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Document Title

Antipsychotics Prescribing Guidelines for Schizophrenia

Document Description

Document Type Prescribing Guidance

Service Application Medicines Management

Version 1.3

Policy Reference no. POL 249

Lead Author(s)

Name Job Title

Linda Geddes Senior Pharmacist (DGNFT)

Andrew Campbell Chief Pharmacist (DWMHPT)

Amandeep Dhillon Locality Pharmacist (DWMHPT)

Change History – Version Control

Version Date Comments

1.0 14/11/2012 New guidelines issued agreed by Policies and Procedures Focus Group 25/10/2012 and formally ratified by Governance and Quality Committee 14/11/2012

1.1 04/09/2014 Policy updated and formally ratified by Policies and Procedures Focus Group

1.2 21/09/2015 Updated antipsychotic dosage ready reckoner – version 6, page 12

1.3 28/11/2016 Planned policy update and review

Link with National Standards

National Health Service Litigation Authority

Care Quality Commission

National Institute for Health and Care Excellence (NICE) Guidance

National Patient Safety Agency

West Midlands Quality Review

Essence of Care

Aims Standards

IG Toolkit

Key Dates Day Month Year

Ratification Date 04 09 2014

Review Date 04 09 2018

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Executive Summary Sheet

Document Title: Antipsychotics Prescribing Guidelines for Schizophrenia

Please tick () as appropriate

This is a new document within the Trust

This is a revised document within the Trust

What is the purpose of this document?

To provide guidance on the pharmacological treatment available for schizophrenia with Dudley and Walsall Mental Health Partnership NHS Trust (DWMHPT). Guidance to be audited annually (see appendix 1).

What key issues does this document explore?

Drug choice and Monitoring recommendations for Schizophrenia

Who is this document aimed at?

All DWMHT clinic service leads, all clinicians including medical, non medical prescribers and Pharmacists Business Administration Managers General Practitioners Dudley CCG Walsall CCG

What other policies, guidance and directives should this document be read in conjunction with?

Medicines Management Policy Physical Health Monitoring Policy

How and when will this document be reviewed?

Annually via the Medicines Management Committee

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Document Index Pg No

1. Introduction 4

2. Scope 4

3. Recommended Procedure for Antipsychotic Use 4

3.13 Antipsychotics use in Schizophrenia Algorithm 6

4. Selecting Antipsychotics for Schizophrenia & Prescribing Formulary

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4.1 Antipsychotic Selection Table 8

4.2 Relative Adverse Effects Profile of Antipsychotic Drugs 9

5. Dosages 9

5.7 Prescribing High Dose Antipsychotics 10

5.20 Equivalent doses of Antipsychotics 11

6. Monitoring Requirementts 13

7. Antipsychotics in Specials Groups 13

7.1.1 Elderly patients including those with Dementia 13

7.1.2 Pregnancy & Breast Feeding 13

Appendices Pg no

1 Data collection tool for Compliance with Antipsychotics in ‘Schizophrenia’ Formulary / Guidelines

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2 Schizophrenia Quick Reference Guide 16

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1 Introduction 1.1 Schizophrenia is usually accompanied by other co-morbid illnesses such as

anxiety, substance misuse and depression. Antipsychotics should only be prescribed by a specialist psychiatrist. There is no first line antipsychotic drug which is suitable for all patients.

1.2 This document reflects current NICE guidelines on Schizophrenia. It is strongly

advised that the use of these recommendations should be balanced with consideration of the patient’s clinical circumstances, their preferences and attitudes.

1.3 Prescribing audits will be undertaken to check standards and compliance with this

prescribing guideline 2 Scope 2.1 The guideline covers antipsychotic use in the management and treatment of

schizophrenia across the various stages of the illness, including prodromal presentations, first-episode, relapse prevention and treatment-resistance.

2.2 It is beyond the scope of this guideline to include a recommended approach to

treatment in pregnancy states, breast feeding patients and rapid tranquillization, which are not specific to schizophrenia.

2.3 Target Population: 18 – 65 years of age diagnosed with schizophrenia. 3 Recommended Procedure for Antipsychotic Use 3.1 Initiation of antipsychotic treatment for schizophrenia should be by specialist

psychiatrist. 3.2 ECG and other necessary investigations should be checked before antipsychotics

are prescribed in accordance with NICE guidelines, the Summary Product Characteristics (SPC) and the Trust standards for Physical Healthcare Policy.

3.3 Oral antipsychotics should be offered first. 3.4 Patient and carers should be duly provided appropriate information to enable jointly

made decisions to improve patient experience and concordance with therapy (see Choice and Medication website). A decision about which medicine is prescribed should be made jointly with the individual based on an informed discussion of the relative benefits and side effects of medicines which includes the following:

Metabolic (including weight gain and diabetes)

Extrapyramidal (includes akathisia, dyskinesia and dystonia)

Cardiovascular (Includes prolonging the QT interval)

Hormonal (includes increasing prolactin levels)

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3.5 Adequate documentation (clinical rating scale information, response to treatment, full details of medications used, and the rationale for changing medication) should be completed for each treatment choice. Record the indications and expected benefits and risk of oral medication and expected time for change in symptoms and appearance of side effects.

3.6 All antipsychotic prescribing should be prescribed by their generic names with appropriate formulations stipulated to avoid ambiguities and related errors.

3.7 Where a choice exists between brand, generic, or different formulations (e.g. slow

release) of a recommended antipsychotic, initiate treatment with a form that is likely to be best tolerated to enhance adherence with treatment.

3.8 The antipsychotic should be initiated at a low dose and slowly titrate to the

optimum effective dose, or the maximum manufacturers recommended dose or BNF recommendations. Evaluate response from two weeks, and ensure optimum duration of four to six weeks before switching unless adverse effects occur.

3.9 Where there is no/insufficient response after maintaining the maximum tolerated

dose for at least four weeks the antipsychotic should be withdrawn gradually, whilst introducing an alternative antipsychotic. Record the rationale for continuing, changing or stopping the medication and the effects of such changes.

3.10 Sedatives may be required for short term behavioural control if needed. 3.11 If any steps of treatment differ from the recommendation, the rationale should be

adequately documented. 3.12 Recommendations are illustrated in the following algorithm - 3.13.

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3.13 Antipsychotics use in Schizophrenia Algorithm

Partial or Non-response

Partial or Non-response

FGA: First Generation antipsychotic SGA: Second Generation Antipsychotic If chlorpromazine is prescribed warn of its potential to cause skin photosensitivity. Advise using sunscreen if necessary.

Stage 3 CLOZAPINE

Choice of antipsychotic (AP) should be guided by considering the clinical characteristics of the patient and the efficacy and side effect profiles of the medication. Stages may be skipped depending on the clinical picture or history of antipsychotic failures. Returning to an earlier

stage may be justified by history of past response

Stage 1 First Episode Schizophrenia. Early trial of FGA or SGA as single antipsychotic in

conjunction with psychological interventions (family interventions and individual CBT). First episode patients usually require lower antipsychotic dosing and should be closely monitored due to

greater sensitivity to medication side effects. Duration of therapy: 1–2 years.

If intolerant or non-adherent, offer Long Acting Injectable antipsychotic.

Stage 5 Trial of a single agent

FGA or SGA (not tried in stage 1 or 2)

Stage 2 Trial of a single SGA or FGA different to one tried in stage 1 for up to 4wks

Stage 4 CLOZAPINE

+ FGA or SGA (An adequate trial of such an augmentation may need to be up to 8-10

weeks)

Stage 6 Time limited combination therapy e.g. SGA + FGA, combination of SGAs (FGA or SGA) & other non

antipsychotic agents

A treatment

refractory

evaluation

should be

considered at

stage 4 -6

Partial or Non-response

Partial or Non-response

Partial or Non-response

Non-response

Inadequate adherence to

oral medication at any

stage, may call for a long

acting antipsychotic

preparation (Initially use

a small test dose as set

out in the BNF or SPC).

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4 Selecting Antipsychotics for Schizophrenia & Prescribing Formulary In Dudley and Walsall Mental Health Partnership NHS Trust preferred choice of antipsychotics are based on current available evidence with the following criteria:

Consideration of patients’ medical history or other co-morbidities e.g. substance abuse, smoking (impact on metabolism on drugs particularly clozapine and olanzapine) and medication history.

The relative importance of side effect profile of the antipsychotic to the patients.

Acquisition costs of different available therapies: Consideration should always be given to medication acquisition cost. If all other things are equal (i.e. efficacy, safety, tolerability), then less expensive antipsychotic relevant to the clinical situation should be the first choice

Longer term clinical and economic outcomes

Formulation of antipsychotics Prescribers are advised to refer to the latest edition of the Maudsley Guidelines, the Psychotropic Drug Directory (Stephen Bazire) and the BNF (https://www.evidence.nhs.uk/formulary/bnf/current). Key RED Antipsychotics that can only be initiated by DWMHPT specialist prescribers,

learning disabilities specialists, or practitioners with a special interest in mental health only.

AMBER Antipsychotics which may be initiated by DWMHPT specialist prescribers and can

be recommended to GP or other prescriber involved in the care of the patient in the primary care community, under a shared care protocol and local enhanced services. “Continuing care guidance” with continuing support may be provided by the DWMHPT, where appropriate.

GREEN Antipsychotics that may be prescribed by medical and non-medical prescribers

across the primary and secondary care interface if initiated by a specialist psychiatrist.

PURPLE Antipsychotics that can only be initiated after approval by the Medicines

Management Committee or through the approved process specified by the Medicines Management Committee. The Managed Entry process can be found on trust website. All newly introduced psychotropic drugs and new formulations of existing ones are automatically restricted for use in the Trust until the Dudley and Walsall Medicines Management Committee (MMC) undertake informed evaluation of its use and place in therapy within the Trust

BLACK Antipsychotics that should not be prescribed in the Trust

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4.1 Antipsychotic Selection Table

Classification Formulation Comments

First Generation Antipsychotics Phenothiazines

Chlorpromazine Oral

Chlorpromazine Injection

Chlorpromazine Suppositories Available from’special order’ manufacturers or specialist importing companies

Fluphenazine Oral (unlicensed) available from ‘special order’ manufacturers or specialist importing companies

Levomepromazine Oral

Levomepromazine Injection

Pericyazine Oral

Perphenazine Oral

Prochlorphenazine (Stemetil) Oral

Promazine Oral

Trifluoperazine Oral

First Generation Antipsychotics Butyrophenones

Benperidol Oral

Haloperidol Oral

Haloperidol Injection Oral

First Generation Antipsychotics Thioxanthenes

Flupentixol Oral

Zuclopenthixol Oral

Zuclopenthixol Acetate Injection

First Generation Antipsychotics Diphenylbutylpiperidines

Pimozide Oral

First Generation Antipsychotics Substituted Benzamides

Amisulpride Oral

Sulpiride Oral

Second Generation Antipsychotics

Aripiprazole Oral Consider less expensive antipsychotic of equal efficacy, tolerabity and safety first.

Aripiprazole Injection Injection

Clozapine Oral

Lurasidone Oral

Olanzapine Oral

Olanzapine emboate Rapid Acting IM Injection

Paliperidone Oral

Quetiapine Oral

Risperidone Oral

Asenapine Sublingual

Depots and Long-Acting Injections

Flupentixol decanoate Depot Injection

Fluphenazine decanoate Depot Injection

Haloperidol decanoate Depot Injection

Olanzapine palmoate Long Acting

Paliperidone palmitate Long Acting

Risperdal Consta Long Acting

Zuclopenthixol decanoate Long Acting

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4.2 Relative Adverse Effects Profile of Antipsychotic Drugs

Drug Sedation Weight

gain

Akathisia Parkinsonism Anti-

cholinergic

Hypotension Prolactin

elevation

Amisulpride - + + + - - +++

Aripiprazole - - + - - - -

Asenapine + + + - - - +

Benperidol + + + +++ + + +++

Chlorpromazine +++ ++ + ++ ++ +++ +++

Clozapine +++ +++ - - +++ +++ -

Flupentixol + ++ ++ ++ ++ + +++

Fluphenazine + + ++ +++ ++ + +++

Haloperidol + + +++ +++ + + ++

Iloperidone - ++ + + - + -

Loxapine ++ + + +++ + ++ +++

Lurasidone + - + + - - +

Olanzapine ++ +++ + - + + +

Paliperidone + ++ + + + ++ +++

Perphenazine + + ++ +++ + + +++

Pimozide + + + + + + +++

Pipothiazine ++ ++ + ++ ++ ++ +++

Promazine +++ ++ + + ++ ++ ++

Quetiapine ++ ++ - - + ++ -

Risperidone + ++ + + + ++ +++

Sertindole - + - - - +++ -

Sulpiride - + + + - - +++

Trifluoperazine + + + +++ + + +++

Ziprasidone + - + - - + +

Zuclopentixol ++ ++ ++ ++ ++ + +++

+++ high incidence/severity, ++ moderate, + low, - very low

(The Maudsley Prescribing Guidelines in Psychiatry 2015. 12th Edition)

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5 Dosages

5.1 Dosage titration should be within the range identified in the British National

Formulary (BNF) or Summary of Product Characteristics (SPC). 5.2 Initiation should be at the lower end of the licensed dose range and increased

gradually, depending on response or behaviour and the nature and tolerability of side effects, aiming to achieve an adequate trial at the optimum dosage with good adherence.

5.3 Any dose increase of antipsychotic should be performed gradually at a minimum of

weekly intervals. This will help to identify a clinical response at the lowest effective dose and may reduce the risk of neuroleptic malignant syndrome.

5.4 There is no evidence that dosages above the recommended range have any

advantage in the treatment of acute psychotic episodes. 5.5 Regular combined antipsychotic medication should not be prescribed routinely,

except for short periods when switching from one antipsychotic to another or in a time limited trial where there is a partial response after trial of successive agents.

5.6 Doses above the usual therapeutic range should be time limited (e.g. 4-6 weeks)

and response evaluated using standard clinical ratings. If improvement has not occurred with the higher than usual dosage in this time frame, then treatment should be reviewed.

5.6.1 Do not use a loading dose of antipsychotic medication (often referred to

as ‘rapid neuroleptisation’).

5.7 Prescribing High Dose Antipsychotics: 5.7.1 High dose antipsychotic therapy (HDAT) is defined by the Royal College of

Psychiatrists (RCPsych) as a total daily dose of a single antipsychotic which exceeds the upper limit stated in the British National Formulary (BNF), or a total daily dose of two or more antipsychotics which exceeds the BNF maximum as calculated by percentages using the antipsychotic dose ready reckoner (see page 13).

5.7.2 Example calculation:

Zuclopenthixol depot 300mg weekly (50%) and olanzapine 15mg daily (75%) = 50% + 75%= 125% (>100% therefore ‘high dose’)

5.8 Current evidence does not justify the routine use of HDAT. If high doses are to be

used in an individual case this should be time limited, with clear reasons and treatment plan documented in the patients notes.

5.9 Use of ‘when required’ or ‘PRN’ antipsychotic medication should also be included

in calculating the total daily dose. The use of PRN medication should be reviewed regularly.

5.10 Practitioners administering doses of antipsychotics above BNF maximum doses

must check the notes for the rationale behind this decision and confirm that the

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dose is documented in the notes or should assure themselves of the rationale for high dose prescribing.

5.11 The decision to prescribe HDAT should involve an individual risk-benefit

assessment by a Consultant Psychiatrist, the patient (where possible) and the multidisciplinary team

5.12 A baseline ECG should be performed to exclude cardiac contraindications such as

QT prolongation. If an ECG is not performed, the reason should be documented in the patients’ notes. The ECG should be repeated after a few days, and then every one to three months in the early stages of high dose treatment and then periodically as clinically indicated. In the event of a prolonged QT interval (QTc >500msec) then prescribing should be halted and further advice sought (a cardiology assessment is recommended).

5.13 Unlicensed or off-label would apply to the use of HDAT and must be considered and discussed with the patient. Any discussion and decision reached should be documented in the notes including the risks and benefits, the aims and when and how the outcome will be assessed.

5.14 Therapeutic progress should be monitored at least once every three months,

preferably with the aid of a rating scale such as the Positive and Negative Symptoms of Schizophrenia Scale (PANSS) or the Brief Psychiatric Rating Scale (BPRS). If no significant progress is observed then the use of HDAT should cease and the future treatment plan should be reviewed. Continued use of HDAT where there is no improvement in clinical response must be fully and clearly justified in the case notes. In this instance the responsible medical officer should consider seeking a second opinion from another senior colleague.

5.15 The justification for dosages outside the range given in the BNF or SmPC and

target outcomes of the HDAT should also be documented in the clinical records. 5.16 Before HDAT is used the diagnosis and previous treatment should be reviewed,

including doses and duration. Concordance with treatment should be reviewed and alternative antipsychotics and adjunctive drug therapies should have been considered.

5.17 In a small proportion of cases HDAT may be justified provided the safety

implications are considered and monitoring requirements are observed. These include; partial response, when clozapine has failed or when switching from one antipsychotic to another (short-term cross-tapering) and as a temporary measure with depot medication during an acute exacerbation of illness.

5.18 There is insufficient evidence for the use of HDAT for relapse prevention in

schizophrenia, persistent aggression and treatment resistant schizophrenia. 5.19 Consideration should also be given to the increased treatment costs associated

with HDAT and the possibility of GPs being unwilling to assume prescribing responsibility after the patient is discharged if HDAT is being used.

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5.20 Equivalent doses of Antipsychotics:

Antipsychotics vary greatly in potency and are expressed as differences in ‘chlorpromazine’ equivalents. These values should be seen as a rough guide when transferring from one conventional drug to another. The dose-response relationship is usually well defined for SGAs, and it is inappropriate to convert second generation antipsychotic dose into ‘equivalents.’

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7 Monitoring Requirements 7.1 Regular review of the medication regimen should address the following:

Therapeutic efficacy, in terms of change in clinical domains such as symptoms, behaviour and cognition

Side effects of treatment (includes emergence of movement disorders)

Medication adherence

Blood pressure, pulse, weight, waist circumference and fasting blood glucose

Physical health 7.2 Refer to Trust Physical Healthcare Policy on the Trust website for further information.

8 Antipsychotics in Special Groups

8.1 All medications should be used in lower doses with children and elderly patients and with

great caution in women who are pregnant or breastfeeding.

8.1.1 Elderly patients including those with Dementia

The use of antipsychotic medications for the treatment of behavioural symptoms in elderly patients with dementia has not been shown to be effective and is associated with an increased risk of mortality.

8.1.2 Pregnancy & Breast Feeding

Up to date advice should be obtained and the lowest effective dose used. Specific enquiries regarding the use of antipsychotics during pregnancy can be found on the www.toxbase.org website under exposure in pregnancy. Lactation advice can be obtained via the UK drugs in lactation advisory service www.midlandsmedicines.nhs.uk. The benefits of breast-feeding to the mother and infant must be weighed against the risks due to exposure in the infant. A treatment that allows breast-feeding should be explored rather than recommending to not breast-feed (if necessary contact pharmacy for further medicines information).

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Appendix 1 - Data collection tool for Compliance with Antipsychotics in ‘Schizophrenia’ Formulary / Guidelines

Initials of Data collector: Today’s date:

Patient identifier: DOB:

Male Female Location/Unit: Cons:

Initiation Date(s) Current Antipsychotic(s) Frequency & Doses 1. __ __/__ __ _______________________________ _____________________ 2. __ __/__ __ _______________________________ _____________________ 3. __ __/__ __ _______________________________ _____________________

1. Is there evidence that the patient received physical health checks prior to antipsychotic initiation and periodically as per physical health policy?

Yes No

2. Is the antipsychotic(s) prescribed generically

Yes No

(a) If not, was the reason documented?

Yes No

3. Is combination antipsychotic therapy prescribed?

Yes No

(a) If so, was the reason documented?

Yes No

4. Is the dosage(s) of prescribed antipsychotic(s) within the BNF limits?

Yes No

(a) If not, was the reason documented?

Yes No

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5. Is the patient on a depot antipsychotic injection?

Yes No

(a) If so, was the reason documented?

Yes No

6. Was the patient initially offered an oral antipsychotic agent?

Yes No

(a) If not, was the reason documented?

Yes No

7. If Paliperidone or Risperdal consta been prescribed for the first time has the approval paper work been completed?

Yes No

(a) Has tolerability to oral risperidone been established?

Yes No

8. If Aripiprazole long acting depot injection been prescribed for the first time has the approval paperwork been completed?

Yes No

(a) Has tolerability to oral Aripiprazole been establised?

Yes No

(b) was the oral Aripiprazole continued for at least 2 weeks after the first depot injection?

Yes No

9. If patient was prescribed prn (as required) antipsychotic medication, was the clinical indication stated?

Yes No

10. If patient was prescribed prn (as required) antipsychotic medication is there evidence that treatment was reviewed in accordance with the trust guidance?

Yes No

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11. Before switching from one antipsychotic to the next has an adequate duration of treatment been established with the first treatment (unless adverse effects) usually between 4-6 weeks?

Yes No

(a) If not, was the reason documented?

Yes No

12. For patients on high dose antipsychotics is the rational for this qualified and documented in the notes?

Yes No

(a) Has this been discussed with the patient?

Yes No

(a) If no improvement beyond 4-6 weeks has treatment been reviewed?

Yes No

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Appendix 2 – Schizophrenia Quick Reference Guide Classification Formulation Comments

First Generation Antipsychotics Phenothiazines

Chlorpromazine Oral

Chlorpromazine Injection

Chlorpromazine Suppositories Available from’special order’ manufacturers or specialist importing companies

Fluphenazine Oral (unlicensed) available from ‘special order’ manufacturers or specialist importing companies

Levomepromazine Oral

Levomepromazine Injection

Pericyazine Oral

Perphenazine Oral

Prochlorphenazine (Stemetil) Oral

Promazine Oral

Trifluoperazine Oral

First Generation Antipsychotics Butyrophenones

Benperidol Oral

Haloperidol Oral

Haloperidol Injection Oral

First Generation Antipsychotics Thioxanthenes

Flupentixol Oral

Zuclopenthixol Oral

Zuclopenthixol Acetate Injection

First Generation Antipsychotics Diphenylbutylpiperidines

Pimozide Oral

First Generation Antipsychotics Substituted Benzamides

Amisulpride Oral

Sulpiride Oral

Second Generation Antipsychotics

Aripiprazole Oral Consider less expensive antipsychotic of equal efficacy, tolerabity and safety first.

Aripiprazole Injection Injection

Clozapine Oral

Lurasidone Oral

Olanzapine Oral

Olanzapine emboate Rapid Acting IM Injection

Paliperidone Oral

Quetiapine Oral

Risperidone Oral

Asenapine Sublingual

Depots and Long-Acting Injections

Flupentixol decanoate Depot Injection

Fluphenazine decanoate Depot Injection

Haloperidol decanoate Depot Injection

Olanzapine palmoate Long Acting

Paliperidone palmitate Long Acting

Risperdal Consta Long Acting

Zuclopenthixol decanoate Long Acting Key RED Antipsychotics that can only be initiated by DWMHPT or prescribers in primary care with an interest in mental health AMBER Antipsychotics which may be initiated by DWMHPT and can be recommended to primary care under a shared care

agreement or local enhanced service GREEN Antipsychotics that may be initiated by prescribers across the primary and secondary care PURPLE Antipsychotics that can only be initiated after approval by the Medicines Management Committee via Managed Entry BLACK Antipsychotics that should not be prescribed in the Trust