Schizophrenia and other psychotic disorders

• Schizophrenia is a chronic psychotic disorder marked by positive symptoms (delusions, hallucinations, disorganised speech and behaviour), negative symptoms (reduced expression, motivation, pleasure and social drive) and cognitive impairment.
• It affects roughly 1 in 300 people worldwide and usually begins in late adolescence or early adulthood, somewhat earlier in men. ^[1]
• The other disorders on this page (brief psychotic disorder, schizophreniform disorder, schizoaffective disorder, delusional disorder) form a spectrum defined mainly by which symptoms are present and how long they last.
• Care starts with a full assessment and a therapeutic trial of a single antipsychotic at a low dose, combined with cognitive behavioural therapy and family intervention. ^[2][3]
• For treatment-resistant illness, clozapine is the drug with the best evidence; for catatonia, benzodiazepines (usually lorazepam) are first line and electroconvulsive therapy is the next step. ^[2][7]

By the end of this page you should be able to:

1. Define schizophrenia and the related psychotic disorders and explain how they differ by symptom type and duration.
2. Describe the positive, negative and cognitive symptom clusters and link each to its brain mechanism.
3. Recognise the mental-state and risk-assessment findings that matter most in the first episode.
4. Plan investigations before and during antipsychotic treatment, including baseline tests and monitoring intervals.
5. Choose and titrate an antipsychotic, and decide when to refer for clozapine, a long-acting injection, or clozapine augmentation.
6. Recognise and treat catatonia safely and plan relapse prevention for the first two years.

The older word "psychosis" describes a syndrome, not a diagnosis: a loss of contact with reality in which a person holds fixed false beliefs (delusions), perceives things that are not present (hallucinations), speaks in a jumbled way, or behaves in a markedly disorganised or catatonic fashion. Several disorders share these features and are grouped in the "schizophrenia spectrum and other psychotic disorders". They are separated from mood disorders by the relative importance of mood episodes and separated from each other by duration and symptom profile. ^[5]

Schizophrenia itself is diagnosed when symptoms persist long enough to make the disorder clearly chronic. Brief psychotic disorder covers an episode from 1 day to under 1 month. Schizophreniform disorder covers the same symptom picture lasting 1 to under 6 months. Schizoaffective disorder requires a major mood episode (depression or mania) running alongside psychosis for most of the illness, with a period of psychosis without prominent mood symptoms. Delusional disorder requires persistent delusions for at least 1 month without the other core schizophrenia symptoms such as disorganised speech or marked hallucinations, and without a major mood episode. ^{[10] [5]}

These distinctions matter in practice: a person in the first weeks of illness is not called schizophrenia, and treatment should not be decided by a label alone. The initial management of any first episode (see the management section and flowchart) is similar, while the expected course and longer-term prognosis differ. ^[2]

Schizophrenia affects approximately 1 in 300 people worldwide, about 0.29% (27 million people), rising to 1 in 206 (0.49%) among adults aged 20 years or over. It is less common than many other mental disorders but causes a large share of disability because it usually starts in early adult life and persists. ^[1] Around 1% of people develop schizophrenia over a lifetime in most settings. ^[5][6]

Onset is most often in late adolescence and the twenties, and it tends to occur earlier in men than in women. ^[1] Men usually present in their early to mid-twenties and women in their late twenties, although late-onset illness is well recognised and childhood onset is rare. ^[5][6]

The illness is associated with a shorter life: people with schizophrenia die roughly 9 years earlier than the general population, largely from cardiovascular, metabolic and infectious disease rather than from the psychiatric illness itself. ^[1]

Access to care remains the biggest global problem. Approximately 50% of people in mental hospitals carry a schizophrenia diagnosis, yet only 29% of people with psychosis receive specialist mental health care. ^[1][4] At least one in three people with schizophrenia achieve complete remission of symptoms. ^[1]

No single cause has been identified. Schizophrenia is best understood as the result of a genetic liability combining with environmental exposures, superimposed on a neurodevelopmental vulnerability that unfolds over years. ^[1][6]

Genetic and developmental. Family history increases risk strongly. Twin and family studies support a polygenic (many genes, each of small effect) basis rather than one inherited gene. Prenatal and early exposures such as maternal infection, perinatal complications, advanced paternal age, and early childhood adversity are repeatedly associated with later illness, although none is sufficient on its own. ^[6]

Environmental and substance use. Heavy cannabis use is associated with an elevated risk of schizophrenia; the association is strongest with high-potency products and with use in early adolescence. ^[1] Urban living, migration (particularly to a country where the person is in a minority), childhood trauma, and chronic social adversity also raise risk. Protective and modifying factors include strong family support and timely treatment. ^[6]

Risk of comorbidity. People with psychosis or schizophrenia have high rates of tobacco and substance use, both of which worsen symptoms and shorten life. Smoking in particular slows the metabolism of clozapine and olanzapine, so any change in smoking (including stopping) can sharply alter drug levels. ^[2]

Stigma is itself a treatment hazard: it discourages help-seeking and is linked to poorer outcomes, so a recovery-oriented, person-centred approach is part of evidence-based care. ^[1][4]

Understanding the symptoms is easier once the brain mechanisms are mapped onto them. ^[6]

The dopamine pathways. The central model is dopaminergic dysregulation. There are five main dopamine pathways, and two matter most for symptoms:

• The mesolimbic pathway runs from the ventral tegmental area to limbic regions including the nucleus accumbens and mediates reward and salience. Its overactivity is linked to positive symptoms such as delusions and hallucinations. ^[6]
• The mesocortical pathway projects to the prefrontal cortex and regulates executive function, working memory and affect. Its underactivity is linked to negative and cognitive symptoms. ^[6]
• The nigrostriatal pathway controls movement; blocking dopamine here produces the extrapyramidal side effects of antipsychotics. ^[6]
• The tuberoinfundibular pathway tonically inhibits prolactin, so blocking it raises serum prolactin and can cause galactorrhoea and sexual dysfunction. ^[6]

Drugs containing D2 antagonists are effective because they dampen the overactive mesolimbic pathway; the clinical improvement lags behind peak receptor occupancy by roughly 2 to 4 weeks, so an adequate trial takes time. ^[6] Positive symptoms also improve faster and more completely than negative and cognitive ones, because the latter arise more from mesocortical hypofunction and from structural brain changes (loss of grey matter volume and, in some models, excessive synaptic pruning during adolescence). ^[6]

Beyond dopamine. Modern models add glutamatergic failure, particularly NMDA receptor hypofunction in prefrontal circuits; reduced GABA output from parvalbumin-positive interneurons; serotonergic and cholinergic disturbance; and circuit-level "dysconnectivity" between cortex, thalamus and striatum. These strands converge on an excitation-inhibition imbalance in cortical microcircuits. ^[6] Immune and inflammatory mechanisms are implicated in some subgroups, which is one reason researchers are testing anti-inflammatory treatments as adjuncts, but these are not standard care. ^[6]

General anaesthesia and structural imaging changes have long been documented, but no blood test or scan can diagnose schizophrenia; diagnosis remains clinical after ruling out secondary causes. ^[5]

Patients rarely say "I have schizophrenia". They and their families describe a change. A useful way to organise the history is by the three symptom clusters.

Positive symptoms (things added to normal experience).

• Delusions. Firm, unshakeable beliefs that are out of keeping with the person's culture and the evidence: persecution, reference, grandeur, control, thought insertion or broadcasting, passivity. ^[1][5]
• Hallucinations. False perceptions. Auditory hallucinations (hearing voices, often commenting or commanding) are the most common; visual, tactile, olfactory and gustatory hallucinations also occur. ^[1][5]
• Disorganised speech. Loosening of associations, tangentiality, incoherence, or "word salad"; in severe cases speech is scanty or mute. ^[5]
• Disorganised or catatonic behaviour. Bizarre or purposeless acts, unpredictable or inappropriate emotional responses, bizarre postures, waxy flexibility, stupor, or extreme agitation. ^[1][5]

A prodrome often precedes the first clear episode by months to years: social withdrawal, odd ideas, sleep disturbance, irritability, declining performance at work or study, and subtle cognitive changes. ^[5]

Negative symptoms (things taken away from normal experience). These are often the most disabling long-term:

• Affective flattening: reduced range and intensity of emotional expression.
• Alogia: reduced fluency and amount of speech.
• Avolition: reduced motivation, initiative and energy; difficulty starting and sustaining activities.
• Anhedonia: reduced ability to experience pleasure.
• Asociality: reduced interest in relationships. ^[1][5]

Cognitive symptoms. Deficits in attention, processing speed, working memory, learning and memory, and executive function. These explain much of the functional disability of schizophrenia and are only modestly responsive to antipsychotics. ^[6]

Mood and insight. Depression is common and often follows a psychotic episode; anxiety and substance misuse are frequent. Insight into illness is commonly impaired, which is why some patients do not accept medication. ^[2][5]

There is no single physical sign. The examination aims to establish the diagnosis (through the mental state), exclude medical causes, and assess risk.

Mental state examination (MSE). Document systematically:

• Appearance and behaviour: self-care, eye contact, motor activity (retardation, agitation, stereotypies), catatonic signs.
• Speech: rate, volume, coherence, poverty.
• Mood and affect: flattened, incongruent, labile; note depression objectively.
• Thought: form (loosening, thought block, flight of ideas) and content (delusions, preoccupations, overvalued ideas).
• Perception: hallucinations and illusions; ask directly about voices and whether they are commanding or insulting.
• Cognition: attention, memory and executive function; use a simple screen (for example clock drawing, digit span) and, where available, formal neuropsychological testing.
• Insight: does the patient recognise that they are unwell and that treatment might help? ^[5]

Risk assessment. This is obligatory in every patient and should be repeated at every contact:

• Suicide. Schizophrenia carries a greatly elevated suicide risk; the highest-risk period is the first few years of illness and after discharge from hospital. ^[6] Ask about hopelessness, plans and means, and recent self-harm.
• Violence. Most patients are not violent, but risk rises with active positive symptoms, substance misuse, poor adherence, command hallucinations and a past history of violence. ^[2]
• Self-neglect and exploitation, financial abuse, and risk from third parties.
• Medical emergencies: dehydration, aspiration, deep vein thrombosis and the complications of immobility in catatonia. ^[7]

Physical examination. Baseline weight, height and body-mass index, pulse and blood pressure, cardiovascular and respiratory examination, neurological examination including movement disorder assessment, and a search for medical causes. ^[2]

The most common error is to call every psychosis "schizophrenia". The table lists the separations a student should be able to defend. ^[2][5]

There is no test that confirms schizophrenia. Investigations are used to exclude organic causes, to plan safe antipsychotic treatment, and to monitor metabolic and endocrine effects. NICE recommends structural neuroimaging is not used routinely in first-episode psychosis. ^[2]

In catatonia, add a metabolic panel, creatinine kinase and serum iron, and consider auto-immune, infective and neurological work-up because encephalitis and general medical conditions can present exactly this way. ^[7]

NICE sets out a specific, timed schedule that should be part of the prescription bundle. ^[2]

• Before starting: weight (charted), waist circumference, pulse and blood pressure, fasting blood glucose or HbA1c, blood lipid profile, serum prolactin, assessment of any movement disorder, and assessment of nutritional status, diet and physical activity. ^[2]
• ECG before starting if the summary of product characteristics requires it, if the physical examination shows cardiovascular risk (such as high blood pressure), if there is a personal history of cardiovascular disease, or if the person is being admitted as an inpatient. ^[2]
• During titration: document response, side effects, and movement disorders. ^[2]
• Weight: weekly for the first 6 weeks, then at 12 weeks, at 1 year and then annually. ^[2]
• Waist circumference: annually (charted). ^[2]
• Pulse and blood pressure: at 12 weeks, at 1 year and then annually. ^[2]
• Fasting glucose (or HbA1c) and lipids: at 12 weeks, at 1 year and then annually. ^[2]
• Physical health monitoring stays with the secondary care team for at least the first 12 months, or until the condition is stable, then may transfer to primary care with shared care. Primary care then continues at least annually. ^[2]

The diagnosis rests on history and examination. Paraphrasing DSM-5-TR: two (or more) of delusions, hallucinations, disorganised speech, grossly disorganised or catatonic behaviour, and negative symptoms, each present for a significant part of a month, with at least one from the first three; significant functional decline since onset; and continuous signs for at least 6 months, which must include at least 1 month of active-phase symptoms (possibly less if treated) and may include prodromal or residual symptoms. Schizophrenia is not diagnosed if the symptoms are better explained by a medical condition, substance or medication, or by a mood disorder with psychotic features; a history of autism spectrum disorder calls for the additional requirement of prominent delusions or hallucinations for at least 1 month. ^[5]

Severity and course specifiers. Rather than subtypes, DSM-5-TR specifies current state: first episode (in acute episode, in partial remission, or in full remission), multiple episodes, or continuous course, and severity (mild, moderate, severe). These are recorded after a year. ^[5]

Functional assessment. Document baseline occupational, educational, self-care and relational functioning. This is as important as the symptom count and is what recovery is measured against. ^[2]

The management section follows the typical sequence: acute stabilisation, then consolidation, then long-term recovery. It is adapted to the three guidelines named in the brief: NICE CG178 (last updated 4 September 2026), the APA Practice Guideline (3rd edition, 2020/2021), and WHO mhGAP (version 2.0). ^[2][3][4]

Acute psychosis is frightening and risky. The first tasks are safety, a calm environment and medical assessment, not medication alone.

• Assess urgently for risk of suicide, violence, self-neglect and medical compromise. ^[2]
• Place of care. Crisis resolution and home treatment teams are the first-line acute setting when available; otherwise admit to an age-, gender- and vulnerability-appropriate inpatient unit. ^[2]
• Start a comprehensive assessment (psychiatric, medical, psychological, social, developmental, occupational) and write a care plan with the service user. ^[2]
• Do not start antipsychotics in primary care without a consultant psychiatrist. ^[2]
• In an emergency (immediate risk to self or others), follow the NICE guidelines on violence and aggression and self-harm; rapid tranquillisation may be needed, with review of the episode afterwards. ^[2]

The first episode determines much of the long-term outcome, so early, full and persistent treatment matters.

Services. Early intervention in psychosis (EIP) services should be accessible to everyone with a first episode or first presentation, regardless of age or duration of untreated psychosis. People should be assessed without delay. ^[2] APA recommends structured coordinated specialty care for first-episode psychosis. ^[3] WHO mhGAP trains non-specialist clinicians in primary care to recognise psychosis, assess risk and start initial treatment in low-resource settings. ^[4]

Assessment. A full multidisciplinary assessment, including medical work-up to exclude organic brain disorders and medicines that may produce psychosis, plus assessment of trauma (post-traumatic stress is common and separate), other conditions (depression, anxiety, substance use) and coexisting neurodevelopmental conditions. ^[2]

Treatment. For first-episode psychosis, offer an oral antipsychotic together with psychological interventions: family intervention and individual cognitive behavioural therapy. ^[2] If the person wishes to try psychological intervention alone, advise that combination is more effective; if they decline medication, offer family intervention and CBT, agree a review within a month and monitor closely. ^[2]

There is no single "best" antipsychotic for schizophrenia in general. Effectiveness differences in trials are modest except for clozapine. Choice is therefore individual and shared, weighing which side effects the person is least willing to tolerate (metabolic, extrapyramidal, cardiovascular/QT, prolactin, subjective experience), coexisting medical conditions, and formulation. ^[2][3][6]

Principles. ^[2][3][6]

• Use one antipsychotic at a time at a low dose, titrated within the licensed range; do not combine antipsychotics except briefly while switching.
• Start at the lower end of the licensed range and titrate slowly; do not rapidly escalate doses ("rapid neuroleptisation"). ^[2]
• Judge efficacy after a trial of 4 to 6 weeks at an optimum dose; if there is less than about 20 to 25% improvement, reconsider diagnosis and adherence and consider switching. ^[2][6]
• Review benefits and side effects at least annually.
• Offer depot or long-acting injectable (LAI) antipsychotic where the person prefers it or where covert non-adherence is a clinical priority. ^[2] LAIs are associated with 30 to 50% fewer relapses and fewer rehospitalisations than equivalent oral treatment in many, though not all, analyses. ^[6]

Class differences that guide choice. First-generation agents (haloperidol, chlorpromazine, fluphenazine, perphenazine, trifluoperazine and others) block dopamine D2 strongly; they control positive symptoms well but carry a higher risk of extrapyramidal symptoms and tardive dyskinesia. Second-generation agents block D2 at moderate occupancy and add 5-HT2A antagonism, which improves neurological tolerability and modestly helps cognition, but most worsen metabolic risk (especially clozapine and olanzapine). ^[5][6]

Typical adult oral dose ranges (the prescriber should follow the product label and the local formulary; ranges include starting doses that may not be effective). ^[8]

Manage side effects proactively: treat acute dystonia with an anticholinergic; for parkinsonism reduce the dose, switch, or add an anticholinergic; for akathisia reduce the dose, switch, or add a benzodiazepine or beta-blocker; for moderate to severe or disabling tardive dyskinesia use a VMAT2 inhibitor; give antipsychotics that prolong QT (haloperidol, ziprasidone) with ECG monitoring; check weight, pulse, blood pressure, glucose and lipids on the schedule above. ^[2][3]

Clozapine is the only antipsychotic with consistent superiority for treatment-resistant schizophrenia and the only one that reduces suicide risk and (in large population studies) all-cause mortality. ^[6] NICE restricts it to people whose illness has not responded adequately despite sequential adequate doses of at least two different antipsychotics, at least one of which is a non-clozapine second-generation agent. ^[2] APA recommends clozapine for treatment-resistant schizophrenia and when suicide risk remains substantial despite other treatments; a further suggestion supports its use when aggression remains substantial despite other treatments. ^[3]

Before starting, rule out agranulocytosis risk factors and ensure the haematology monitoring programme (white cell and absolute neutrophil counts before starting and at guideline-defined intervals) is in place. Do not start if baseline neutrophils are below the local threshold. ^[6]

Dose. Start at 12.5 mg and titrate gradually toward a therapeutic range of roughly 300–600 mg daily, corresponding to plasma concentrations of 350–600 ng/mL. Titrate more slowly in older adults and in people with cardiovascular or hepatic disease. ^[6] StatPearls cites a licensed target of 150–300 mg twice daily for treatment-resistant illness. ^[5] Stopping abruptly risks rebound psychosis and, after prolonged use, a cholinergic rebound; any change should be gradual. ^{[2] [8]}

Monitoring. Haematological monitoring is mandatory: weekly absolute neutrophil counts for the first 6 months, then biweekly for the next 6 months, then monthly (programmes differ by country; the UK schedule is weekly for 18 weeks, fortnightly for a year, then monthly). ^[6] Also monitor weight, pulse, blood pressure, glucose and lipids, bowel habit, and (when indicated) plasma clozapine level. ^[2][6]

Adverse effects to actively prevent and detect. Agranulocytosis (rare but potentially fatal), myocarditis and cardiomyopathy, seizures, anticholinergic burden with severe constipation (which can be life-threatening), pneumonia and aspiration, sialorrhoea, orthostatic hypotension, sedation, weight gain and metabolic syndrome, and diabetes. Smoking increases clozapine metabolism; stopping smoking can cause toxicity. Reinforce this at every review. ^[2][6]

If clozapine response is inadequate, review diagnosis, adherence and dose, measure plasma levels, and only then augment (for example with aripiprazole or amisulpride), for up to 8 to 10 weeks, or with ECT. Choose the augmenting drug so it does not add to clozapine's common side effects. ^[2][6]

Catatonia is a severe motor syndrome (stupor, mutism, negativism, posturing or waxy flexibility, stereotypies, and either profound slowing or extreme excitement) that can occur in schizophrenia and in many other conditions. Its prevalence is about 10% among psychiatric inpatients. ^[7] A minority of catatonic patients (about 30%) have schizophrenia; most have a mood disorder. ^[7] Catatonia can also signal a general medical or neurological condition, including anti-NMDA receptor encephalitis, and can be drug-induced (neuroleptic malignant syndrome is considered by several experts to be a drug-induced form of catatonia). ^[7]

Malignant catatonia (catatonia with fever and autonomic instability) is life-threatening; the picture is close to neuroleptic malignant syndrome. ^[7]

Treatment. ^[7]

• Supportive first. Airway, fluids, nutrition, thromboprophylaxis, prevent aspiration and contractures. Complications (pneumonia, dehydration, pressure ulcers) are the usual cause of death. ^[7]
• Stop causative drugs. Discontinue antipsychotics in the acute catatonic state, because they can worsen it or precipitate neuroleptic malignant syndrome. ^[7]
• Benzodiazepines first line, regardless of underlying diagnosis. Use the lorazepam challenge to confirm and treat: give 1 or 2 mg intravenously, reassess in 5 minutes; if there is no change, give a second dose and reassess. Once catatonia responds, use repeated doses, most authors starting at 1 to 2 mg every 4 to 12 hours, and titrate upward; 8 to 24 mg lorazepam per day are common and are usually tolerated without sedation if increases are gradual. A response is usually seen within 3 to 7 days. ^[7]
• ECT when benzodiazepines fail or in life-threatening or malignant catatonia, or where the underlying illness warrants it. NICE reserves ECT for rapid short-term treatment of severe catatonia when other treatments have not worked or the condition is life-threatening. ^[2][7]
• Other options with reported benefit include zolpidem (10 mg oral, monitored response over 30 minutes; 7.5 to 40 mg daily for maintenance), and amantadine (100 to 500 mg three times daily) or memantine (5 to 20 mg daily). ^[7] Once catatonia improves, second-generation antipsychotics with low D2 affinity (quetiapine, olanzapine) or partial agonism (aripiprazole) may be introduced to target residual psychosis. ^{[7] [6]}

Catatonia associated with schizophrenia carries a worse prognosis than catatonia in mood disorders, and chronic catatonia can persist for years; nonetheless, treatment should be started promptly on detection. ^[7]

Medication alone is rarely enough for recovery. ^[2][3][6]

• Cognitive behavioural therapy for psychosis (CBTp) is recommended for all (APA strongly; NICE offers it for persisting or relapse-prevention needs). It is delivered one to one over at least 16 planned sessions, targeting links between thoughts, feelings and symptoms and developing coping. ^[2][3]
• Family intervention for at least 10 sessions, over 3 to 12 months, for families in close contact with the person. ^[2]
• Psychoeducation for the person and carers about the illness, treatment and early warning signs. ^[3]
• Arts therapies, assertive community treatment, supported employment, cognitive remediation and social skills training according to need. ^[2][3]
• Supported employment programmes when the person wishes to work. ^[2]

Relapse is common and predictable. A first episode that is treated early and continued for an adequate period has a much better course.

Medication duration. Inform the person that stopping medication carries a high risk of relapse within 1 to 2 years. ^[2] Guidelines and reviews commonly recommend continuing antipsychotic treatment for at least 1 to 2 years after remission following a first episode, and long-term or effectively indefinite maintenance after recurrent episodes. ^[6] If antipsychotics are withdrawn, do it gradually, monitor closely and continue to monitor for at least 2 years. ^[2] More than half of patients who stop abruptly relapse within a year. ^[6]

Intermittent dosing (drugs only during early relapse signs) is not used routinely; reserve it for people unwilling to accept continuous treatment or with side-effect sensitivity. ^[2]

Early warning signs. Most relapses are preceded by a prodrome: insomnia, anxiety, low mood, social withdrawal, suspiciousness. A written relapse prevention plan (triggers, early signs, who to contact, and access to crisis services) is part of good care. ^[2]

Health and lifestyle. People with psychosis or schizophrenia, especially on antipsychotics, should be offered a combined healthy-eating and physical-activity programme; smokers should be offered help to stop (avoid bupropion; take care with QT and interactions when using varenicline or bupropion). Monitor weight, cardiovascular and metabolic indicators routinely; comply via board-level performance indicators. ^[2]

• Any new or suspected psychosis should be referred to secondary or early intervention services without delay. ^[2]
• Refer urgently for inpatient or crisis assessment when there is acute risk, severe self-neglect, or catatonia. ^[2]
• For non-response to two adequate trials, refer for clozapine assessment and specialist medicines authorisation. ^[2]
• Refer to general medical care for suspected myocarditis, neutropenia or new cardiac or metabolic symptoms on antipsychotics. ^[2][6]

• Relapse and rehospitalisation, especially within the first 2 years.
• Treatment resistance in 20 to 30% of patients (inadequate response after adequate trials of two antipsychotics). ^[9]
• Metabolic syndrome (weight gain, dyslipidaemia, diabetes): particularly with olanzapine and clozapine. ^[5]
• Extrapyramidal symptoms (acute dystonia, parkinsonism, akathisia) and, in the long term, tardive dyskinesia. ^[2][5]
• Hyperprolactinaemia with galactorrhoea and sexual dysfunction, especially with risperidone and paliperidone. ^[2]
• Cardiovascular death (the largest contributor to the 9-year mortality gap), including QT-related arrhythmia with high-dose or QT-prolonging drugs.
• Suicide and self-harm.
• Substance use disorders, which worsen prognosis and complicate adherence.
• Neuroleptic malignant syndrome, rare but life-threatening (fever, rigidity, autonomic instability). Stop the offending drug immediately and provide supportive care. ^[7]
• Catatonia and its complications (aspiration pneumonia, thromboembolism, contractures, malnutrition). ^[7]
• Social disability: isolation, unemployment, homelessness, and victimisation; stigmatisation.

Prognosis is heterogeneous. With modern treatment, one third or more of patients achieve complete remission. ^[1] Roughly a third have persistent difficulties despite treatment, and a third remit and relapse in a variable pattern. Negative and cognitive symptoms are the main long-term drivers of disability. ^[6]

Factors associated with a better outcome include: female sex, later onset, good premorbid functioning and education, short duration of untreated psychosis, acute onset with positive symptoms, good insight and adherence, and strong social support. Worse outcomes are associated with early onset, insidious onset, prominent negative symptoms, substance use, and poor adherence. ^[5][6]

Early, adequate and continued treatment changes prognosis: much of the apparent progressive course of the 20th century reflected the long untreated periods of the illness. ^[6]

There is no proven universal prevention, because the large majority of at-risk individuals never develop schizophrenia. However, specific strategies help:

• Identify people at clinical high risk (attenuated symptoms, transient symptoms, or first-degree relatives with psychosis) and offer individual CBT, with or without family intervention, plus treatment of comorbid anxiety, depression or substance misuse. Do not offer antipsychotic medication to prevent psychosis. ^[2]
• Shorten duration of untreated psychosis: any first psychotic symptoms should be recognised and referred promptly; easier access to early intervention services is the main modifiable factor. ^[2]
• Screening is not recommended in the general population; the tool is a low threshold for referral. ^[2]
• Physical health is the main preventable cause of the mortality gap; screen and treat cardiovascular risk factors from the start. ^[1][2]
• Avoidance of high-potency cannabis in adolescence is a reasonable public-health message; heavy use is associated with elevated risk. ^[1]

Children and adolescents. Childhood-onset schizophrenia is rare. Antipsychotics are used in lower doses with careful monitoring; clozapine is reserved for treatment resistance. Catatonia in adolescence follows the same treatment principles as in adults. ^[6][7]

Older adults. Minimise anticholinergic and metabolic burden; high antipsychotic doses are associated with increased mortality. Clozapine and olanzapine are associated with marked metabolic side effects and are generally avoided unless clearly indicated. ^[6]

Pregnancy. Use the lowest effective dose and make decisions with the woman and her obstetric team. First-generation agents (especially haloperidol) have the longest safety data, and olanzapine has not been consistently associated with increased major congenital malformations in observational studies. Treat severe illness rather than stop medication abruptly; relapse, not the drug, is usually the greater risk to mother and baby. ^[6]

People with comorbid substance use. Partial dopamine agonists (aripiprazole, cariprazine) have shown good control of psychosis and favourable tolerability in schizophrenia with comorbid substance use disorders. ^[6]

People with neurodevelopmental conditions. Schizophrenia is only diagnosed in autism or communication disorders if prominent delusions or hallucinations persist for at least 1 month; assessment and treatment should be adapted and multidisciplinary. ^[5]

• Non-specialist clinicians can recognise and manage psychosis with the WHO mhGAP algorithms: assess, ensure safety, and start a low-dose antipsychotic with follow-up, referring when possible. ^[4]
• A single low-cost antipsychotic (often haloperidol or chlorpromazine, or a low-cost second-generation agent where available) plus structured psychosocial care is the practical minimum.
• ECG, metabolic testing and haematological monitoring may be unavailable; use clinical monitoring, the lowest effective dose, and urgent referral for suspected agranulocytosis or cardiac symptoms. ^[2][6]
• Community-based psychosocial rehabilitation and family involvement matter as much in low-resource settings as elsewhere. ^[1][4]

• Schizophrenia is diagnosed when at least two core symptoms persist for a significant part of 1 month, within a 6-month or longer disturbance, with functional decline.
• The related disorders are separated mainly by duration: under 1 month (brief psychotic), 1 to under 6 months (schizophreniform), concurrent mood episode (schizoaffective), delusions alone for at least 1 month (delusional).
• Positive symptoms arise from mesolimbic dopamine overactivity; negative and cognitive symptoms from mesocortical underactivity and structural change.
• No laboratory test diagnoses schizophrenia: diagnosis is clinical, after excluding medical, substance and mood causes.
• First-episode care combines a low-dose antipsychotic with family intervention and CBT, inside an early intervention or coordinated specialty care programme.
• All antipsychotics are broadly similar in efficacy except clozapine; choice rests on which side effects and cautions fit the patient.
• Use one drug at a time, titrate slowly, and judge efficacy after 4 to 6 weeks; do not rapidly escalate or combine long term.
• Monitor baseline and treatment-emergent cardiometabolic and prolactin effects on the NICE schedule: weight weekly for 6 weeks, then at 12 weeks, 1 year and annually; waist annually; pulse and BP at 12 weeks, 1 year and annually; glucose or HbA1c and lipids at 12 weeks, 1 year and annually.
• Clozapine is reserved for treatment-resistant illness after at least two adequate trials; titrate from 12.5 mg to 300–600 mg and enforce haematological monitoring.
• Catatonia is treated first with benzodiazepines (lorazepam), with ECT when response is inadequate or the picture is life-threatening; stop antipsychotics acutely.
• Continue antipsychotics for at least 1 to 2 years after a first episode; withdraw only slowly and monitor for 2 years.
• The mortality gap is mainly medical: treat cardiovascular and metabolic risk and smoking from the outset.

First-episode psychosis; bipolar disorder and unipolar psychotic depression; delirium; dementia; substance-induced psychosis; neuroleptic malignant syndrome; tardive dyskinesia; catatonia; autism-spectrum disorder; anti-NMDA receptor encephalitis. Plain text only; links will be added as those topics are verified.