Schizophrenia
Summary
Schizophrenia is a chronic, severe mental disorder characterised by disturbances in thought, perception, emotion, and behaviour. It affects approximately 1% of the population worldwide and typically presents in late adolescence or early adulthood. The illness is defined by positive symptoms (hallucinations, delusions), negative symptoms (apathy, social withdrawal, poverty of speech), and cognitive impairment. Treatment involves long-term antipsychotic medication, psychological therapy, and psychosocial support. Early intervention improves outcomes.
Key Facts
- Prevalence: 1% lifetime risk worldwide
- Peak Onset: Males 18-25, Females 25-35
- Genetics: 10x risk if first-degree relative affected
- Mortality: 15-20 years reduced life expectancy
- Treatment Response: 70-80% respond to first-line antipsychotics
- Treatment Resistance: 30% require clozapine
- Prognosis: Rule of thirds (1/3 recover, 1/3 variable, 1/3 chronic)
Clinical Pearls
High-Yield Points:
- Schneider's First Rank Symptoms are suggestive but NOT diagnostic
- Negative symptoms predict functional outcome more than positive symptoms
- Clozapine is the only antipsychotic effective for treatment-resistance
- Always monitor metabolic parameters on antipsychotics
- Substance misuse is common and worsens course
- Early intervention (first 3-5 years) is critical for long-term outcomes
Why This Matters Clinically
Schizophrenia is among the most disabling mental disorders and a major cause of years lived with disability. Early recognition and treatment during the first episode can significantly alter the disease course. Understanding the pharmacology and side effects of antipsychotics is essential, as metabolic syndrome, diabetes, and cardiovascular disease contribute to the reduced life expectancy.
Prevalence and Incidence
| Metric | Value |
|---|---|
| Lifetime Prevalence | 0.7-1% |
| Annual Incidence | 15 per 100,000 |
| Male:Female | 1.4:1 |
| Peak Onset (Male) | 18-25 years |
| Peak Onset (Female) | 25-35 years |
Risk Factors
Genetic:
- First-degree relative affected: 10x risk
- Monozygotic twin: 50% concordance
- Dizygotic twin: 15% concordance
Environmental:
- Urban birth/upbringing (2x risk)
- Migration (2-5x risk, especially with discrimination)
- Cannabis use (especially adolescent high-potency)
- Childhood trauma
- Obstetric complications (hypoxia)
- Winter/spring birth (slight increase)
Prodrome
- Social withdrawal
- Declining function (school, work)
- Unusual ideas/behaviour
- Sleep disturbance
- Suspiciousness
- Duration: Months to years before first episode
Dopamine Hypothesis
Core Theory:
- Positive Symptoms: Excess dopamine in mesolimbic pathway
- Negative/Cognitive Symptoms: Decreased dopamine in mesocortical pathway
Evidence:
- Antipsychotics (D2 blockers) reduce positive symptoms
- Dopamine agonists (amphetamines) can induce psychosis
- PET studies show increased striatal dopamine synthesis
Glutamate Hypothesis
- NMDA receptor hypofunction
- Explains cognitive symptoms and negative symptoms better
- Ketamine/PCP (NMDA antagonists) produce schizophrenia-like states
- Basis for potential future glutamatergic therapies
Neurodevelopmental Model
- Genetic susceptibility + Environmental insults (prenatal)
- Abnormal brain development (reduced synaptic pruning)
- Structural changes (enlarged ventricles, reduced grey matter)
- Stress/cannabis triggers psychosis in vulnerable individuals
Positive Symptoms
Hallucinations:
Delusions:
Thought Disorder:
Passivity Phenomena:
Negative Symptoms (The 5 A's)
| Symptom | Description |
|---|---|
| Affective Flattening | Reduced emotional expression |
| Alogia | Poverty of speech |
| Anhedonia | Inability to experience pleasure |
| Avolition | Lack of motivation |
| Asociality | Social withdrawal |
Cognitive Symptoms
Schneider's First Rank Symptoms
- Auditory hallucinations (third person, running commentary, thought echo)
- Thought insertion, withdrawal, broadcast
- Passivity experiences (made feelings, impulses, actions)
- Delusional perception
Note: First-rank symptoms are suggestive but not pathognomonic
Mental State Examination
| Domain | Typical Findings |
|---|---|
| Appearance | May be unkempt, unusual dress |
| Behaviour | Guarded, responding to unseen stimuli |
| Speech | Poverty, tangentiality, neologisms |
| Mood | Often incongruent or flat |
| Affect | Blunted, inappropriate |
| Thought Form | Loosening of associations, derailment |
| Thought Content | Delusions, ideas of reference |
| Perception | Hallucinations (auditory > visual) |
| Cognition | May be impaired (frontal/executive) |
| Insight | Often impaired |
Risk Assessment
- Suicide risk: 5-10% lifetime suicide rate
- Violence risk: Slightly elevated, mostly due to comorbid substance use
- Vulnerability: Risk of exploitation, homelessness
Purpose: Rule Out Organic Causes
| Investigation | Rationale |
|---|---|
| FBC, U&Es, LFTs, TFTs | Organic causes, baseline |
| Glucose, Lipids, HbA1c | Metabolic baseline (pre-antipsychotic) |
| Urine Drug Screen | Cannabis, amphetamines, cocaine |
| CT/MRI Brain | First episode: Exclude organic lesion |
| ECG | Pre-antipsychotic (QTc) |
Baseline Monitoring (Before Starting Antipsychotics)
- Weight, BMI, waist circumference
- Blood pressure, pulse
- Fasting glucose/HbA1c
- Lipid profile
- ECG (especially if using haloperidol, ziprasidone)
Subtypes
| Subtype | Features |
|---|---|
| Paranoid | Prominent delusions/hallucinations, less negative symptoms |
| Hebephrenic | Disorganised behaviour, flat/inappropriate affect, early onset |
| Catatonic | Motor abnormalities (stupor, posturing, waxy flexibility) |
| Undifferentiated | Mixed features |
| Residual | Prominent negative symptoms after acute phase |
| Simple | Insidious negative symptoms without prominent positive symptoms |
Course Specifiers
- First episode, currently in acute episode
- First episode, currently in partial/full remission
- Multiple episodes
- Continuous
Acute Phase
First Episode Psychosis:
- Urgent assessment (Early Intervention in Psychosis team)
- Physical health screen
- Initiate antipsychotic after investigation
Choice of Antipsychotic (First-Line):
| Drug | Starting Dose | Target | Notes |
|---|---|---|---|
| Risperidone | 2 mg OD | 4-6 mg | Good efficacy, EPSE dose-related |
| Olanzapine | 10 mg OD | 10-20 mg | Effective, significant weight gain |
| Aripiprazole | 10-15 mg OD | 15-30 mg | Metabolically favourable, activating |
| Quetiapine | 50 mg BD | 300-750 mg | Sedating, useful for sleep |
Principles:
- Low dose, slow titration
- Trial for 4-6 weeks at therapeutic dose
- If no response → switch antipsychotic
- If 2 trials fail → clozapine
Clozapine (Treatment-Resistant Schizophrenia)
Indication: Failure of 2 adequate antipsychotic trials
Efficacy: 30-60% respond to clozapine when other antipsychotics fail
Monitoring (MANDATORY):
- Weekly FBC for 18 weeks
- Then fortnightly for 1 year
- Then monthly
Side Effects:
- Agranulocytosis (1-2%) - STOP if neutrophils <1.5
- Hypersalivation, constipation (can be severe → ileus)
- Myocarditis (first 2 months)
- Metabolic syndrome
Maintenance Phase
- Continue antipsychotic for at least 1 year after first episode
- 2+ years if high relapse risk
- Lifelong if multiple relapses
Depot (Long-Acting Injectables):
- Consider for non-adherence
- Options: Paliperidone, Aripiprazole, Risperidone depots
Psychological Therapy
| Therapy | Evidence |
|---|---|
| CBT for Psychosis (CBTp) | NICE recommended; reduces distress from symptoms |
| Family Intervention | Reduces relapse rates |
| Art Therapies | Engagement, expression |
Psychosocial Support
- Early Intervention in Psychosis (EIP) teams
- Supported employment (IPS model)
- Supported housing
- Education and vocational support
Acute
| Complication | Management |
|---|---|
| Acute dystonia | Procyclidine IM/IV |
| Akathisia | Reduce dose, beta-blocker |
| NMS | Stop antipsychotic, supportive care, dantrolene |
| Catatonia | Benzodiazepines, ECT |
Chronic
- Metabolic syndrome (20-40%)
- Tardive dyskinesia (irreversible movement disorder)
- Cardiovascular disease (leading cause of death)
- Suicide (5-10% lifetime)
- Social isolation, unemployment
- Substance misuse (50% lifetime)
Rule of Thirds
| Outcome | Proportion |
|---|---|
| Good recovery | ~25% |
| Moderate course | ~50% |
| Chronic severe | ~25% |
Prognostic Factors
Good Prognosis:
- Late onset
- Female
- Acute onset (vs insidious)
- Prominent positive symptoms
- Good premorbid function
- Supportive family
- High income country
- Treatment adherence
Poor Prognosis:
- Early onset (adolescence)
- Male
- Prominent negative symptoms
- Long duration of untreated psychosis (DUP)
- Substance misuse
- Poor insight
Key Guidelines
| Guideline | Organisation | Year |
|---|---|---|
| Psychosis and Schizophrenia | NICE CG178 | 2014 (Updated 2024) |
| EIP Standards | NHS England | 2016 |
| PORT Guidelines | APA | 2019 |
Key Evidence
- CATIE: Effectiveness of antipsychotics comparable; high discontinuation rates
- CUtLASS: Second-generation not clearly superior to first-generation
- OPUS: Early intervention improves outcomes
What is Schizophrenia?
Schizophrenia is a mental health condition that affects how a person thinks, feels, and perceives the world. It can cause symptoms like hearing voices that others don't hear, believing things that aren't true, and difficulty with everyday activities. It's a medical condition, not a character flaw.
What causes it?
- Genetics: It runs in families, but most people with schizophrenia don't have a family history
- Brain chemistry: Imbalances in dopamine and other chemicals
- Environment: Stress, trauma, or drug use can trigger it in vulnerable people
How is it treated?
- Medication: Antipsychotics help control symptoms for most people
- Talking therapies: Help manage symptoms and improve daily life
- Support: Help with work, housing, and social activities
With proper treatment, many people with schizophrenia lead fulfilling lives.
When to seek urgent help
Go to A&E or call 999 if:
- You or someone else is at risk of harm
- Someone is very confused or not caring for themselves
- There are command hallucinations to harm
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NICE. Psychosis and schizophrenia in adults: prevention and management (CG178). 2014 (Updated 2024). nice.org.uk
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Howes OD, et al. The Dopamine Hypothesis of Schizophrenia: Version III. Schizophr Bull. 2009;35(3):549-562. PMID: 19325164
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Kane J, et al. Clinical guidance on the identification and management of treatment-resistant schizophrenia. J Clin Psychiatry. 2019;80(2). PMID: 30840788
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Leucht S, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia. Lancet. 2013;382(9896):951-962. PMID: 23810019
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. It does not replace professional medical judgement.