Up to 20% of apparent first-episode psychosis has an underlying organic cause. Autoimmune encephalitis (anti-NMDA receptor), CNS infection, metabolic derangement, and substance-induced psychosis must be excluded before psychiatric diagnosis. Missing encephalitis carries mortality risk. Command hallucinations represent immediate danger and require urgent psychiatric assessment — never manage alone in primary care.

Accurate symptom characterisation determines urgency and referral pathway. Brief psychotic disorder (duration <1 month) often follows acute stress and may resolve — but still needs urgent CMHT input. Negative symptoms are frequently missed and are the best predictor of functional outcome. Collateral history is often the most reliable information when insight is impaired.

Treatment diverges significantly by diagnosis. Bipolar disorder requires mood stabilisers, not antipsychotics alone. Organic psychosis requires treatment of the underlying cause. Early Intervention in Psychosis (EIP) services achieve significantly better outcomes when accessed within the first episode — delay worsens prognosis. NICE NG185 mandates EIP access for all first-episode psychosis regardless of age.

People with severe mental illness receive fewer physical health assessments and have 15–20 years reduced life expectancy — partly from physical comorbidities. Physical examination at first presentation establishes a baseline and excludes treatable organic causes. Neurological examination is especially important; viral encephalitis and CNS tumours can present with psychiatric symptoms.

NICE NG185 recommends metabolic, thyroid, and infection screening at first presentation. HIV testing is recommended given the high prevalence of psychiatric manifestations. Baseline ECG is essential before antipsychotic initiation — QT prolongation increases arrhythmia risk (torsades de pointes). Urine drug screen informs differential and management even if positive, as substance use and primary psychosis co-exist in ~50% of cases.

Duration of untreated psychosis (DUP) is the strongest modifiable predictor of outcome — each week of delay worsens prognosis. EIP services reduce relapse rates, improve employment, and reduce hospitalisation. NICE NG185 (2020) mandates EIP referral for all ages with first-episode psychosis. GPs should not wait for certainty of diagnosis — EIP teams assess and confirm.

Antipsychotics are effective in 70–80% of first-episode psychosis when used adequately. Starting at low doses reduces extrapyramidal side effects (EPS). Olanzapine and clozapine cause significant metabolic syndrome — weight gain, diabetes, dyslipidaemia — requiring metabolic monitoring. Aripiprazole has the most favourable metabolic profile (NICE preferred). Clozapine is the only evidence-based treatment for treatment-resistant schizophrenia but requires mandatory neutrophil monitoring due to agranulocytosis risk (1–2%).

NICE NG185 places CBTp and family intervention alongside antipsychotics as first-line treatment. Family intervention is the single most effective intervention for reducing relapse in those with high expressed emotion households. Cannabis use is the most important modifiable environmental risk factor — high-potency cannabis users have 5x risk of psychosis compared to non-users. Physical health must be actively managed; people with schizophrenia die 15–20 years earlier, primarily from cardiovascular disease.

Patients on antipsychotics have high rates of metabolic syndrome (up to 40%). Annual physical health reviews by GPs reduce the mortality gap. Neuroleptic malignant syndrome (NMS) is rare but life-threatening — hyperthermia, rigidity, altered consciousness — requires immediate cessation and emergency admission. Relapse signatures allow early intervention, reducing the need for hospitalisation. GP–CMHT communication is essential; GPs often see patients more frequently and are well-placed to detect early deterioration.