Prescribing of high-dose and combined antipsychotics for patients on forensic wards.

Transcription

1 POMH-UK Topic 3 baseline May 2007 Prescribing of high-dose and combined antipsychotics for patients on forensic wards. Prepared by the Prescribing Observatory for Mental Health (POMH-UK) for member Healthcare Organisations. This report will be of interest to Executive Teams, Drugs & Therapeutics Committees, Clinical Governance Committees, POMH-UK Local Project Teams, clinicians from participating wards and service user groups. Please use the following to cite this report: Prescribing Observatory for Mental Health (2007). Topic 3 report 3a. Prescribing of highdose and combined antipsychotics for patients on forensic wards: baseline audit 2007 The Royal College of Psychiatrists. For further information contact POMH-uk@cru.rcpsych.ac.uk

2 Glossary of terms Antipsychotics The drugs referred to in this report as antipsychotics are all those included in sections and of the British National Formulary (BNF). Each drug was listed on the data collection form (see Appendix C). First-generation antipsychotics (FGA) First-generation antipsychotics are the older drugs, also known as typicals or typical antipsychotics, as outlined in the BNF, sections and (with the exception of risperidone long-acting injection). Second-generation antipsychotics (SGA) Second-generation antipsychotics are the newer drugs, also known as atypicals or atypical antipsychotics, as outlined in the BNF, section and (risperidone long acting injection only). Antipsychotic Combination Where two or more different antipsychotics are prescribed together this is referred to as combination prescribing. For example, clozapine and olanzapine prescribed together is a combination prescription, but risperidone prescribed for both oral and depot administration is not a combination as this is the same drug administered via two different routes. High-dose of antipsychotic A high-dose is defined as a prescribed total daily dose of a single antipsychotic which exceeds the upper limit stated in the British National Formulary (BNF) or a prescribed total daily dose of two or more antipsychotics which exceeds the BNF maximum using the percentage method. The percentage method is to convert each drug dosage to a percentage of the respective maximum recommended dose; where the percentages added together is above 100%, this is a high-dose. PRN PRN means as required. PRN prescribed doses are included in calculations of total daily dose unless otherwise specified. NICE guidelines The National Institute for Health and Clinical Excellence (NICE) provides guidance on the promotion of good health and the treatment and prevention of ill health based on current evidence from systematic reviews and randomised controlled trials (RCTs);

3 Introduction POMH-UK The Prescribing Observatory for Mental Health (POMH-UK) is a national quality improvement programme open to all NHS, private and not for profit providers of mental health services (Healthcare Organisations; HCOs) in the UK. POMH-UK works with HCOs to help improve prescribing practice in discrete areas ( Topics ) of prescribing practice. For this Topic, participating teams collect data for a baseline audit of their practice. They then have the opportunity to engage in a number of quality improvement interventions before completing a re-audit of practice. This report presents the baseline audit results for Topic 3: Prescribing of high-dose and combined antipsychotics on forensic wards. How to use this report The audit results are divided into three sections: Section 1 summarises the overall national results; Section 2 presents the results for each HCO benchmarked against the national data; Section 3 presents ward level data for your HCO benchmarked against your total HCO sample and the national data. The results presented here allow you to compare your ward/hcos practice against: a. Nationally recognised guidelines; b. The practice of other participating wards in your HCO; c. The practice of other participating HCOs. Data from each ward or HCO are presented by code only; your HCO code is on the front cover. Only the Local Project Team lead for your HCO has the key to your ward codes. You should contact this person if you need to identify data for your own particular ward. Further analysis of your HCO data Ownership of data submitted to POMH-UK is retained by the HCO that provided it. An Excel file containing the data submitted by your HCO has been made available to your Local Project Team lead. Please contact this person if you wish to conduct further analyses on your data.

4 Clinical background The British National Formulary (BNF) provides recommended dose ranges for the licensed antipsychotics in schizophrenia; these can also be found in the Summary of Product Characteristics (SPC) for each drug at These dose ranges are determined in relation to the efficacy and toxicity data for each drug. Clinical guidelines, such as those produced by NICE, recommend that, with a few exceptions, patients should receive one antipsychotic at a time. The evidence base for high-dose antipsychotics While there is considerable evidence for the effectiveness of antipsychotic drugs in the treatment of psychosis (Lehmann and Ban, 1997), there is no evidence to suggest that doses of antipsychotics higher than the recommended dosages are more effective than standard doses (Lehman et al, 1998). This also appears to hold true for cases where standard doses have failed to produce any benefit. The controlled studies comparing very high doses of first-generation antipsychotics with standard dosage regimens for treatment resistant schizophrenia all failed to show a significant advantage for the high dosage (Thompson, 1994; Royal College of Psychiatrists, 2006). Further, higher doses have a greater risk of dose-related side effects. The evidence base for combined antipsychotics Sometimes people receive more than one antipsychotic because they are switching from one antipsychotic to another, and there is cross-tapering of the doses of both drugs in the transition phase. Some people are prescribed a second antipsychotic drug PRN for the management of disturbed behaviour. For others, combined antipsychotics are prescribed because a patient s response to a single antipsychotic has proved less than satisfactory and it is hoped that the addition of another will lead to an enhanced therapeutic effect. The effectiveness and side-effect burden associated with this approach have not been studied systematically in clinical trials (Freudenreich & Goff, 2002). The evidence that does exist suggests that the potential for harm may outweigh the potential for benefit; there is no convincing evidence that symptoms improve (Taylor et al, 2002; Centorrino et al, 2004) and patients who are prescribed combinations are more likely to receive a high total antipsychotic dose (Harrington et al, 2002a), experience side effects and spend longer in hospital (Centorrino et al, 2004). In the longer term, there is tentative evidence that mortality may be increased (Waddington et al, 1998). In 2006, Medicines and Healthcare Regulatory Authority conducted a review of the cardiac safety of all antipsychotics available in the UK (MHRA, 2006). This led to the recommendation that the wording avoid concomitant neuroleptics should be added to the special warnings and precautions for use section of the summary of product characteristics (SPC; product licence) of every antipsychotic. For haloperidol, the most widely used as required antipsychotic in the UK, the SPC also recommends that an ECG should be performed before treatment is started. Recent studies have found that approximately three quarters of those who are prescribed combined antipsychotics in the medium (three months; Kreyenbuhl et al, 2006) and long term (one year; Barbui et al, 2006) are prescribed combinations of FGAs and SGAs (Kreyenbuhl et al, 2006), which is likely to negate the main advantage of SGAs; their lower liability for extrapyramidal side effects (EPS). This notion is supported by the finding that patients prescribed combined SGAs (Carnahan et al, 2006) or combined SGAs and FGAs (Paton et al, 2003) are more likely to be prescribed medication to treat EPS than patients treated with a single SGA.

5 Combined antipsychotics in patients with treatment resistant schizophrenia For people with treatment-resistant schizophrenia who have shown a poor or only partial response to clozapine, the addition of either a first-generation or secondgeneration antipsychotic is a common clinical strategy. However, the research evidence to justify this practice is limited (Chong & Remington 2000), and the results from recent clinical trials are equivocal (Paton et al 2007). Even if there is a response, there are problems in attribution of any benefit seen. If someone is receiving drug A but showing little or no response, and then drug B is added and associated with improvement, there are several possible explanations. The benefit may be due to a little more time on drug A, or related to drug B alone, or related to a pharmacokinetic interaction such that, for example, the plasma level of drug A is increased by the presence of drug B. Only if the positive response were due to a genuine synergistic effect of both drugs would it be worth continuing the combination long-term, but this is difficult if not impossible to determine. Nevertheless, given the nature of the clinical evidence, it is not possible to say that the risk-benefit balance would never favour prescription of an antipsychotic above the BNF recommended maximum dosage, or in combination with another, but prescribing in this way should always be part of an individual clinical trial as Stahl (2002) suggests. Combined antipsychotics should only be considered following lack of response to multiple adequate trials of antipsychotic monotherapy, and then it should be administered as a time-limited trial that is closely monitored, and the combination should only be continued if there is evident therapeutic benefit. Issues relating to forensic services The primary driver for admission to secure-care is violence. In people who have schizophrenia, the risk of violence is increased by the presence of co-morbid antisocial personality disorder (Moran et al, 2003), and further increased by co-morbid substance misuse (Friedman, 2006). Patients in forensic settings are characterised by high levels of personality pathology (Moran, 1999) and substance misuse (Durand et al, 2006) in addition to psychotic illness. The personality pathology is typically from DSM Cluster B, the explosive group, having antisocial and emotionally unstable components, but paranoid elements are also very common. Such patients have typically followed a life course of disadvantage from earliest childhood, and their childhood adversity may be directly linked to their adult vulnerabilities (Coid, 2003, Glaser, 2000). They present to services with violence originating in complex and enduring psychiatric and social problems. The majority of patients in secure settings are detained by court order, and a substantial proportion is also subject to Home Office involvement. Transfers and discharges can be difficult and slow to arrange. Many patients continue to use non-prescribed substances while hospitalised (Main & Gudjonsson, 2006; Durand et al, 2006), substantially reducing the effectiveness of antipsychotic medication (Hunt et al, 2002). The potential consequences of poorly controlled psychotic symptoms, possibly compounded by co-morbid personality disorder and continued substance misuse, include the risk of violence. Effective interventions to reduce this risk, and thereby to allow transfer to a less secure setting, are a priority. For many patients in tertiary settings, all evidence-based pharmacological approaches may have been exhausted.

6 Audit standards Prescribing high-dose antipsychotics The maximum licensed dose for each antipsychotic drug is clearly outlined in its SPC, and in the BNF. The Royal College of Psychiatrists (2006) Council Report 138, a revised consensus statement on high-dose antipsychotic medication, concluded that current evidence did not justify the routine use of high-dose antipsychotic medication. Audit standard 1: The total daily prescribed dose of antipsychotic drugs is within SPC/BNF limits. A high-dose is defined here as a total daily dose (whether of a single antipsychotic or combined antipsychotics) greater than 100% of the maximum recommended daily dose. (Royal College of Psychiatrists, 2006). Prescribing combined antipsychotics NICE has published a Health Technology Appraisal (HTA) on the use of second generation antipsychotics (SGA) in schizophrenia (NICE, 2002), and a treatment guideline for schizophrenia (NICE, 2003). Both the HTA guidance and the NICE treatment guideline contain audit standards that relate to the prescription of more than one antipsychotic drug simultaneously: Audit standard 2: Individuals are prescribed only one antipsychotic at a time. This standard applies to 100% of individuals with schizophrenia. Exceptions: Individuals with schizophrenia who are receiving clozapine but who have not responded sufficiently; and individuals who are changing from one antipsychotic to another (NICE schizophrenia treatment guideline, audit standard 6). Audit standard 3: First (typical) and second generation (atypical) antipsychotic drugs are not prescribed concurrently. This standard applies to 100% of individuals with schizophrenia. Exceptions: Any concurrent prescriptions are for a short period to cover changeover of medication. Local teams should agree on what constitutes a changeover period for audit purposes (NICE HTA 43, audit standard 5).

7 Method The Prescribing Observatory for Mental Health (POMH-UK) invited all NHS, private and not for profit providers of mental health services (Healthcare Organisations; HCOs) in the UK to participate in a national audit of high-dose and combination antipsychotic prescribing. Each HCO that formally agreed to take part was asked to form a Local Project Team (LPT), with suggested membership of a psychiatrist, pharmacist, nurse, clinical governance staff member and at least two service users. Local Project Teams were invited to attend one of five regional introductory workshops to discuss and review the aims, objectives and methodology of the proposed audit. Comment and discussion at the workshops led to refinements of the audit methodology and data collection tool. The participating HCOs were self-selected in that they chose to participate in the audit. They are listed in alphabetical order in Appendix B. Subjects and settings Each LPT was invited to include as many forensic wards as they wished; this included all high and medium secure wards, and step down low-secure wards where a forensic consultant retained clinical responsiblity. Teams were asked to submit data for all patients who, on a census day, occupied a bed on their selected wards and were being prescribed one or more antipsychotic drug(s). To ease the burden of data collection, a different census day (within the period 1-30 March 2007) could be chosen for each ward within the same HCO, but all data for any single ward had to be collected on the same census day. Data collected The following data were collected for all eligible patients: Demographic variables (age, gender, ethnicity) Clinical variables (diagnostic grouping, ward type, length of stay, Mental Health Act and consent to treatment status); Details of prescribed drugs (names and dosage of all regular and PRN antipsychotic drugs prescribed on the census day and the types of other drugs prescribed. Note: For both regular and PRN antipsychotic drugs, the maximum dose that could be administered to a patient over a 24-hour period according to their prescription sheet was recorded, irrespective of whether it was administered or not); Reasons given if high-dose or combination antipsychotics were prescribed (as determined by the clinical team with prescribing responsibility). A copy of the data collection form can be found at the back of this report. Submission of data Each HCO was allocated a code that was known only to itself and POMH-UK. The HCO Local Project Teams were asked to allocate codes to participating wards and eligible patients. The key to these codes is held by the HCO and is not known to POMH-UK. HCOs were given the option of using an additional identifier (to code, for example, individual consultants or clinical teams); again, the key to these codes is held by the HCO team. Data coded in this way were entered onto an internet-based form and submitted to POMH-UK via a secure website.

8 Data analysis Definition of high-dose A high-dose is defined as a prescribed 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 using the percentage method. The percentage method is to convert each drug dosage to a percentage of the respective maximum recommended dose; where the percentages added together is above 100%, this is a high-dose. Definition of combination A patient was considered to be prescribed an antipsychotic combination if they were currently prescribed two or more different antipsychotics. A prescription for the same antipsychotic drug by two or more different routes of administration (e.g. oral and intramuscular) or conditions for administration (e.g. regular and prn) was not classed as a combination. Data were analysed at 3 levels: 1. National data. This section describes the demographic and clinical characteristics, as well as the prevalence of high-dose and combination prescribing, in the total sample. The data were analysed in a variety of ways to facilitate understanding of the national picture and stimulate discussion. 2. HCO level data. The analyses conducted on the national data were repeated for each HCO individually. This allows teams in each HCO to compare the demographic and clinical characteristics of their patients, and their prescribing practice, with the anonymised data from each of the other participating HCOs and the national data set as a whole. 3. Ward level data. For each ward, the proportion of patients prescribed highdose and the proportion receiving combined antipsychotics were calculated. This allows HCO teams to compare prescribing practice across each of their participating wards, and with the national data. Data were collected and analysed using Snap Surveys version 8. All figures are rounded to zero decimal places for clarity of presentation. Therefore the total percentages for some charts or graphs add up to 99% or 101%. The Local Project Team lead for each participating HCO has been sent an electronic copy of their dataset. This allows HCOs to conduct further analyses on their own data should they wish; for example, examination of prescribing practice at the level of individual clinical teams.