Document Title Antipsychotics Prescribing Guidelines for Schizophrenia Document Description Document Type Prescribing Guidance Service Application Medicines Management Version 1.0 Policy Reference no. Lead Author(s) Name Ajibola Gbadebo Job Title Interim Locality Pharmacist - DPH Change History Version Control Version Date Comments 1.0 July 2012 New guidelines issued Link with National Standards National Heath Service Litigation Authority Care Quality Commission National Institute of Clinical 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 Review Date 1
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 in line with CQUIN for 2012/13 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 PCT Walsall PCT 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 2
Document Index Pg 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 7 4.1 Antipsychotic Selection Table 8 4.2 Relative Adverse Effects Profile of Antipsychotic Drugs 9 5 Dosages 9 5.7 Before 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 14 2 Schizophrenia Quick Reference Guide 16 3
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 levels of uptake of 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-resistant illness. 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 is not specific to schizophrenia. 2.3 Target Population: 18-65years 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 and Trust standards for Physical Health monitorings. 3.3 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. 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. 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. A proforma for clinical report will ensure that all information is adequately captured. 4
3.6 All antipsychotic prescribing should be prescribed by their generic names with appropriate formulations stipulated to avoid ambiguities. 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 the dose to the optimum effective dose, or the maximum manufacturers recommended dose or BNF recommendations, evaluating response from two weeks, ensure optimum duration of four to six weeks before switching unless adverse effects occurs. 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. 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 and table (PTO) 5
3.13 Antipsychotics use in Schizophrenia Algorithm 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 Partial or or SGA n-response as single antipsychotic. First episode patients usually require lower antipsychotic dosing and should be closely monitored due to greater sensitivity to medication side effects. FGA daily dosages 300-500 mg chlorpromazine equivalents Duration of therapy: 1 2 years If intolerant or non-adherent, offer Long Acting Injectable antipsychotic Inadequate adherence to oral medication at any stage, may call for a long acting antipsychotic preparation Partial Stage or 2 n-response Trial of a single SGA or FGA different to one tried in stage 1 for up to 4wks Partial or n-response Stage 3 CLOZAPINE Partial or n-response A treatment refractory evaluation should be considered at stage 4-6 Partial or n-response Stage 4 CLOZAPINE + FGA or SGA Stage 5 Trial of a single agent FGA or SGA (not tried in stage 1 or 2) n-response FGA: First Generationantipsychotic SGA: Second Generation Antipsychotic Stage 6 Time limited combination Therapy e.g. SGA + FGA, combination of SGAs (FGA or SGA) & other non antipsychotic agents 6
4 Selecting Antipsychotics for Schizophrenia & Prescribing Formulary In Dudley and Walsall Mental HealthTrust preferred choice of antipsychotics are based on current available evidences with following criteria: Consideration of patients medical history or other co-morbidities e.g. substance abuse & 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 editions of the Maudsley Guidelines, or the Psychotropic Drug Directory (Stephen Bazire) and BNF (www.bnf.org). Key RED AMBER GREEN Antipsychotics that can only be initiated by DWMHPT specialist prescribers, learning disabilities specialists, or practitioners with a special interest in mental health only (non-formulary in all other NHS trusts in the Black Country Cluster) 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. Antipsychotics that may be initiated by medical and non-medical prescribers across the primary and secondary care sections PURPLE BLACK 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 at: <link>. 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 Antipsychotics that should not be prescribed in the Trust 7
4.1 Antipsychotic Selection Table Classification Formulation Comments First Generation Antipsychotics Phenothiazines Chlorpromazine Chlorpromazine Chlorpromazine Suppositories Available from special order manufacturers or specialist importing companies Fluphenazine (unlicensed) Available from special order manufacturers or specialist importing companies Levomepromazine Levomepromazine Pericyazine Perphenazine Prochlorphenazine (Stemetil) Promazine Trifluoperazine Benperidol Haloperidol Haloperidol Flupentixol Zuclopenthixol Zuclopenthixol Acetate Pimozide Amisulpride Sulpiride First Generation Antipsychotics Butyrophenones First Generation Antipsychotics Thioxanthenes First Generation Antipsychotics Diphenylbutylpiperidines First Generation Antipsychotics Substituted Benzamides Second Generation Antipsychotics Aripiprazole Consider less expensive antipsychotic of Aripiprazole Clozapine Olanzapine Olanzapine emboate Paliperidone Quetiapine Risperidone Asenapine Flupentixol decanoate Fluphenazine decanoate Haloperidol decanoate Olanzapine palmoate Paliperidone palmitate Pipothiazine palmitate Risperdal Consta Zuclopenthixol decanoate *** Different oral formulations. Rapid Acting IM Sublingual Depots and Long-Acting s Depot Depot Depot Long Acting Long Acting Depot Long Acting Long Acting equal efficacy, tolerabity and safety first. 8
4.2 Relative Adverse Effects Profile of Antipsychotic Drugs Drug Sedation Weight Gain Diabetes EPSE Ach HTN Prolactin First Generation Antipsychotics (FGAs) Benperidol + + +/- +++ + + +++ Chlorpromazine (oral) Chlorphromazine (IM) +++ ++ ++ ++ ++ +++ +++ Flupentixol (oral) Flupentixol (depot) + ++ + ++ ++ + +++ Fluphenazine (depot) + + + +++ ++ + +++ Haloperidol (oral) Haloperidol (depot) + + +/- +++ + + +++ Levomepromazine Perphenazine Pimozide + + - + + + +++ Prochlorperazine Promazine +++ ++ + + ++ ++ ++ Sulpiride Trifluoperazine + Zuclopenthixol (oral) Zuclopenthixol (depot) ++ ++ + ++ ++ + +++ Second Generation Antipsychotics (SGAs) Amisulpride - + + + - - +++ Aripiprazole - +/- - - - - - Olanzapine (oral) ++ +++ +++ +/- + + + Olanzapine (depot) Paliperidone + ++ + + + ++ +++ Quetiapine ++ ++ ++ - + ++ - Risperidone (oral) + ++ + + + ++ +++ Risperidone (depot) +++: high incidence/severity ++: moderate +:low -:very low. Other side effects include sexual adverse effects, metabolic side effects (The Maudsley Prescribing Guidelines in Psychiatry 2012. 11 th Edition) 5 Dosages 5.1 Dosage titration should be within the range identified in the British National Formulary (BNF) or Summary of Product Characteristics (SmPC). 5.2 Initiation should be at the lower end of the licensed dosage 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. 9
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. 5.7 Before 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 appendix 2). 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 PRN or when required 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 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 riskbenefit 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 > 470ms for men, QTc > 500ms for women) the prescribing should be halted and further advice sought (a cardiology assessment is recommended). 10
5.13 Off-license 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 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 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 or red blood result with clozapine, when switching from one antipsychotic to another (shortterm cross-tapering) and as a temporary measure with depot medication during an acute exacerbation of illness. 5.18 However, 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. 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. 11
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6. Monitoring Requirements 6.1 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 Medication adherence Physical health 6.2 Refer to Trust Physical Health Monitoring Policy on the Trust website for further information 7 Antipsychotics in Special Groups 7.1 All medications should be used in lower doses with children and elderly patients and with great caution in women who are pregnant or breastfeeding 7.1.1 Elderly patients including those with Dementia The use of antipsychotic medications for the treatment of behavioral symptoms in elderly patients with dementia has not been shown to be effective and is associated with an increased risk of mortality. 7.1.2 Pregnancy & Breast Feeding Up to date advice should be obtained and the lowest effective dose used. Specific enquiries regarding the use of antipsychotics during lactation can be addressed to the National Medicines Information Service via their website: www.ukmicentral.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 not breast-feed. (Contact pharmacy for medicines information). 13
Appendix 1 - Data collection tool for Compliance with Antipsychotics in Schizophrenia Formulary / Guidelines Quarter 4 (March 2013) Initials of Data collector: Today s date: Patient identifier: DOB: Male Female Location/Unit: RMO: Initiation Date(s) Current Antipsychotic(s) Frequency & Doses 1. / 2. / 3. / High cost agents therapy 1. If aripirazole was prescribed, was this used as a first line agent? Depot/ long acting injections 2. If paliperidone was prescribed, was this used as a first line agent? 3. If Risperdal Consta was prescribed, was this used as a first line agent? 4. Was the patient initially offered an oral antipsychotic agent? 4(a) If not, was the reason documented? 14
5. Is the antipsychotic(s) prescribed generically 5(a) If not, was the reason documented? 6. Was the dosage(s) of prescribed antipsychotic(s) within the BNF limits? 6(a) If not, was the reason documented? 7. If a patient was prescribed prn (as required) antipsychotic medication, was the clinical indications stated? 8. If a patient was prescribed prn (as required) antipsychotic medication is there evidence that treatment was reviewed in accordance to the Trust guidelines? 9. Is there evidence that the patient received physical health monitoring? 10. Is combination antipsychotic therapy prescribed? 10 (a) If so, was the reason documented? 15
Appendix 2 Schizophrenia Quick Reference Guide Classification Formulation Comments First Generation Antipsychotics Phenothiazines Chlorpromazine Chlorpromazine Chlorpromazine Suppositories Available from special order manufacturers or specialist importing companies Fluphenazine (unlicensed) Available from special order manufacturers or specialist importing companies Levomepromazine Levomepromazine Pericyazine Perphenazine Prochlorphenazine (Stemetil) Promazine Trifluoperazine First Generation Antipsychotics Butyrophenones Benperidol Haloperidol Haloperidol First Generation Antipsychotics Thioxanthenes Flupentixol Zuclopenthixol Zuclopenthixol Acetate First Generation Antipsychotics Diphenylbutylpiperidines Pimozide First Generation Antipsychotics Substituted Benzamides Amisulpride Sulpiride Second Generation Antipsychotics Aripiprazole Consider less expensive antipsychotic of equal efficacy, tolerabity and safety first. Aripiprazole Clozapine Olanzapine Olanzapine emboate Rapid Acting IM Paliperidone Quetiapine Risperidone Asenapine Sublingual Depots and Long-Acting s Flupentixol decanoate Depot Fluphenazine decanoate Depot Haloperidol decanoate Depot Olanzapine palmoate Long Acting Paliperidone palmitate Long Acting Pipothiazine palmitate Depot Risperdal Consta Long Acting Zuclopenthixol decanoate Long Acting Key RED AMBER GREEN PURPLE BLACK Antipsychotics that can only be initiated by DWMHPT or prescribers in primary care with an interest in mental health Antipsychotics which may be initiated by DWMHPT and can be recommended to primary care under a shared care agreement or local enhanced service Antipsychotics that may be initiated by prescribers across the primary and secondary care Antipsychotics that can only be initiated after approval by the Medicines Management Committee via Managed Entry Antipsychotics that should not be prescribed in the Trust 16
DECISION ALGORITHM 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 Partial or n-response Stage 1 First Episode Schizophrenia. Early trial of FGA or SGA as single antipsychotic. First episode patients usually require lower antipsychotic dosing and should be closely monitored due to greater sensitivity to medication side effects. FGA daily dosages 300-500 mg chlorpromazine equivalents Duration of therapy: 1 2 years If intolerant or non-adherent, offer Long Acting Injectable antipsychotic Inadequate adherence to oral medication at any stage, may call for a long acting antipsychotic preparation Partial Stage or n- 2 Trial of a single SGA or FGA different to one tried in stage 1 for up to 4wks Partial or n-response Stage 3 CLOZAPINE Partial or n-response Stage 4 CLOZAPINE + FGA or SGA A treatment refractory evaluation should be considered at stage 4-6 Partial or n-response Stage 5 Trial of a single agent FGA or SGA (not tried in stage 1 or 2) n-response Stage 6 Time limited combination Therapy e.g. SGA + FGA, combination of SGAs (FGA or SGA) & other non antipsychotic agents FGA: First Generationantipsychotic SGA: Second Generation Antipsychotic 17