Guidelines

Prevention of Psychosis

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

Referral Criteria

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

Prevention

Treatment options for those at increased risk of psychosis (see above):

• Offer CBT +/- family intervention
• Treat associated mental health disorders accordingly (e.g. depression, anxiety disorders, personality disorders)

Do NOT offer antipsychotic medications to those who are only at increased risk of developing psychosis to prevent it from happening.

Management

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

Refer to secondary care for assessment, then offer:

• Oral antipsychotic medication, and
• Psychological intervention
  • Individual CBT
  • Family intervention

Antipsychotics

Choice of Antipsychotics

NICE recommends choosing antipsychotic medications based on the side effect profile

• NICE could not make a recommendation for a preference of one antipsychotic over another due to their similar efficacy (apart from clozapine)

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.

Monitoring of Antipsychotics

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

Baseline Investigations

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

Ongoing Monitoring

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

Antipsychotics Pharmacology

1st Generation (Typical) Antipsychotics

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

Examples:

• Haloperidol
• Chlorpromazine
• Flupentixol

Main side effect profile:

• Extrapyramidal side effects
  • Parkinsonian symptoms (including bradykinesia, rigidity and tremor) – more common in elderly females or those with pre-existing neurological damage (e.g. stroke)
  • Acute dystonia (uncontrolled muscle spasm) – more common young males and can appear within hours of starting the drug
  • Akathisia (restlessness) – characteristically occurs within hours to weeks of starting antipsychotic treatment or on dose increase and may be mistaken for psychotic agitation
  • Tardive dyskinesia (abnormal involuntary movements of lips, tongue, face, and jaw) – typically develop following long-term or high-dose therapy (irreversible in some patients, even after treatment discontinuation)
• Hyperprolactinaemia
• Sedation

2nd Generation (Atypical) Antipsychotics

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 receptor antagonist

Examples:

• Risperidone
• Olanzapine
• Quetiapine
• Aripiprazole (notable with presynaptic D2 agonist property)
• Clozapine

Main side effect profile:

• Lower risk of extrapyramidal side effects and hyperprolactinaemia compared to 1st generation
• Metabolic syndrome risk is higher than 1st generation
• Antimuscarinic effects
• Postural hypotension (due to adrenergic receptor antagonism)
• Risk of stroke (esp. in elderly with dementia)
• Risk of VTE (esp. in elderly)

High-Yield Side Effects

Aripiprazole specific drug profile:

• 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)

There is a high risk of relapse if an antipsychotic is stopped after 1–2 years

• DO NOT stop antipsychotics abruptly – stop gradually and monitor closely to avoid the risk of acute withdrawal syndromes or rapid relapse
• Patients should be monitored for 2 years after withdrawal of antipsychotic medication for signs and symptoms of relapse

Clozapine-Specific Information

Clozapine specific side effects (in addition to those mentioned above):

• Hypersalivation
• Constipation (potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus) – thus important not to co-prescribe with anti-motility drugs (e.g. loperamide, opioids)
• Myocarditis (most commonly in first 2 months)
• Agranulocytosis (serious but rare, ~1%)
• Seizure threshold reduction
• Smoking interacts with blood clozapine concentration (both stopping and starting smoking)
  • Patients who smoke / started smoking will have lower blood clozapine levels (cigarette smoke induces CYP1A2 → increases clozapine metabolism → lowers clozapine levels)
  • Patients who stops smoking will have higher blood clozapine levels (risk of toxicity)

Additional monitoring for clozapine (in addition to those mentioned above):

• Regular FBCs (specifically, leukocyte and differential blood counts – to check for neutropaenia)
  • Frequency: weekly for 18 weeks, then fortnightly for up to 1 year, then monthly as part of clozapine patient monitoring service
  • If absolute neutrophil count falls <1.5 x10⁹/L (typical lower reference range) OR leukocyte count <3 x10⁹/L → discontinue permanently and refer to haematologist
• Monitoring blood clozapine concentration is necessary if:
  • Patient stops smoking or switches to an e-cigarette
  • Concomitant medicines may interact to increase blood clozapine levels
  • Patient has pneumonia or other serious infection
  • Reduced clozapine metabolism is suspected
  • Toxicity is suspected

Starting clozapine therapy:

• Always start low, and titrate up slowly (12.5 mg 1–2 times a day for day 1, then 25–50 mg for day 2, then increased, if tolerated, in steps of 25–50 mg daily, dose to be increased gradually over 14–21 days, increased to up to 300 mg daily in divided doses)
• If clozapine dose has been missed for >48 hours → re-introduce clozapine again from 12.5 mg a day and titrate upwards

References