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Psychosis and Schizophrenia

NICE clinical guideline [CG178] Psychosis and schizophrenia in adults: prevention and management. Last updated: Mar 2014. NICE CKS Psychosis and schizophrenia. Last revised: May 2025.

Guidelines

This section applies to those that have NOT yet developed first episode of psychosis but at increased risk of developing psychosis (i.e. those not yet meet criteria for psychosis).
 

Referral is indicated if (factors that put a person at increased risk of developing psychosis)
  • Patient is distressed with decline in social functioning, and
  • Any of the following
    • Transient or attenuated psychotic symptoms
    • Psychosis suggestive behaviour / experiences
    • 1st degree relative with psychosis or schizophrenia

Treatment options for those at increased risk of psychosis (see above):
  • Offer CBTCognitive behavioural therapy +/- family intervention
  • Treat associated mental health disorders accordingly (e.g. depression, anxiety disorders, personality disorder)

Dot NOT offer antipsychotic medications in those only at increased risk of developing psychosis to decrease the risk of prevent it from happening.

Do not start antipsychotic medications in primary care (unless done in consultation with consultant psychiatrist)

Refer to secondary care for assessment, then offer:
  • Oral antipsychotic medication, and
  • Psychological intervention 
    • Individual CBTCognitive behavioural therapy
    • Family intervention
 

Antipsychotic depot injections (given every 1-4 weeks) are used for maintenance therapy when adherence to oral treatment is unreliable.

Structural neuroimaging are not recommended as routine initial investigations for first-episode psychosis

NICE recommends choosing antipsychotic medications based on side effect profile 
  • NICE could not make a recommendation for a preference of one antipsychotic over another due to their similar efficiacy

Note that clozapine is generally offered to those who failed to respond to 2 different antipsychotics
  • Clozapine is generally offered to people who do not respond adequately to two other antipsychotics and is always initiated and monitored in secondary care.
 

Generally, 2nd generation (atypical) antipsychotics are preferred due to the lower risk of extrapyramidal side effects.

Secondary care team should monitor the patient for at least 12 months or until the patient is stabilised before transferring back to primary care.
 

Clinical assessment

  • Weight and waist circumference
  • Pulse and blood pressure
  • Assess for movement disorders, nutritional status, diet and level of physical activity

Blood tests
  • Fasting blood glucose / HbA1c
  • Lipid levels
  • Prolactin level

Baseline ECG is not routinely needed, but indicated in
  • Specified in summary of product characteristics (notable ones include haloperidol and amisulpride)
  • High cardiovascular risk (e.g. hypertension)
  • Personal history of cardiovascular disease
  • Patient is being admitted as inpatient

Ask and assess for:

  • Response to treatment
  • Side effects of treatment
  • Emergence of movement disorders (esp. if taking 1st generation antipsychotics)
  • Adherence

Investigations:
  • Weight: weekly for first 6 weeks → at 12 weeks → at 1 year → yearly
  • Waist circumference: yearly
  • Pulse and blood pressure: at 12 weeks → at 1 year → yearly
  • Fasting blood glucose or HbA1c, lipid levels: at 12 weeks → at 1 year → yearly

MoA: potent D2 receptor antagonist (particularly in mesolimbic pathway)

Examples:
  • Haloperidol
  • Chlorpromazine
  • Flupentixol

Main side effect profile:
  • Extrapyramidal side effects (dystonia, parkinsonism, akathisia, tardive dyskinesia)
  • Hyperprolactinaemia
  • Sedation

MoA: (notable with less D2 antagonism and more additional receptor activity thus the side effect profile)
  • D2 receptor antagonist
  • 5-HT2A antagonist
  • Histamine, adrenergic, muscarinic receptors antagonist

Examples:
  • Risperidone
  • Olanzapine
  • Quetiapine
  • Aripiprazole (notable with pre-synpatic D2 agonist property)
  • Clozapine

Main side effect profile:
  • Risk of extrapyramidal side effects and hyperprolactinaemia is less than 1st generation
  • Metabolic syndrome risk is higher than 1st generation
  • Antimuscarinic effects
  • Risk of stroke (esp. in elderly with dementia)
  • Risk of VTE (esp. in elderly)

Side effect Main at risk drugs
QTc prolongation
  • Haloperidol (1st gen)
  • Quetiapine, amisulpride (2nd gen)
Hyperprolactinaemia
  • All 1st gen (due to strong D2 antagonism)
  • Certain 2nd gen is at higher risk (but not all, like 1st gen)
    • Risperidone
    • Amisulpride
Metabolic syndrome Mainly a problem of 2nd gen, but espeically in:
  • Olanzapine
  • Quetiapine
  • Clozapine

Aripiprazole specific side effects:
  • Generally lower risk of metabolic syndrome and sedation compared with other atypicals
  • Associated with rare but well-documented cases of impulse control disorders (e.g. pathological gambling, compulsive shopping, hypersexuality) (thought to be associated with the partial dopamine agonist activity)

Clozapine specific side effects:
  • Hypersalivation
  • Constipation (can lead to ileus or bowel obstruction)
  • Seizure threshold reduction
  • Myocarditis
  • Agranulocytosis (serious but rare, ~1%)

References

Author: Adams Lau
Reviewer:
Last edited: 24/07/25