Schizophrenia

For the treatment of clozapine induced constipation, please see the Constipation recommendations in the Gastro-intestinal chapter of the formulary.

SIGN 131: Schizophrenia BAP Consensus Guidelines NICE CG178: Psychosis and Schizophrenia in adults Maudsley Prescribing Guidelines in Psychiatry

Initial choice of an antipsychotic will be dependent on individual requirements. If a depot is likely to be required in the future, consideration should be given to selecting an oral antipsychotic that is also available in depot formulation.

1-4mg daily as single dose or in divided doses. Move to alternative agent if dose reaches 4mg and no response.

10mg daily adjusted to usual range of 5-20mg daily; doses greater than 10mg daily only after reassessment; maximum 20mg daily.

Acute psychotic episode in schizophrenia 400-800mg daily in 2 divided doses, maximum 1.2g per day. Schizophrenia with predominantly negative symptoms, 50-300mg daily.

Initially 250micrograms twice daily, then increased in steps of 250micrograms twice a day on alternate days, adjusted according to response; usual dose 500micrograms twice daily (max per dose 1mg twice daily).

10-15mg once daily; usual dose 15mg once daily; max. per dose 30mg once daily.

300mg once daily for day 1, then 600mg once daily for day 2, then, adjust according to response. Maximum 800mg per day.

1.5mg once daily, increased in steps of 1.5mg if required; maximum 6mg per day.

Initially 25mg 3 times a day, adjusted according to response, dose to be taken at night; maintenance 75mg-300mg daily, increased up to 1g daily.

Initially 37mg once daily, increased up to 148mg once daily.
Initially 18.5mg dose when given with moderate CYP3A4 inhibitors, max. 74mg once daily.

Prescribing Notes:

Antipsychotics should be initiated with caution in the first episode (i.e. start with low dose) and monitored carefully due to the risk of adverse effects, particularly haloperidol.
The usual dose of haloperidol in first episode schizophrenia is 2-4mg daily. A lower dose of haloperidol may be effective and well tolerated in first episode psychosis. Initial doses should be maintained for a sufficient period of time to allow for the medication to take full effect.
Quetiapine, risperidone and aripiprazole are other antipsychotics that may be preferable due to differing side effect profiles.
It is recommended that baseline physical health checks are carried out before prescribing antipsychotics, followed by regular physical health monitoring.
Patients should remain on the antipsychotic which controlled their symptoms unless symptoms return or side-effects are intolerable; the dose should be monitored and reviewed regularly with specialist advice.
Medicines monitoring should be undertaken as per local protocols.
Specialist advice should be sought before discontinuing antipsychotics due to the risk of relapse.
In general, due to its side-effect profile chlorpromazine should not be initiated in the elderly. Chlorpromazine also has a high risk of photosensitivity.
Haloperidol has a high risk of extrapyramidal side effects, especially in the elderly. The manufacturer of haloperidol recommends a baseline ECG before starting haloperidol and at regular intervals during treatment due to risk of QT prolongation /ventricular arrhythmias.
All antipsychotics can cause weight gain and can increase the risk of diabetes, see ‘Treatment of antipsychotic associated weight gain’ pathway for advice.
Antipsychotics should be deprescribed if there is no clinical benefit in older patients. Guidance can be found from local specialists, Polypharmacy Guidance and Deprescribing antipsychotics: a guide for clinicians.
General notes on prescribing in pregnancy are available in the Pregnancy section of the formulary.

History Notes

09/04/2024

Addition of link to general notes on prescribing in pregnancy, ERWG May 24.

27/10/2022

East Region Formulary content agreed.

When switching from oral to depot antipsychotic medication please consult local guidelines, specialists and/or Maudsley Prescribing Guidelines in Psychiatry for equivalent doses.
Extra care should be taken when prescribing depot injections to ensure correct salt formulation is selected.

By deep intramuscular injection into gluteal muscle: test dose 20mg then after at least 7 days 20-40mg every 2-4 weeks, adjusted to response; max 400mg weekly; usual maintenance dose 50mg every 4 weeks to 300mg every 2 weeks.

By deep intramuscular injection into gluteal muscle: test dose 100mg, followed after at least 7 days by 200-500mg or more, repeated at intervals of 1-4 weeks, adjusted according to response; max 600mg weekly.

By deep intramuscular injection into deltoid muscle: 150mg on day 1, then 100mg on day 8, then adjusted at monthly intervals according to response; recommended maintenance dose 75mg (range 25-150mg) monthly.

By deep intramuscular injection, into the deltoid or gluteal muscle, initially 175–525 mg every 3 months, adjusted according to response, dose is based on previous once-monthly intramuscular paliperidone and should be initiated in place of the next scheduled dose - consult product literature.

Consult product literature.

By deep intramuscular injection into gluteal muscle: 400mg every month.

By deep intramuscular injection into gluteal muscle: 25mg-150mg every 4 weeks, adjusted in steps of up to 50mg every 4 weeks if required; recommended maintenance 50-200mg every 4 weeks.

Prescribing Notes:

Depot injections should be initiated on specialist advice, taking into account patient preference on formulation or where depot injections may reduce adherence difficulties. They may produce more extrapyramidal reactions than oral preparations.
For the majority prescribing of injectable antipsychotics will remain in specialist services.
For flupentixol decanoate and zuclopenthixol decanoate, it is recommended that a test dose of the depot injection should be given first since some side-effects are prolonged. Plasma levels of these antipsychotics released from depot accumulate during the first few months of therapy without increasing the given dose; steady state is only achieved after 6-8 weeks.
For patients who have never taken aripiprazole, tolerability with oral aripiprazole must occur prior to initiating treatment with aripiprazole depot.
Paliperidone depot is indicated for maintenance treatment of schizophrenia in patients who are stabilized with or have had previous responsiveness to oral paliperidone or risperidone. Paliperidone can be considered as an alternative in patients where the use of a monthly/3 monthly/6 monthly depot would be advantageous.
Individual responses to antipsychotic depot injections are variable; treatment should be selected and titrated according to the patient’s response. There is no evidence that any one depot antipsychotic is particularly suitable for a specific patient group.
First-generation antipsychotic depot injections are administered at intervals of 1-4 weeks dependent on patient requirements and drug half-life.
Extrapyramidal reactions occur less frequently with second generation antipsychotic depot preparations.
General notes on prescribing in pregnancy are available in the Pregnancy section of the formulary.

History Notes

09/04/2024

Addition of link to general notes on prescribing in pregnancy, ERWG May 24.

09/10/2023

Update to paliperidone formulations, ERFC June 23.

27/10/2022

East Region Formulary content agreed.

View all

Schizophrenia, adult over 18 years, 12.5mg once or twice daily (elderly 12.5mg once) on first day then 25-50mg (elderly 25-37.5mg) on second day then increased gradually (if well tolerated) in steps of 25-50mg daily (elderly max. increment 25mg daily) over 14-21 days up to 300mg daily in divided doses (larger dose at night, up to 200mg daily may be taken as a single dose at bedtime); if necessary may be further increased in steps of 50-100mg once (preferably) or twice weekly; usual dose 200-450mg daily (max. 900mg daily).
Note: Restarting after interval of more than 2 days, 12.5mg once or twice on first day (but may be feasible to increase more quickly than on initiation) – extreme caution if previous respiratory or cardiac arrest with initial dosing.

Prescribing Notes:

Clozapine should be initiated and maintained by specialists and supplied as per Board agreements. Patients must be registered with the Clozaril Patient Monitoring Service. Clozapine can cause serious side-effects such as agranulocytosis, seizures, cardiomyopathy and myocarditis. Gastro-intestinal obstruction and paralytic ileus may also occur.
It is vital that constipation is recognized early and actively treated. Consider prescribing regular laxatives to patients at risk of gastrointestinal side effects, see ‘Treatment of clozapine induced constipation’ pathway.
If a patient presents with signs of fever or infection then an urgent full blood count should be undertaken.
Patients who have not taken clozapine for 48 hours will require re-titration. Seek specialist advice.
Clozapine has been associated with varying degrees of impairment of intestinal peristalsis; this effect can range from constipation, which is very common, to very rare intestinal obstruction, faecal impaction, and paralytic ileus. Exercise particular care in patients receiving other drugs known to cause constipation (especially those with anticholinergic properties), patients with a history of colonic disease or lower abdominal surgery, and in patients aged 60 years and older. Clozapine is contraindicated in patients with paralytic ileus. Advise patients to report constipation immediately and actively treat any constipation that occurs (MHRA October 2017).
See local Board protocols for clozapine, such as Lothian Clozapine Handbook (intranet).
Changes in smoking habit can significantly affect clozapine plasma levels increasing the risk of relapse (on starting or increasing smoking) or toxicity (on stopping or reducing smoking).
General notes on prescribing in pregnancy are available in the Pregnancy section of the formulary.

History Notes

09/04/2024

Addition of link to general notes on prescribing in pregnancy, ERWG May 24.

27/10/2022

East Region Formulary content agreed.

As per specialist.

History Notes

27/10/2022

East Region Formulary content agreed.

Lifestyle interventions (incorporating physical activity, dietary change and behavioural components) are considered first line for the management of antipsychotic associated weight gain.

500mg once daily, slowly increasing by intervals of at least one week (preferably longer, over two to three weeks) to a usual maximum of 2g/daily as tolerated in divided doses.

Prescribing Notes:

If there is evidence of weight gain despite non-pharmacological measures, if clinically appropriate consider switching to an alternative antipsychotic with less potential to produce weight gain.
If these measures are unsuccessful consider metformin to treat antipsychotic associated weight gain.
Avoid metformin if there is current alcohol misuse or dependence due to increased risk of hypoglycaemia or lactic acidosis.
Consider metformin to prevent antipsychotic weight gain when antipsychotics initiated if BMI >25kg/m² and unable to comply with lifestyle interventions.
‘Sick day guidance’ for metformin applies. Provide advice to stop taking metformin during periods of intercurrent illness (i.e. when unwell with vomiting and/or diarrhoea or if unable to eat or drink).
Treatment with metformin is initiated by or on the advice of a specialist and may be continued in primary care with routine monitoring. Ongoing treatment to be reviewed if the antipsychotic is stopped/changed or weight is regained.

History Notes

27/10/2022

East Region Formulary content agreed.

Specialist referral is recommended for the treatment of acute psychoses in children and adolescents. Initial choice of an antipsychotic will be dependent on individual requirements. If a depot is likely to be required in the future, consideration should be given to selecting an oral antipsychotic that is also available in depot formulation.

Dose as per specialist and BNFc.

Prescribing Notes:

Antipsychotics should be initiated with caution in the first episode (i.e. start with low dose) and monitored carefully due to the risk of adverse effects, particularly haloperidol.
Quetiapine, risperidone and aripiprazole are other antipsychotics that may be preferable due to differing side effect profiles.
Aripiprazole is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years and older.
Lurasidone is indicated for the treatment of schizophrenia in adults and adolescent aged 13 years and over.
Amisulpride is contraindicated in children before the onset of puberty.
Since extrapyramidal side-effects occur more frequently in children and adolescents, atypical antipsychotics, which have a reduced incidence, are preferred.
It is recommended that baseline physical health checks are carried out before prescribing antipsychotics, followed by regular physical health monitoring.
Patients should remain on the antipsychotic which controlled their symptoms unless symptoms return or side-effects are intolerable; the dose should be monitored and reviewed regularly with specialist advice.
Medicines monitoring should be undertaken as per local protocols.
Specialist advice should be sought before discontinuing antipsychotics due to the risk of relapse.
All antipsychotics can cause weight gain and can increase the risk of diabetes, see ‘Treatment of antipsychotic associated weight gain’ pathway for advice.
Antipsychotics should be deprescribed if there is no clinical benefit in patients. Guidance can be found from local specialists, Polypharmacy Guidance and Deprescribing antipsychotics: a guide for clinicians.

Clozapine

Clozapine is indicated in treatment-resistant schizophrenic patients and in schizophrenia patients who have severe, untreatable neurological adverse reactions to other antipsychotic agents, including atypical antipsychotics.
The safety and efficacy of clozapine in children and adolescents under the age of 16 years have not yet been established.
Clozapine should be initiated and maintained by specialists and supplied as per Board agreements. Patients must be registered with the relevant monitoring service.
Clozapine can cause serious side-effects such as agranulocytosis, seizures, cardiomyopathy and myocarditis. Gastro-intestinal obstruction and paralytic ileus may also occur.
It is vital that constipation is recognized early and actively treated. Consider prescribing regular laxatives to patients at risk of gastrointestinal side effects, see ‘Treatment of clozapine induced constipation’ pathway.
If a patient presents with signs of fever or infection then an urgent full blood count should be undertaken.
Patients who have not taken clozapine for 48 hours will require re-titration. Seek specialist advice.
Clozapine has been associated with varying degrees of impairment of intestinal peristalsis; this effect can range from constipation, which is very common, to very rare intestinal obstruction, faecal impaction, and paralytic ileus. Exercise particular care in patients receiving other drugs known to cause constipation (especially those with anticholinergic properties), patients with a history of colonic disease or lower abdominal surgery, and in patients aged 60 years and older. Clozapine is contraindicated in patients with paralytic ileus. Advise patients to report constipation immediately and actively treat any constipation that occurs (MHRA October 2017).
See local Board protocols for clozapine, such as Lothian Clozapine Handbook (NHS Lothian intranet).
Denzapine brand is the licensed version of clozapine 50mg/ml suspension.

History Notes

15/01/2024

East Region Formulary content agreed.

There is limited information on the use of depot injections in adolescents. They are not recommended in children under 12 years of age. When switching from oral to depot antipsychotic medication please consult local guidelines, specialists and/or Maudsley Prescribing Guidelines in Psychiatry for equivalent doses.
Extra care should be taken when prescribing depot injections to ensure correct salt formulation is selected.

Dose as per specialist and BNFc.

Prescribing Notes:

Depot injections should be initiated on specialist advice, taking into account patient preference on formulation or where depot injections may reduce adherence difficulties. They may produce more extrapyramidal reactions than oral preparations.
The BNF recommends that a test dose of the depot injection should be given first since some side-effects are prolonged.
For patients who have never taken aripiprazole, tolerability with oral aripiprazole must occur prior to initiating treatment with aripiprazole depot.
Paliperidone depot is indicated for maintenance treatment of schizophrenia in patients who are stabilized with or have had previous responsiveness to oral paliperidone or risperidone. Paliperidone can be considered as an alternative in patients where the use of a monthly/3 monthly depot would be advantageous.
Individual responses to antipsychotic depot injections are variable; treatment should be selected and titrated according to the patient’s response. There is no evidence that any one depot antipsychotic is particularly suitable for a specific patient group.
Extrapyramidal reactions occur less frequently with second generation antipsychotic depot preparations.

History Notes

15/01/2024

East Region Formulary content agreed.

Lifestyle interventions (incorporating physical activity, dietary change and behavioural components) are considered first line for the management of antipsychotic associated weight gain.

Dose as per specialist.

Prescribing Notes:

If there is evidence of weight gain despite non-pharmacological measures, if clinically appropriate consider switching to an alternative antipsychotic with less potential to produce weight gain.
If these measures are unsuccessful consider metformin to treat antipsychotic associated weight gain.
Consider metformin to prevent antipsychotic weight gain when antipsychotics initiated if BMI >25kg/m² and unable to comply with lifestyle interventions.
‘Sick day guidance’ for metformin applies. Provide advice to stop taking metformin during periods of intercurrent illness (i.e. when unwell with vomiting and/or diarrhoea or if unable to eat or drink).
Treatment with metformin is initiated by or on the advice of a specialist and may be continued in primary care with routine monitoring. Ongoing treatment to be reviewed if the antipsychotic is stopped/changed or weight is regained.

History Notes

15/01/2024

East Region Formulary content agreed.