Quick Overview
Schizophrenia is a severe mental illness affecting ~1% of the population, characterized by positive symptoms (hallucinations, delusions), negative symptoms (apathy, social withdrawal), and cognitive impairment. NICE CG178 emphasizes early intervention in first-episode psychosis (FEP), systematic antipsychotic selection, and structured pathways for treatment-resistant schizophrenia (TRS). Timely recognition and evidence-based management significantly improve long-term outcomes.
Core Facts & Concepts
Diagnostic Criteria (ICD-10)
- ≥1 month of symptoms with ≥1 of: thought echo/insertion/withdrawal/broadcasting, delusions of control, persistent delusions, persistent hallucinations (typically auditory)
- Or ≥2 of: persistent hallucinations, thought disorder, catatonic behavior, negative symptoms
First-Episode Psychosis (FEP) Pathway
- 🎯 NICE target: Assessment by Early Intervention in Psychosis (EIP) service within 2 weeks of referral
- EIP services for ≥3 years or until age 65 (whichever longer)
- Start antipsychotic at lowest licensed dose, titrate cautiously
Antipsychotic Choice Algorithm
- Discuss benefits/risks of oral antipsychotics (first-generation vs second-generation)
- Consider: metabolic (weight gain, diabetes), extrapyramidal (akathisia, parkinsonism), cardiovascular (QTc), prolactin effects
- Avoid polypharmacy: Use monotherapy unless during cross-titration
- Review response at 4-6 weeks; if inadequate, trial different antipsychotic (offer ≥2 agents)
Clozapine Initiation Criteria
- 💊 TRS definition: Inadequate response to ≥2 antipsychotics (including ≥1 second-generation) each trialed for 6-8 weeks at therapeutic dose
- Clozapine = gold standard for TRS (~30% of cases)
- Requires weekly FBC for 18 weeks, then fortnightly to 52 weeks, then monthly (monitor neutropenia risk)
Monitoring Requirements
| Parameter | Baseline | Week 12 | Annually |
|---|---|---|---|
| Weight/BMI | ✓ | ✓ | ✓ |
| Lipids/glucose | ✓ | ✓ | ✓ |
| BP/pulse | ✓ | ✓ | ✓ |
| Prolactin | If symptomatic | - | If symptomatic |
| ECG | If risk factors | - | If on high-dose |
Problem-Solving Approach
Managing Treatment Resistance
- Confirm diagnosis: Rule out substance misuse, organic causes, medication non-adherence
- Optimize current antipsychotic: Ensure adequate dose/duration (6-8 weeks therapeutic trial)
- Trial second antipsychotic: Different class if first trial failed
- Consider clozapine after 2 failed trials (don't delay-efficacy time-sensitive)
- Augmentation strategies if partial clozapine response: Add aripiprazole, amisulpride, or ECT
Acute Agitation/Violence
- 🚩 De-escalation first: Verbal, environmental modification
- Rapid tranquilization: IM lorazepam (1-2mg) OR IM haloperidol (5mg) + promethazine (50mg)
- Monitor every 15 minutes post-IM (respiratory rate, BP, temperature, hydration)
- Avoid combining IM antipsychotic + benzodiazepine unless essential
⚠️ Warning: Antipsychotic polypharmacy increases mortality risk-avoid except during cross-titration
Red Flags Requiring Urgent Action
- 🚩 Neuroleptic malignant syndrome: Fever, rigidity, elevated CK, autonomic instability
- 🚩 Clozapine neutropenia: Neutrophils <1.5×10⁹/L (stop immediately)
- 🚩 QTc >500ms or >60ms increase from baseline
- 🚩 Acute dystonia/oculogyric crisis (give IM procyclidine 5-10mg)
Analysis Framework
Differential Diagnosis of Psychosis
| Condition | Key Discriminators | Duration |
|---|---|---|
| Schizophrenia | Negative symptoms, functional decline | >1 month |
| Brief psychotic disorder | Acute stressor, full recovery | <1 month |
| Schizoaffective | Mood episodes concurrent with psychosis | Variable |
| Drug-induced | Temporal link to substance (cannabis, stimulants) | Resolves with abstinence |
| Delirium | Fluctuating consciousness, acute onset | Days-weeks |
| Bipolar (manic) | Elevated mood, grandiosity predominate | ≥1 week |
First-Generation vs Second-Generation Antipsychotics
| Feature | First-Gen (e.g., haloperidol) | Second-Gen (e.g., olanzapine) |
|---|---|---|
| Extrapyramidal effects | Higher risk | Lower risk |
| Metabolic effects | Lower risk | Higher risk (weight, diabetes) |
| Prolactin elevation | More common | Variable (risperidone high) |
| Cost | Lower | Higher |
Visual Aid
Clozapine Monitoring Schedule
| Timeframe | FBC Frequency | Action if Neutrophils <1.5 |
|---|---|---|
| Weeks 1-18 | Weekly | Stop clozapine, daily FBC |
| Weeks 19-52 | Fortnightly | Stop, refer hematology |
| After 52 weeks | Monthly | Stop, urgent specialist review |
Key Points Summary
✓ FEP pathway: EIP assessment within 2 weeks, start antipsychotic at lowest dose, provide ≥3 years specialized care
✓ TRS criteria: Inadequate response to ≥2 antipsychotics (including ≥1 second-generation) each for 6-8 weeks at therapeutic dose-then offer clozapine
✓ Clozapine monitoring: Weekly FBC for 18 weeks, fortnightly to 52 weeks, monthly thereafter; stop if neutrophils <1.5×10⁹/L
✓ Avoid polypharmacy: Use antipsychotic monotherapy; combining agents increases mortality without clear benefit
✓ Monitoring essentials: Weight/glucose/lipids at baseline, 12 weeks, and annually; ECG if cardiovascular risk factors or high-dose therapy
✓ Rapid tranquilization: De-escalate first; if needed, use IM lorazepam OR haloperidol + promethazine; monitor every 15 minutes post-administration
✓ Common pitfall: Declaring treatment resistance before ensuring adequate dose/duration and ruling out non-adherence or substance misuse
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