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Psychiatry
Primary Care

Schizophrenia

High EvidenceUpdated: 2025-12-22

On This Page

Red Flags

  • Suicide risk (10% lifetime)
  • Violence risk (rare but assess)
  • Catatonia
  • First episode psychosis
  • Non-adherence with treatment
Overview

Schizophrenia

1. Topic Overview

Summary

Schizophrenia is a chronic, severe mental disorder characterised by disturbances in thought, perception, behaviour, and affect. It typically presents with positive symptoms (hallucinations, delusions, disorganised thinking) and negative symptoms (flat affect, avolition, social withdrawal). Cognitive impairment is common and often precedes the first psychotic episode. Treatment is lifelong, centring on antipsychotic medication (oral or depot) combined with psychological therapies (CBT for psychosis, family interventions). Clozapine is reserved for treatment-resistant schizophrenia. Early intervention in psychosis significantly improves outcomes.

Key Facts

  • Definition: Chronic psychotic disorder with ≥2 characteristic symptoms for ≥6 months
  • Prevalence: ~1% lifetime risk
  • Onset: Late adolescence to early adulthood (males ~18-25; females slightly later)
  • Positive Symptoms: Hallucinations (auditory), delusions, disorganised thought/speech
  • Negative Symptoms: Flat affect, avolition, alogia, anhedonia
  • First-Line Treatment: Oral antipsychotic + psychological therapy
  • Treatment-Resistant: Clozapine (after 2 adequate antipsychotic trials fail)

Clinical Pearls

"Treat Early, Treat Effectively": Duration of untreated psychosis (DUP) predicts outcomes. Shorter DUP = better prognosis.

"Clozapine Saves Lives": Treatment-resistant schizophrenia (30%) requires clozapine — the most effective antipsychotic. Don't delay referral.

"Metabolic Monitoring is Essential": Antipsychotics cause weight gain, diabetes, dyslipidaemia. Monitor and manage cardiovascular risk.

Why This Matters Clinically

Schizophrenia is a leading cause of disability worldwide. Untreated or poorly treated schizophrenia leads to relapse, hospitalisation, social isolation, and premature death (20-year reduced life expectancy, mainly from cardiovascular disease and suicide).


2. Epidemiology

Prevalence

MeasureValue
Lifetime Risk~1%
Point Prevalence0.3-0.7%
Incidence15 per 100,000/year

Demographics

FactorDetails
Age of OnsetMales 18-25; Females 25-35
SexEqual prevalence; males earlier onset, worse outcomes
EthnicityHigher incidence in migrants, urban dwellers

Risk Factors

FactorDetails
Genetic80% heritability; 10% if first-degree relative
Obstetric ComplicationsHypoxia, infection, stress
Cannabis Use2-6x increased risk (especially adolescent, high-THC)
Urban Living2x risk vs rural
Migration2-3x risk

3. Pathophysiology

Dopamine Hypothesis

  • Mesolimbic Hyperactivity → Positive symptoms
  • Mesocortical Hypoactivity → Negative and cognitive symptoms
  • Antipsychotics block D2 receptors (reduce positive symptoms)

Glutamate Hypothesis

  • NMDA receptor hypofunction
  • Explains negative and cognitive symptoms

Neurodevelopmental Model

  • Abnormal brain development (prenatal/perinatal insults)
  • Synaptic pruning abnormalities in adolescence
  • Structural changes: Enlarged ventricles, reduced grey matter

4. Clinical Presentation

Positive Symptoms

SymptomDetails
Auditory Hallucinations3rd person, running commentary, command
DelusionsPersecutory, reference, control, grandiose
Disorganised ThoughtTangentiality, derailment, thought blocking
Disorganised BehaviourUnpredictable, inappropriate

Negative Symptoms

SymptomDetails
Flat AffectReduced emotional expression
AvolitionLack of motivation
AlogiaPoverty of speech
AnhedoniaInability to experience pleasure
AsocialitySocial withdrawal

Red Flags

[!CAUTION] Red Flags:

  • Suicide risk (10% lifetime)
  • Violence risk (rare; assess command hallucinations)
  • Catatonia
  • First episode psychosis
  • Non-adherence

5. Clinical Examination

Mental State Examination

DomainFindings
AppearancePoor hygiene, neglect
BehaviourAgitation, stereotypies, catatonia
SpeechPoverty, pressure, neologisms
MoodIncongruent affect, flat
Thought FormLoose associations, derailment
Thought ContentDelusions, ideas of reference
PerceptionAuditory hallucinations
CognitionImpaired attention, working memory
InsightOften poor

6. Investigations
TestPurpose
FBC, U&E, LFTsBaseline, organ function
TFTsExclude thyroid cause
HbA1c, LipidsMetabolic baseline
Urine Drug ScreenExclude substance-induced psychosis
CT/MRI BrainFirst episode to exclude organic cause
ECGBaseline before antipsychotic (QTc)

7. Management

Pharmacotherapy

First-Line: Oral antipsychotic (aripiprazole, risperidone, olanzapine)

Depot (LAI): If adherence concerns

Treatment-Resistant: Clozapine (after 2 failed trials)

Psychological Therapies

  • CBT for psychosis (CBTp)
  • Family intervention
  • Art therapies
  • Vocational support (IPS)

Physical Health

  • Metabolic monitoring
  • Smoking cessation
  • Cardiovascular risk management

8. Complications
ComplicationNotes
RelapseCommon with non-adherence; depot reduces risk
Suicide10% lifetime risk
Substance Misuse50% comorbidity
Metabolic SyndromeWeight gain, diabetes, CVD
Reduced Life Expectancy15-20 years shorter (CVD, suicide)
Social IsolationUnemployment, relationship breakdown

9. Prognosis & Outcomes

Course

PatternNotes
Rule of Thirds1/3 recover, 1/3 partial recovery, 1/3 chronic
First Episode80% remit; 80% relapse within 5 years if untreated

Prognostic Factors

GoodPoor
Acute onsetInsidious onset
Later age of onsetYoung male
Good premorbid functioningPre-existing cognitive impairment
Predominant positive symptomsPredominant negative symptoms
Good treatment adherenceCannabis use
Short DUPLong duration of untreated psychosis

10. Evidence & Guidelines

Key Guidelines

  1. NICE CG178: Psychosis and schizophrenia in adults (2014)

Landmark Trials

CATIE (2005) — Antipsychotic comparison

  • Key finding: Olanzapine most effective but highest metabolic burden
  • Clinical Impact: Side effect profile guides choice

CUtLASS (2006) — FGA vs SGA

  • Key finding: No clear superiority of SGAs over well-chosen FGAs

11. Patient/Layperson Explanation

What is Schizophrenia?

Schizophrenia is a long-term mental health condition that affects how you think, feel, and behave. It can cause symptoms like hearing voices that others don't hear, believing things that aren't true, or feeling emotionally flat.

What are the symptoms?

  • Hearing voices (hallucinations)
  • False beliefs (delusions)
  • Confused thinking
  • Lack of motivation
  • Difficulty with emotions and social connections

How is it treated?

  1. Medication: Antipsychotic tablets or injections help control symptoms
  2. Talking therapies: CBT helps you cope with symptoms
  3. Support: Family therapy, employment support, social skills training

What to expect

  • Most people improve with treatment
  • Medication is usually needed long-term
  • With support, many people live fulfilling lives

12. References

Primary Guidelines

  1. National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management (CG178). 2014. nice.org.uk/guidance/cg178

Key Trials

  1. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia (CATIE). N Engl J Med. 2005;353(12):1209-1223. PMID: 16172203

Further Resources

  • Rethink Mental Illness: rethink.org
  • Mind: mind.org.uk


Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. If you are experiencing psychosis or mental health crisis, please seek help immediately.

Last updated: 2025-12-22

At a Glance

EvidenceHigh
Last Updated2025-12-22

Red Flags

  • Suicide risk (10% lifetime)
  • Violence risk (rare but assess)
  • Catatonia
  • First episode psychosis
  • Non-adherence with treatment

Clinical Pearls

  • **"Treat Early, Treat Effectively"**: Duration of untreated psychosis (DUP) predicts outcomes. Shorter DUP = better prognosis.
  • **"Clozapine Saves Lives"**: Treatment-resistant schizophrenia (30%) requires clozapine — the most effective antipsychotic. Don't delay referral.
  • **"Metabolic Monitoring is Essential"**: Antipsychotics cause weight gain, diabetes, dyslipidaemia. Monitor and manage cardiovascular risk.
  • - Suicide risk (10% lifetime)
  • - Violence risk (rare; assess command hallucinations)

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines