Psychosis and schizophrenia
Exam Tips
- In OSCEs, prioritise risk: ask directly about command hallucinations, self-harm, suicidal ideation, and risk to others, then assess capacity and safeguarding.
- Differentiate positive from negative symptoms clearly; examiners often reward explicit examples such as thought insertion/withdrawal/broadcasting and avolition/blunted affect.
- State that first-episode psychosis needs urgent Early Intervention referral and baseline physical/ECG/metabolic work-up before and during antipsychotic treatment.
- For viva questions on poor response, mention adherence, substance use, correct diagnosis, and when to escalate to clozapine with mandatory blood monitoring.
- Use a mechanistic framework in SAQs: mesolimbic dopamine excess for positive symptoms, mesocortical deficits for negative/cognitive symptoms; reference a dopamine-pathway figure from your psychiatry core text.
Definition
Psychosis is a clinical syndrome in which reality testing is impaired, producing symptoms such as hallucinations, delusions, and disordered thought, with associated behavioural and functional decline. Schizophrenia is the commonest primary psychotic disorder and is diagnosed when characteristic psychotic symptoms (with at least one core psychotic feature) persist for at least 1 month and are not better explained by mood disorder, substances, or organic disease.
Pathophysiology
Schizophrenia is best understood as a neurodevelopmental-spectrum disorder with strong heritability and environmental loading. Current models combine dopaminergic dysregulation (mesolimbic hyperdopaminergia linked to positive symptoms; mesocortical hypodopaminergia linked to negative/cognitive symptoms), glutamatergic dysfunction (especially NMDA-related signalling), and aberrant salience processing, leading neutral stimuli to be misinterpreted as highly meaningful. Structural and network-level changes (cortical thinning, hippocampal and connectivity abnormalities) are thought to evolve from early vulnerability plus later stressors, substance exposure, and social adversity. For revision diagrams, see a standard psychiatry textbook figure on dopamine pathways (mesolimbic/mesocortical/nigrostriatal/tuberoinfundibular circuits).
Risk Factors
- Family history/genetic loading (high heritability; markedly increased risk with an affected parent)
- Stressful life events (bereavement, relationship breakdown, eviction, job loss)
- Childhood adversity (abuse, bullying, parental separation/loss)
- Cannabis use (higher risk with frequent use, adolescent onset, and high-THC products)
- Other psychoactive substances (amphetamine, cocaine, ketamine, LSD, volatile inhalants)
- Migration and minority ethnic background in UK epidemiology (higher observed incidence in some groups)
- Urban upbringing/living
- Perinatal and early-life insults (maternal infection/stress, nutritional deficiency, growth restriction, birth trauma)
- Extremes of parental age (younger parents and older paternal age)
- High-dose corticosteroid exposure
- Toxoplasma gondii exposure
Clinical Features
Symptoms
- Auditory hallucinations (voices commenting, arguing, commanding, or echoing thoughts)
- Delusions (persecutory, referential, grandiose, passivity phenomena)
- Thought interference (thought insertion, withdrawal, broadcasting)
- Disordered thought and speech (loosening of associations, derailment, neologisms)
- Negative symptoms: avolition, anhedonia, reduced speech, emotional blunting, social withdrawal
- Cognitive change: poor attention, memory and executive dysfunction
- Prodromal decline in functioning, sleep disturbance, and increasing suspiciousness/distress
Signs
- Blunted or incongruent affect
- Poverty of speech and psychomotor slowing
- Disorganised or bizarre behaviour impairing goal-directed activity
- Catatonic signs (posturing, mutism, negativism, stupor, waxy flexibility)
- Self-neglect and reduced personal care
- Agitation during acute episodes
Investigations
Management
Lifestyle Modifications
- Rapid referral to Early Intervention in Psychosis services for first-episode psychosis
- Psychoeducation for patient and family; relapse-signature planning and crisis/safety plan
- CBT for psychosis and family intervention where available
- Address cannabis and other substance misuse; smoking cessation support
- Sleep regularisation, structured daily activity, social/occupational rehabilitation
- Active cardiometabolic risk reduction: diet, exercise, weight monitoring, BP/lipids/glucose checks
Pharmacological Treatment
Second-generation antipsychotics (first-line in many UK settings, individualised choice)
- Risperidone oral usually start 1-2 mg daily; typical target 4-6 mg daily
- Olanzapine oral usually start 5-10 mg at night; usual range 5-20 mg daily
- Aripiprazole oral start 10-15 mg daily; usual range 10-30 mg daily
- Quetiapine oral titrated from 50 mg day 1 to around 300 mg by day 4; usual 300-450 mg daily in divided doses (range up to 750 mg daily)
Start low and titrate using shared decision-making. Monitor for weight gain, dyslipidaemia, diabetes risk, sedation, orthostatic hypotension, sexual dysfunction, and hyperprolactinaemia (especially risperidone/amisulpride). Warn about impaired driving/sedation and alcohol potentiation.
First-generation antipsychotic option
- Haloperidol oral often 0.5-5 mg two or three times daily, adjusted to response and tolerability
Useful in selected cases but higher EPS risk (acute dystonia, parkinsonism, akathisia, tardive dyskinesia). Check QTc and avoid combining multiple QT-prolonging drugs when possible.
Treatment-resistant schizophrenia
- Clozapine oral start 12.5 mg once or twice on day 1, then gradual titration (commonly to 200-450 mg daily; max 900 mg daily in divided doses)
Indicated after inadequate response to at least two antipsychotics (one usually non-clozapine SGA). Mandatory blood monitoring for neutropenia/agranulocytosis; serious warnings include myocarditis, cardiomyopathy, seizures, severe constipation/ileus, and venous thromboembolism. Stop and urgently assess if fever, chest pain, breathlessness, or bowel obstruction symptoms occur.
Acute behavioural disturbance in psychosis (specialist protocol-driven)
- Lorazepam 1-2 mg oral/IM as needed
- Haloperidol 5 mg IM (often with promethazine 25-50 mg IM where locally recommended)
Use de-escalation first. Observe airway, respiration, and sedation level closely; avoid excessive cumulative benzodiazepine dosing, especially with intoxication or respiratory compromise.
Complications
- Suicide (lifetime risk around 5%, highest near illness onset and after relapses)
- Premature mortality (approximately 15 years earlier than general population on average)
- Cardiovascular disease and metabolic syndrome (part illness-related, part treatment-related)
- Type 2 diabetes and dyslipidaemia
- Smoking-related disease
- Infections including blood-borne viruses in those with substance misuse
- Sexual dysfunction (libido, erectile, ejaculatory, orgasmic, menstrual disturbance)
- Social exclusion, unemployment, and functional decline
- Relapse, treatment resistance, and persistent negative symptoms
Prognosis
Course is variable: many patients improve with combined pharmacological and psychosocial treatment, but relapse over years is common. Around four in five show some response within a year, while a substantial minority develop treatment resistance (roughly one quarter early, up to one third across illness course). Poorer outcomes are linked to longer duration of untreated psychosis, early/insidious onset, male sex, prominent negative symptoms, ongoing substance misuse, and social disadvantage.
Sources & References
🏥BMJ Best Practice(1)
💊BNF Drug References(10)
- Aripiprazole[management.pharmacological]
- Cariprazine[management.pharmacological]
- Cytisinicline[cautions]
- Levomepromazine[management.pharmacological]
- Linezolid[cautions]
- Lurasidone hydrochloride[management.pharmacological]
- Paliperidone[management.pharmacological]
- Pimozide[management.pharmacological]
- Quetiapine[management.pharmacological]
- Risperidone[management.pharmacological]
✅NICE Guidelines(1)
- Psychosis and schizophrenia[overview]