Psychiatry: Psychosis and schizophrenia

• Psychosis and schizophrenia: Psychosis — Overview | Schizophrenia — Features | Causes and Risk Factors | First-Episode Psychosis | Course and Relapse
• Treatment: Choosing and Starting Antipsychotics | Antipsychotic Side Effects | Movement Side Effects | Clozapine | Long-acting Injectable Antipsychotics | Psychological and Social Treatments
• Other psychoses: Schizoaffective, Delusional and Brief Psychotic Disorders | Drug-induced Psychosis | Psychosis From Physical Illness | Psychosis in Older People | Catatonia
• Revision: Drug Reference Table | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🌀 Psychosis and schizophrenia — psychosis means losing touch with reality: hallucinations, delusions and disorganised thinking. Early treatment through early intervention services improves outcomes. Antipsychotics work well for positive symptoms but have important side effects — especially weight gain and metabolic problems, movement disorders, and with clozapine, agranulocytosis and myocarditis.
Your four questions for every patient: Is this primary psychosis, or caused by drugs or a physical illness? Is the person safe (suicide, violence, self-neglect, command hallucinations)? Which antipsychotic suits them best, and what are its risks? Are their physical health and social needs being met?

Psychosis — Overview

• Key symptoms:
  • Hallucinations — perceptions without a stimulus; auditory is the commonest in schizophrenia (voices commenting, discussing, commanding); visual suggests an organic cause (delirium, drugs, Lewy body dementia).
  • Delusions — fixed, false beliefs held with certainty, not explained by culture — persecutory (the commonest), reference, grandiose, control, religious, jealousy, erotomanic, nihilistic, somatic.
  • Thought disorder — disorganised speech (loosening of associations, neologisms, word salad).
  • Disorganised or bizarre behaviour; catatonia.
• Causes:
  • Primary psychiatric — schizophrenia, schizoaffective disorder, delusional disorder, brief psychotic disorder, bipolar disorder (mania), psychotic depression, postpartum psychosis.
  • Drugs — cannabis, stimulants, hallucinogens, alcohol (withdrawal and hallucinosis), prescribed drugs (steroids, levodopa).
  • Physical illness — delirium, dementia, epilepsy, encephalitis, brain tumours, endocrine and metabolic disorders.
• Lifetime risk of schizophrenia — about 1%; onset usually late teens to early 30s (men earlier than women).

Schizophrenia — Features

• Diagnosis (ICD-11) — characteristic symptoms for at least 1 month, not due to another condition, drugs or a mood disorder.
• Positive symptoms (added experiences):
  • Hallucinations — especially third-person auditory hallucinations, running commentary, thought echo.
  • Delusions — persecutory, reference, control; often bizarre.
  • Thought alienation — thought insertion, withdrawal, broadcasting.
  • Passivity — actions, feelings or sensations controlled by an outside force.
  • Thought disorder.
• Negative symptoms (loss of normal function — often the most disabling and least responsive to drugs):
  • Flat or blunted affect.
  • Alogia (poverty of speech).
  • Avolition (lack of motivation), apathy.
  • Anhedonia; social withdrawal; self-neglect.
• Cognitive symptoms — poor attention, memory and executive function.
• Prodrome — months to years of social withdrawal, falling performance at school or work, odd beliefs, suspiciousness, poor self-care, anxiety and low mood before the first episode. "At-risk mental state" — refer to early intervention; CBT.
• Associated problems — depression, suicide (about 5% lifetime, highest early in the illness), substance misuse (cannabis, alcohol, tobacco), anxiety, unemployment, homelessness, physical illness.
• Violence — most people with schizophrenia are not violent; risk is increased with substance misuse, non-adherence and a history of violence; they are more often victims than perpetrators.

Causes and Risk Factors

• Genetics — strongly heritable (about 80%): general population about 1%; one parent with schizophrenia about 10%; both parents about 40%; identical twin about 40–50%. Many genes of small effect; 22q11.2 deletion (DiGeorge) raises risk greatly.
• Environmental:
  • Cannabis — especially high-potency ("skunk"), daily use, starting in adolescence.
  • Obstetric complications — hypoxia, prematurity, low birth weight, maternal infection; winter or spring birth.
  • Urban upbringing; migration and ethnic minority status (social adversity, discrimination).
  • Childhood adversity — abuse, trauma, bullying.
  • Older paternal age.
• Dopamine hypothesis:
  • Too much dopamine in the mesolimbic pathway — positive symptoms (antipsychotics block D2 receptors here).
  • Too little in the mesocortical pathway — negative and cognitive symptoms.
  • D2 blockade in the nigrostriatal pathway — extrapyramidal side effects.
  • D2 blockade in the tuberoinfundibular pathway — raised prolactin.
• Glutamate (NMDA receptor) dysfunction also contributes — ketamine and PCP cause psychosis; anti-NMDA receptor encephalitis mimics it.

First-Episode Psychosis

• Refer urgently to early intervention in psychosis (EIP) services (ages 14–65) — national standard: treatment within 2 weeks of referral. Don't start antipsychotics in primary care without specialist advice (unless urgent).
• Assessment:
  • Full history and MSE; collateral history; risk (suicide, harm to others, command hallucinations, self-neglect, vulnerability).
  • Drug and alcohol history — urine drug screen.
  • Physical examination — neurological signs, signs of drug use.
  • Bloods — FBC, U&E, LFTs, TFTs, calcium, glucose and HbA1c, lipids, prolactin, B12 and folate, CRP; consider HIV, syphilis, autoimmune encephalitis antibodies.
  • Baseline physical measures — weight, BMI, waist, pulse, BP.
  • ECG — before antipsychotics if cardiovascular risk, family history of sudden death, inpatient, or a drug with QT risk.
  • MRI brain and EEG if atypical features (neurological signs, confusion, seizures, older age).
• Treatment (NICE CG178):
  • Oral antipsychotic (chosen with the person) plus CBT for psychosis (CBTp) and family intervention.
  • Support for education and employment (Individual Placement and Support), physical health programmes, carer support.
  • Continue antipsychotic for at least 1–2 years after a first episode (relapse risk is high if stopped early).

Course and Relapse

• Course — variable: some recover fully after one episode; many have relapses with partial recovery; some have persistent symptoms and disability.
• Better prognosis — sudden onset, older age at onset, clear trigger, prominent mood symptoms, good premorbid functioning, female, married, good social support, short duration of untreated psychosis, good early response.
• Worse prognosis — gradual onset, young age at onset, prominent negative symptoms, poor premorbid functioning, cognitive impairment, substance misuse, long duration of untreated psychosis, family history, male.
• Relapse triggers — stopping medication (the biggest cause), cannabis and other drugs, stress, high "expressed emotion" in families (criticism, hostility, over-involvement).
• Relapse prevention — adherence support (consider long-acting injectables), family intervention, early warning signs plan, avoid cannabis, regular review.
• Mortality — life expectancy 15–20 years shorter (cardiovascular disease, smoking, diabetes, suicide).

Choosing and Starting Antipsychotics

• Choice — no antipsychotic (except clozapine) is clearly more effective; choose by side effect profile, patient preference, past response and physical health.

• Starting — start at a low dose and titrate; an adequate trial is 4–6 weeks at an optimum dose; avoid high doses and combining antipsychotics (except during switching, or clozapine augmentation).
• Monitoring (NICE CG178):
  • Weight — weekly for 6 weeks, then at 12 weeks, at 1 year, then yearly.
  • Waist, pulse and BP — at 12 weeks, 1 year, then yearly.
  • HbA1c or glucose and lipids — at 12 weeks, 1 year, then yearly.
  • Prolactin (if symptoms), ECG (if indicated), movement disorders, adherence, side effects.
• Metabolic management — diet and exercise programmes; switch to a drug with fewer metabolic effects (e.g. aripiprazole); consider metformin; treat diabetes, lipids and BP; stop smoking.

Antipsychotic Side Effects

• Metabolic — weight gain, type 2 diabetes, dyslipidaemia (worst with clozapine and olanzapine; least with aripiprazole, lurasidone).
• Hyperprolactinaemia (risperidone, amisulpride, haloperidol) — galactorrhoea, gynaecomastia, amenorrhoea, infertility, sexual dysfunction, osteoporosis; switch or add low-dose aripiprazole.
• Cardiac — QT prolongation (haloperidol, amisulpride, quetiapine at higher doses) — torsades de pointes and sudden death; check ECG, potassium and magnesium, avoid other QT drugs; myocarditis (clozapine).
• Anticholinergic — dry mouth, blurred vision, constipation, urinary retention, confusion.
• Alpha-blockade — postural hypotension, falls (quetiapine, clozapine, chlorpromazine).
• Sedation (quetiapine, olanzapine, clozapine).
• Sexual dysfunction.
• Lower seizure threshold (especially clozapine).
• Blood problems — neutropenia and agranulocytosis (clozapine, rarely others).
• VTE risk.
• Neuroleptic malignant syndrome — rare, life-threatening (see the Psychiatric Emergencies chapter).
• Older people with dementia — antipsychotics increase stroke risk and death; use only for severe distress or risk, short term, at low doses (risperidone is licensed for up to 6 weeks for persistent aggression in Alzheimer's).
• Parkinson's disease and Lewy body dementia — severe sensitivity to antipsychotics (rigidity, falls, NMS); avoid typical antipsychotics; quetiapine or clozapine (specialist) if essential.

Movement Side Effects

💡 Clinical Pearl: A young man given IM haloperidol who later can't stop his eyes rolling upwards, or develops a twisted neck, has acute dystonia — not a seizure or a "behaviour". It is frightening and painful, and responds within minutes to IM or IV procyclidine.

Clozapine

• Uses — treatment-resistant schizophrenia: no adequate response to at least two different antipsychotics (at least one non-clozapine second-generation) at adequate dose and duration. Effective in about half to two-thirds of these patients; also reduces suicide.
• Before starting — register with a clozapine monitoring service; baseline FBC (normal neutrophils), ECG, troponin, CRP, weight, BMI, BP, glucose and lipids.
• Blood monitoring (neutropenia and agranulocytosis):
  • FBC weekly for 18 weeks, then every 2 weeks until 1 year, then every 4 weeks.
  • "Traffic light" results — red (low neutrophils) means stop clozapine.
  • Patients must report sore throat, fever or infection urgently — check FBC.
• Serious side effects:
  • Agranulocytosis (about 1%, mostly in the first 18 weeks).
  • Myocarditis (first 2 months — fever, tachycardia, chest pain, breathlessness; troponin, CRP) and later cardiomyopathy.
  • Constipation and gut hypomotility — can cause bowel obstruction, perforation and death; ask at every review; prescribe laxatives proactively.
  • Seizures (dose-related).
  • Weight gain, diabetes, dyslipidaemia.
  • Hypersalivation (especially at night) — hyoscine hydrobromide.
  • Sedation, postural hypotension, tachycardia, fever early on, urinary incontinence, pneumonia (aspiration).
• Interactions and levels:
  • Smoking (not nicotine) induces clozapine metabolism — stopping smoking (e.g. on admission) can double levels (toxicity — sedation, seizures); restarting smoking lowers levels.
  • Infection and inflammation raise levels.
  • Erythromycin, ciprofloxacin, fluvoxamine raise levels; carbamazepine (avoid — agranulocytosis) lowers them.
  • Check plasma levels when needed.
• Missed doses — if more than 48 hours are missed, restart from a low dose and titrate again (risk of severe hypotension and collapse).
• Admission to hospital — make sure clozapine is continued (don't let it lapse), and check FBC, levels and bowels.

⚠️ Safety Pearl: A patient on clozapine with a sore throat or fever needs an urgent FBC (agranulocytosis). Constipation is also a killer — always ask about bowels, and remember that stopping smoking on admission can make clozapine levels rise dangerously.

Long-acting Injectable Antipsychotics

• Uses — people who prefer them, or have poor adherence to tablets and frequent relapses; also when medication is given under the Mental Health Act or a CTO.
• Examples — aripiprazole (monthly or 2-monthly), paliperidone (monthly, 3-monthly or 6-monthly), risperidone, olanzapine embonate, and first-generation depots — haloperidol decanoate, flupentixol decanoate, zuclopenthixol decanoate.
• Before starting — establish tolerability with the oral form first; test dose for first-generation depots.
• Olanzapine embonate — risk of post-injection delirium/sedation syndrome — observe for 3 hours after each injection.
• Benefits — certainty of adherence, regular contact with services, lower relapse rates.
• Zuclopenthixol acetate ("Acuphase") — a short-acting (2–3 days) injection sometimes used in acute disturbance (specialist; not for antipsychotic-naive patients).

Psychological and Social Treatments

• CBT for psychosis (CBTp) — at least 16 sessions; helps people make sense of and cope with voices and beliefs; reduces distress.
• Family intervention — at least 10 sessions over 3–12 months; reduces relapse and admission (lowers expressed emotion).
• Arts therapies — especially for negative symptoms.
• Individual Placement and Support — supported employment.
• Housing, benefits and social care; peer support; recovery colleges.
• Physical health — healthy lifestyle programmes, stop-smoking support, annual health checks.
• Care coordination — community mental health team; crisis plans; advance statements.
• Carers — carer's assessment, information and support.

Schizoaffective, Delusional and Brief Psychotic Disorders

• Schizoaffective disorder — symptoms of schizophrenia and a mood episode (mania or depression) at the same time, in the same episode; treated with antipsychotics plus mood stabilisers or antidepressants.
• Delusional disorder — one or more non-bizarre delusions for at least 3 months, with otherwise normal functioning and few other psychotic symptoms; middle to older age:
  • Types — persecutory, jealous (Othello syndrome — risk of violence to the partner), erotomanic (de Clérambault's syndrome — belief that a famous or higher-status person loves them; stalking), somatic (e.g. delusional parasitosis — belief of infestation with insects; brings "specimens"), grandiose.
  • Often poor insight; antipsychotics help some; engage through a supportive relationship.
• Acute and transient (brief) psychotic disorder — sudden onset of psychosis (often after stress) lasting days to weeks, with full recovery (under 3 months).
• Schizotypal disorder — eccentric behaviour, odd beliefs and speech, social anxiety, without clear psychosis; related to schizophrenia.
• Shared psychotic disorder (folie à deux) — a delusion transferred from one person to a close other; separate them.
• Capgras syndrome — belief that a familiar person has been replaced by an identical impostor (schizophrenia, dementia, brain injury).

Drug-induced Psychosis

• Cannabis — acute paranoia and hallucinations; regular high-potency use roughly doubles to quintuples the risk of schizophrenia; synthetic cannabinoids ("spice") cause severe psychosis, agitation and seizures.
• Stimulants — amphetamines, methamphetamine, cocaine: paranoia, tactile hallucinations ("formication" — insects under the skin), aggression, stereotyped behaviour.
• Hallucinogens — LSD, psilocybin (magic mushrooms), ketamine, PCP; flashbacks.
• Alcohol — alcoholic hallucinosis (auditory hallucinations in clear consciousness in heavy drinkers), delirium tremens (visual hallucinations, confusion in withdrawal), Wernicke–Korsakoff.
• Prescribed drugs — corticosteroids, levodopa and dopamine agonists, anticholinergics, antimalarials (mefloquine), isotretinoin, interferon, efavirenz, opioids (in older people), anabolic steroids.
• Management — stop the drug; supportive care; benzodiazepines for agitation; antipsychotics if persistent; usually resolves within days to weeks — persistence suggests a primary psychotic disorder (many later develop schizophrenia or bipolar disorder).

Psychosis From Physical Illness

• Clues — visual, tactile or olfactory hallucinations; confusion or fluctuating consciousness; first episode after 40; abnormal neurological signs; physical illness; no family or past history; poor response to antipsychotics.
• Causes:
  • Delirium — infection, drugs, metabolic.
  • Dementia — especially Lewy body dementia (vivid visual hallucinations, fluctuating cognition, parkinsonism) and Alzheimer's disease.
  • Epilepsy — temporal lobe epilepsy (ictal or post-ictal psychosis).
  • Autoimmune encephalitis (anti-NMDA receptor — young women; ovarian teratoma), HSV encephalitis, HIV, neurosyphilis.
  • Brain tumours, stroke, head injury, MS, Huntington's disease, Wilson's disease.
  • Endocrine and metabolic — thyroid disease, Cushing's, hypercalcaemia, hypoglycaemia, porphyria, B12 deficiency, SLE.
• Parkinson's disease psychosis — visual hallucinations from dopaminergic drugs; reduce drugs where possible; quetiapine or clozapine; avoid haloperidol and risperidone.
• Charles Bonnet syndrome — vivid, complex visual hallucinations in people with visual loss (e.g. macular degeneration), with insight; reassure.

Psychosis in Older People

• Very late-onset schizophrenia-like psychosis — onset after 60; more in women, people living alone, with hearing or visual impairment; persecutory delusions (neighbours, intruders — "partition delusions"); few negative symptoms.
• Always exclude delirium, dementia, depression with psychosis, drugs, sensory loss.
• Management — correct hearing and vision; social support; low-dose antipsychotics (higher sensitivity to side effects — falls, postural hypotension, EPS, stroke risk); monitor closely.
• Behavioural and psychological symptoms of dementia — see the Dementia chapter (non-drug approaches first).

Catatonia

• What it is: A syndrome of abnormal movement and behaviour — seen in mood disorders (most commonly), schizophrenia, autism, and medical illness (encephalitis, NMS, metabolic).
• Features — stupor (immobile, unresponsive), mutism, posturing, waxy flexibility (limbs stay where placed), negativism, staring, echolalia and echopraxia (copying speech or movements), stereotypies, withdrawal (refusing food and drink).
• Assessment — Bush–Francis Catatonia Rating Scale; exclude NMS (CK, temperature, autonomic instability), encephalitis, non-convulsive status (EEG), stroke.
• Risks — dehydration, AKI, VTE, pressure sores, aspiration, malignant catatonia (fever, autonomic instability — life-threatening).
• Treatment — lorazepam (a "lorazepam challenge" often produces rapid improvement — also diagnostic); ECT if lorazepam fails or in malignant catatonia; supportive care (fluids, VTE prophylaxis); avoid antipsychotics in the acute phase (risk of NMS).

Drug Reference Table

Spot the Diagnosis

Exam-style Scenarios

1. A 20-year-old man is brought in by his parents. He has stopped going to university, believes his phone is being hacked by the government, and hears voices discussing him. He smokes cannabis daily.
Answer: First-episode psychosis (possible schizophrenia; cannabis a contributing factor).

• Risk assessment; urgent referral to early intervention in psychosis.
• Bloods, urine drug screen, ECG; physical examination; consider MRI if atypical features.
• Oral antipsychotic (chosen with him — e.g. aripiprazole), CBTp, family intervention, and help to stop cannabis.

2. A 35-year-old woman with schizophrenia has not responded to adequate trials of olanzapine and risperidone.
Answer: Treatment-resistant schizophrenia — offer clozapine.

• Register with a monitoring service; baseline FBC, ECG, troponin, CRP, metabolic measures.
• Slow titration; FBC weekly for 18 weeks; watch for myocarditis in the first 2 months.
• Prevent constipation; warn about sore throat and fever; smoking affects levels.

3. A 45-year-old man on clozapine is admitted with pneumonia and stops smoking in hospital. Two days later he is very drowsy and has a seizure.
Answer: Clozapine toxicity (stopping smoking and infection both raise levels).

• Withhold or reduce clozapine; check plasma clozapine level, FBC and ECG.
• Treat the infection and seizure; discuss with psychiatry and pharmacy.
• Restart at an adjusted dose; nicotine replacement doesn't affect clozapine metabolism.

4. An 18-year-old woman is given IM haloperidol for agitation. Three hours later her eyes are fixed upwards and her neck is twisted to one side.
Answer: Acute dystonic reaction.

• Procyclidine IM or IV — works within minutes.
• Consider short-term oral procyclidine; review the antipsychotic choice.
• Explain to the patient — it's frightening and may affect future adherence.

5. A 30-year-old man with schizophrenia has gained 15 kg on olanzapine. HbA1c is 50 mmol/mol.
Answer: Antipsychotic-induced weight gain and type 2 diabetes.

• Lifestyle programme; consider switching to aripiprazole (or lurasidone) with specialist input.
• Metformin; treat lipids and BP; stop-smoking support.
• Annual (and 12-week after changes) physical health monitoring.

Key Points

• Visual hallucinations suggest an organic cause; auditory hallucinations are typical of schizophrenia.
• Schizophrenia: positive, negative and cognitive symptoms; lifetime risk about 1%.
• Cannabis (especially skunk) raises the risk of schizophrenia.
• First-episode psychosis: refer to EIP (treatment within 2 weeks); antipsychotic plus CBTp and family intervention.
• Baseline and regular weight, waist, BP, pulse, HbA1c, lipids, prolactin and ECG if indicated.
• Choose antipsychotics by side effects: aripiprazole (less weight, lower prolactin), olanzapine (weight, diabetes), risperidone (prolactin), haloperidol (EPS, QT).
• Acute dystonia (hours) — procyclidine; akathisia (days) — propranolol; parkinsonism (weeks); tardive dyskinesia (years) — stop anticholinergics.
• Clozapine after two failed antipsychotics: FBC weekly 18 weeks, 2-weekly to 1 year, then 4-weekly.
• Clozapine dangers: agranulocytosis, myocarditis, constipation, seizures; smoking changes levels; retitrate if over 48 hours missed.
• Long-acting injections help adherence; olanzapine depot needs 3 hours of observation.
• Antipsychotics in dementia raise stroke and death risk; avoid in Lewy body dementia and Parkinson's.
• Delusional disorder: single non-bizarre delusion for 3 months with preserved function.
• Catatonia: lorazepam first, ECT if needed; avoid antipsychotics acutely.

Guidelines and Further Reading

• NICE CG178: Psychosis and schizophrenia in adults — prevention and management
• NICE QS80: Psychosis and schizophrenia in adults
• NHS England: Early intervention in psychosis access and waiting time standard
• Maudsley Prescribing Guidelines in Psychiatry
• MHRA: Clozapine — reminder of potentially fatal risk of intestinal obstruction, faecal impaction and paralytic ileus
• Lester UK Adaptation: Positive Cardiometabolic Health Resource
• NICE NG97: Dementia (antipsychotic use)
• BNF — for current doses