MHRA Drug Safety Update (August 2020): Clozapine and other antipsychotics - monitoring blood concentrations for toxicity:

• Please see the clozapine entry below for the clozapine protocol which defines the circumstances in which monitoring of plasma clozapine levels is appropriate
• For antipsychotics other than clozapine, drug level monitoring for toxicity is not routine practice. This service is not provided by local trust laboratories. Local advice is that clinicians who have concerns about a patient receiving an antipsychotic should in the first instance contact the mental health specialist team for advice. This applies to patients with symptoms suggestive of toxicity, or when concomitant medicines may interact to increase antipsychotic drug levels, and also when non-adherence or poor response to treatment is suspected.

Antipsychotics (first-generation)

Chlorpromazine

• Tablets 25mg, 50mg, 100mg (£41.44 = 100mg daily)
• Oral solution 25mg in 5ml, 100mg in 5ml (£5.50 = 150ml x 100mg in 5ml)

Indications

• Schizophrenia and other psychoses, mania, short-term adjunctive management of severe anxiety, psychomotor agitation, excitement, and violent or dangerously impulsive behaviour

Haloperidol

• Tablets 1.5mg, 5mg, 10mg (£16.02 = 10mg daily)
• Oral solution sugar free 5mg in 5ml, 10mg in 5ml (£7.31 = 100ml x 5mg in 5ml)
• Solution for injection ampoules 5mg in 1ml (£6.13 = ampoule)

Indications

• Schizophrenia and other psychoses
• Agitation and restlessness in the elderly
• Short-term adjunctive management of severe anxiety
• Motor tics, adjunctive treatment in choreas and Tourette syndrome
• Nausea and vomiting, see Prescribing in Palliative Care, I/M injection, 1–2mg
• Haldol, maintenance in schizophrenia and other psychoses

Notes

1. Baseline ECG is recommended prior to treatment with haloperidol in all patients, especially in the elderly and patients with a positive personal or family history of cardiac disease or abnormal findings on cardiac clinical examination
2. MHRA Drug Safety Update (December 2021): Haloperidol (Haldol): reminder of risks when used in elderly patients for the acute treatment of delirium
   1. special caution is required when using haloperidol for the acute treatment of delirium in frail, elderly patients
   2. only consider haloperidol for delirium when non-pharmacological interventions are ineffective and no contraindications are present (including Parkinson's disease and dementia with Lewy bodies)
   3. before initiating treatment, a baseline electrocardiogram (ECG) and correction of any electrolyte disturbances is recommended; cardiac and electrolyte monitoring should be repeated during treatment (see safety update)
   4. prescribe the lowest possible dose for the shortest possible time, ensuring that any dose up-titration is gradual and reviewed frequently
   5. monitor for and investigate early any extrapyramidal adverse effects, such as acute dystonia, parkinsonism, tardive dyskinesia, akathisia, hypersalivation, and dysphagia

Levomepromazine

• Tablets 25mg (£20.26 = 84 tablets)
• Solution for injection ampoules 25mg in 1ml (£2.01 = ampoule)
• Tablets 6mg

Indications

• Palliative care guidance

Sulpiride

• Tablets 200mg, 400mg (£22.50 = 30 x 400mg)
• Oral solution sugar free 200mg in 5ml (£93.64 = 150ml)

Indications

• Schizophrenia

Trifluoperazine

• Tablets 1mg, 5mg (£59.12 = 112 x 1mg)
• Oral solution sugar free 1mg in 5ml, 5mg in 5ml (£56.19 = 150ml x 5mg in 5ml)

Indications

• Schizophrenia and other psychoses, short-term adjunctive management of psychomotor agitation, excitement, and violent or dangerously impulsive behaviour

Notes

1. Trifluoperazine is included in the formulary for currently treated patients, there should be no new initiations

Zuclopenthixol dihydrochloride

• Tablets 2mg, 10mg, 25mg (£8.06 = 100 x 10mg)

Indications

• Schizophrenia and other psychoses

Antipsychotics (second-generation)

Amisulpride

• Tablets 50mg, 100mg, 200mg, 400mg (£33.62 = 400mg daily)
• Oral solution sugar free 100mg in 1ml (£109.57 = 60ml)

Indications

• Schizophrenia

Aripiprazole

• Tablets 5mg, 10mg, 15mg, 30mg (£6.30 = 15mg daily)
• Orodispersible tablet 10mg, 15mg (£72.91 = 15mg daily)
• Oral solution 1mg in 1ml (£94.67 = 150ml)
• Injection 7.5mg/ml, 1.3ml = 9.75mg vial

Indications

• Schizophrenia
• Treatment and recurrence prevention of mania

Notes

1. NICE TA213 Aripiprazole for schizophrenia in people aged 15 to 17 years (Jan 2011)
2. NICE TA292 Aripiprazole for moderate to severe manic episodes in adolescents with bipolar I disorder (July 2013)
3. Short acting injection should be used only in secondary care in accordance with Trust's rapid tranquillisation policy. 
4. MHRA Drug Safety Update (December 2023): Aripiprazole (Abilify and generic brands): risk of pathological gambling
   1. Yellow Card reports of gambling disorder and pathological gambling associated with aripiprazole use have increased in number. The reports occurred in patients with and without a prior history of gambling disorder and the majority were reported to resolve upon reduction of dose or stopping treatment with aripiprazole. 
   2. Advise patients and their caregivers to be alert to the development of new or increased urges to gamble and other impulse control symptoms, such as excessive eating or spending, or an abnormally high sex drive.
   3. Consider dose reduction or stopping the medication if a patient develops these symptoms.
   4. Refer to the safety update for advice for patients, parents and carers

Lurasidone

• Tablets 18.5mg, 37mg, 74mg (£37.60 = 28 x 74mg)

Indications

• Schizophrenia in adults:
  • who have not responded to, or not tolerated, separate trials of amisulpride and aripiprazole.
  • with QTc prolongation (at baseline or during antipsychotic treatment) where patients have previously not responded to, or not tolerated, aripiprazole.
• Schizophrenia in children and adolescents aged 13 years and above who have not responded to, or not tolerated, aripiprazole.

Notes

1. Lurasidone has a higher cost compared to other antipsychotics and no evidence of superior efficacy. However, some evidence suggests it has a lower incidence of antipsychotic associated weight gain; therefore, for the cohort of patients where treatment is routinely commissioned (see notes above), lurasidone may be beneficial for patients with cardiovascular disease and/or diabetes, or for patients who have significant risk factors for developing these conditions (e.g., high Q-RISK score, obesity, pre-diabetic).
2. The routine commissioning of lurasidone is accepted in Devon for the management of schizophrenia in adults only in line with specified criteria (see Commissioning Policy for more details).
3. The routine commissioning of lurasidone is accepted in Devon for the management of schizophrenia in children and adolescents (aged 13 years and above) only in line with specified criteria (see Commissioning Policy for more details).

Olanzapine

• Tablets 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg (£0.92 = 10mg daily)
• Orodispersible tablet 5mg, 10mg, 15mg, 20mg (£49.98 = 10mg daily)
• Injection 10mg/2ml

Indications

• Schizophrenia
• Mania
• Maintenance in schizophrenia – see Schizophrenia and Related Psychoses for specific indications

Notes

1. Olanzapine has been associated with an increased risk of hyperglycaemia, diabetes mellitus and exacerbations of diabetes. In diabetes and in patients with risk factors for diabetes mellitus, appropriate clinical and blood glucose monitoring is conducted.
2. See NICE CG178 Psychosis and schizophrenia in adults.
3. Short acting injection should be used only in secondary care in accordance with Trust's rapid tranquillisation policy
4. Olanzapine long-acting injection is associated with post-injection syndrome. Olanzapine should only be given in health-care facilities where administration of the injection and observation of patients post-injection can be undertaken safely and for at least three hours. The three-hour observation period should be extended as clinically appropriate for patients who exhibit any signs or symptoms consistent with olanzapine overdose. Olanzapine should only be administered by healthcare professionals trained in the appropriate injection technique. Training materials are available at: https://www.zypadhera.co.uk/SignIn.aspx

Quetiapine

• Tablets 25mg, 100mg, 150mg, 200mg, 300mg (£2.51 = 400mg daily)
• Modified-release tablets 50mg, 150mg, 200mg, 300mg, 400mg (click here for preferred brand)

Indications

• Schizophrenia
• Mania, either alone or with mood stabilisers
• Depression in bipolar disorder
• Adjunctive treatment in major depressive disorder

Notes

1. Modified-release quetiapine is only recommended for use when individuals cannot tolerate immediate-release quetiapine or if concordance with a twice daily regimen is difficult.
2. Where a preferred brand is recommended for a particular presentation, prescribing by brand helps ensure cost-efficient use of local NHS resources (see preferred brand link above)

Risperidone

• Tablets 500 micrograms, 1mg, 2mg, 3mg, 4mg, 6mg (£1.66 = 2 x 3mg daily) (£35.54 = 1 x 6mg daily)
• Orodispersible tablet 500 micrograms, 1mg, 2mg, 3mg, 4mg (£87.00 = 2 x 3mg daily)
• Oral solution sugar free 1mg in 1ml (£4.87 = 6mg daily)

Indications

• Acute and chronic psychoses
• Mania
• Short term treatment (up to 6 weeks) of persistent aggression in moderate to severe Alzheimer's dementia unresponsive to non-pharmacological approaches and where there is risk of harm to the patient or others

Notes

1. Due to the cost, orodispersible tablets are included for use in patients where there is suspected non-compliance when compliance can be checked
2. No new patients will receive risperidone long-acting injection. There is an existing cohort of patients who will continue to receive risperidone.
3. Refer to the DPT prescribing guideline PG14: Pharmacological Management of Severe Behavioural & Psychological Symptoms of Dementia (BPSD) for dosing regimen, cautions, treatment review and discontinuation
4. Exercise caution if risperidone is prescribed together with furosemide (higher incidence of mortality observed although mechanism unclear). The risks and benefits of combining risperidone with furosemide or other potent diuretics must be considered prior to use. Refer to risperidone Summary of Product Characteristics for more information.

Clozapine

• Clozaril Tablets 25mg 100mg
• Denzapine suspension 50mg/ml

Indications

• Schizophrenia in patients unresponsive to, or intolerant of, conventional antipsychotic drugs

Notes

1. Prescribers, pharmacies and patients must be registered with either the Clozaril Patient Monitoring Service (CPMS) for those taking tablets or the Denzapine Monitoring Service (DMS) for those taking suspension. Make sure patients are registered in the correct service; they cannot be registered for both. Refer to hospital Pharmacy Department and the:
   1. Livewell Southwest Clozapine policy for mental health staff and Plymouth GP practice staff
   2. DPT policy Pharmacological Treatment of Schizophrenia and Related Psychoses
   3. DPT Clinical Protocol for Clozapine CP19
2. Treatment needs to re-titrated if there has been more than 48 hours between doses. Patient needs to be urgently reviewed by their specialist.
3. MHRA Drug Safety Update (October 2017): Clozapine: reminder of potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus
   1. the antipsychotic drug 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
   2. 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
   3. advise patients to report constipation immediately and actively treat any constipation that occurs, with an osmotic and/or stimulant laxative
   4. Additional local information and advice is available in the Medicines Optimisation Post Live article here (requires N3 connection)
4. MHRA Drug Safety Update (August 2020): Clozapine and other antipsychotics - monitoring blood concentrations for toxicity. For guidance on monitoring blood concentrations of clozapine, follow the DPT Clinical Protocol for Clozapine CP19.