal.
• Cognitive deficits in memory, attention and executive function; poor insight.
• Premorbid social decline, prodrome, comorbid substance misuse, depression.

• DSM-5 criteria; clinical interview, collateral history, PANSS or BPRS for severity.
• Exclude organic and substance causes: urine toxicology, TSH, full blood count, electrolytes, calcium, HIV, syphilis, B12, liver and renal tests, MRI brain, EEG if seizures, autoimmune encephalitis antibodies (acute atypical presentations), Wilson disease in the young.
• Baseline weight, waist, blood pressure, fasting glucose or HbA1c, lipids, prolactin, ECG.
• Suicide and violence risk assessment.

• Early intervention services, shared decision making, family intervention, cognitive behavioural therapy for psychosis, supported employment.
• First episode: monotherapy at low dose: risperidone 2 to 4 mg daily, olanzapine 10 to 20 mg, aripiprazole 10 to 30 mg, amisulpride 400 to 800 mg, quetiapine 400 to 800 mg; assess after 2 to 6 weeks, continue 1 to 2 years minimum after first episode and indefinitely for relapses.
• Adherence problems: long acting injectables (paliperidone palmitate 150 mg day 1, 100 mg day 8, then 75 to 150 mg monthly; aripiprazole 400 mg monthly; risperidone LAI 25 to 50 mg every 2 weeks; olanzapine pamoate; flupentixol decanoate).
• Treatment resistance (failure of two antipsychotics at adequate dose for 6 weeks): clozapine, start 12.5 mg and titrate to 300 to 450 mg daily, with absolute neutrophil monitoring weekly for 18 weeks then monthly, ECG, troponin, constipation prevention; clozapine reduces suicide risk.
• Side effects: extrapyramidal (procyclidine), hyperprolactinaemia, weight gain (metformin 500 to 2000 mg), QT prolongation, tardive dyskinesia (valbenazine, deutetrabenazine).
• Acute agitation: lorazepam 1 to 2 mg, olanzapine 5 to 10 mg IM, haloperidol 5 mg IM with ECG.
• Manage substance misuse, cardiovascular risk, smoking cessation; negative symptoms: cariprazine 1.5 to 6 mg, psychosocial therapy.