Antipsychotic Prescribing Audit:

Antipsychotic Prescribing Audit: Measuring the impact of a prescribing intervention Audit Co-ordinator/ Author of Report: Supervisor: Professor Shôn W Lewis

Table of Contents List of Tables... 3 List of Figures... 4 Executive Summary... 5 Recommendations... 8 Limitations... 9 Introduction...10 Standards...11 Definition...13 Aim...13 Method...13 Power calculation & sample size...14 Pre-Intervention Audit: Antipsychotic Prescribing Rates...15 Antipsychotic monotherapy prescribing...17 Combination antipsychotic prescribing...19 High Dose antipsychotic prescribing...24 Summary: Pre-Intervention Prescribing Audit...30 Prescribing Intervention...31 Post-Intervention Antipsychotic Prescribing Audit...32 Monotherapy prescribing...33 Combination Antipsychotic Prescribing...35 High Dose antipsychotic prescribing...40 Summary: Post-Intervention Antipsychotic Prescribing...47 Effectiveness of Intervention...48 Rates & Pattern of Combination Prescribing...48 High Dose Prescribing (Chlorpromazine equivalents)...49 High Dose Prescribing (Percentage Maximum BNF Recommended Dose)...50 Change in pattern of prescribing...51 Pattern of antipsychotic monopharmacy...53 Clozapine Prescribing Rates...54 Change in pattern of antipsychotic prescribing between the two time-points...55 Acknowledgements...58 References...59 2

List of Tables Table Title Page 1 Pre-Intervention Audit: audit sample vs. overall population 15 2 Pre-Intervention Audit: characteristics of samples 16 3 Oldham (Intervention) Site: antipsychotic drugs prescribed to monotherapy group 17 4 Stockport (Control) Site: antipsychotics prescribed to monotherapy group 18 5 Oldham (Intervention) Site: antipsychotic drugs co-prescribed 21 6 Stockport (Control) Site: antipsychotic drugs co-prescribed 23 7 Oldham (Intervention) Site: high dose prescribing (CPZEq) 24 8 Stockport (Control) Site: high dose prescribing (CPZEq) 25 9 Pre-Intervention Prescribing Audit: CPZEq doses 26 10 Oldham (Intervention) Site: high doses (>100% Max BNF Dose) 27 11 Stockport (Control) Site: high doses (>100% Max BNF Dose) 28 12 Pre-Intervention Prescribing Audit: %MaxBNF doses 29 13 Oldham (Intervention) Site: antipsychotic drugs prescribed as monotherapy 33 14 Stockport (Control) Site: antipsychotic drugs prescribed as monotherapy 34 15 Oldham (Intervention) Site: antipsychotic drugs co-prescribed 37 16 Stockport (Control) Site: antipsychotic drugs co-prescribed 39 17 Oldham (Intervention) Site: high dose prescribing (CPZEq) 40 18 Stockport (Control) Site: high dose prescribing (CPZEq) 41 19 Post-Intervention Prescribing: CPZEq doses 42 20 Oldham (Intervention) Site: high doses (>100% Max BNF Dose) 44 21 Stockport (Control) Site: high doses (>100% Max BNF Dose) 45 22 Post-Intervention Prescribing Audit: %MaxBNF doses 46 23 Pattern of prescribing: Pre-Intervention to Post-Intervention 51 24 High Dose Rates: Pre-Intervention to Post-Intervention 52 25 High Dose Rates: Pre-Intervention to Post-Intervention 52 3

List of Figures Fig. Title Page 1 Pre-Intervention pattern of co-prescribing: Oldham 20 2 Pre-Intervention pattern of co-prescribing: Stockport 22 3 Post-Intervention pattern of co-prescribing: Oldham 36 4 Post-Intervention pattern of co-prescribing: Stockport 38 4

Antipsychotic Prescribing Audit: Measuring the impact of a prescribing intervention Executive Summary Design A prescribing intervention was designed, informed by a comprehensive systematic review and comprising an educational aspect involving an opinion leader and individual, outreach-type visits and a reminder system to alert clinicians to current cases of combination and high dose antipsychotic prescribing. Results Antipsychotic co-prescribing Post-intervention rates of co-prescribing in the Oldham (intervention) site (20%) did not differ statistically from either those in the same site pre-intervention (22%) or those in the Stockport (control) site post-intervention (14%) in a sufficiently powered study. Samples from the two sites were reasonably comparable pre-intervention. The most commonly-used antipsychotic combination in both sites before and after the intervention was olanzapine together with flupenthixol depot. High dose antipsychotic prescribing The use of the percentage of maximum recommended BNF dose as the definition for high dose prescribing gave a rate of about twice that seen with the use of a chlorpromazine equivalents conversion. Post-intervention rates of high dose prescribing in the Oldham (intervention) site (6% CPZEq/ 12% Max BNF dose) did not differ statistically from either those in the same site pre-intervention (5% CPZEq/ 9% Max BNF dose) or those in the Stockport (control) site post-intervention (6% CPZEq/ 10% Max BNF dose). Treatment with combination therapy was associated with significantly higher dose prescribing, in both sites, regardless of the definition used. 5

New case rate The number of new, or inception, cases of co-prescribing (patients switched from monotherapy to combination therapy) were low in both sites. Similarly, a low number of patients (less than four per cent in both sites, regardless of definition used) had their treatment switched from standard dose therapy to high dose therapy. Clozapine prescribing Rates of clozapine prescribing were higher in the Stockport (control) site (22% preand post-intervention) compared with the Oldham (intervention) site (16% pre- and post-intervention) but rates did not differ statistically between the two locations. Clozapine co-prescribing Pre- and post-intervention samples in the two sites highlighted that the addition of a second antipsychotic drug to clozapine therapy comprised between 6% and 16% of combination-treated patients and between 1% and 3% of the sample overall. This finding will be useful when auditing rates of combination prescribing as such coprescribing is permitted in widely-used clinical treatment guidelines such as NICE. Antipsychotic switches Although rates of combination and high dose prescribing were relatively consistent throughout the timeperiod, across both sites 17% of patients (almost one in six) experienced a switch in their antipsychotic drug over the period of the study. Between 18% and 20% of patients in both sites were subject to antipsychotic dose changes. In the Stockport (control) site there were a number of statistically significant findings relating to antipsychotic drug switches, with patients most likely to switch treatment between the two time-points being treated with antipsychotics in combination rather than monotherapy; treated with a non-clozapine SGA rather than clozapine; and on a higher dose (%Max BNF) than non-switchers at the baseline audit. 6

Conclusions A multifaceted prescribing intervention failed to reduce rates of combination antipsychotic prescribing post-intervention compared with rates seen pre-intervention and rates seen in a site where the intervention did not take place. Baseline rates of antipsychotic co-prescribing in both sites were substantially lower than those seen in national prevalence data. 7

Recommendations A number of the recommendations made following the previous audit of antipsychotic prescribing are repeated here as they remain important issues. 1. Clearer recording in patient casenotes, especially of current antipsychotic drug treatment (drug and dose) is required. 2. A reduction in the rate of combination antipsychotic prescribing is required. One in five patients in the Oldham site and around one in seven in the Stockport site received treatment with a combination of antipsychotic drugs. A minority of these were treated with three antipsychotic drugs concurrently. All current treatment guidelines advise against such prescribing except for the addition of a second antipsychotic drug to clozapine in treatment-resistant schizophrenia, following an adequate trial of clozapine monotherapy. The definition of coprescribing used here of receipt of such treatment for more than one month means that patients in the process of switching from one antipsychotic to another will comprise a small proportion of this figure. 3. A reduction in the rate of high dose antipsychotic prescribing is required. Depending on the definition employed, between five and twelve per cent of patients received a high dose of antipsychotic drug treatment. More coprescribed patients were receiving high dose treatment compared with monotherapy-treated patients, providing further evidence for the necessity of a reduction in rates of combination antipsychotic treatment. 4. Rates of combination and high dose antipsychotic prescribing do not form routinely collected prescribing data, despite the adverse events associated with both of these practices. More accurate and straightforward methods of collecting such important data require further exploration. 5. It is, as yet, unclear whether the new patient electronic records system (NCRS) will ease data collection for antipsychotic prescribing audits. 8

Limitations It took longer than anticipated to collect prescribing data prior to and following the use of the intervention package and to collect data on a sufficient number of patients to satisfy the requirements of the power calculation. Data collection covered the Christmas/ New Year period when attendance at outpatient clinics fell substantially at both sites. Data collection therefore had to carry on well beyond the planned threemonth period. Similarly, the time-consuming nature of the audit overall, particularly as it involved collected the majority of data via patient casenotes, may well have led to inaccuracies in data recording. The cross-sectional nature of audit data means that caution must be attached in inferring the direction of causality of any significant findings. 9

Introduction Prescribing antipsychotic drugs in combination increases the incidence of adverse drug effects and multiplies treatment costs, with no formal evidence for increased efficacy (Hamann et al, 2003; Taylor et al, 2000; Yuzda, 2000). Receiving combined high doses of antipsychotics may be an inadvertent consequence of co-prescribing (Bingefors et al, 2003; Lelliott et al, 2002) with 20% of UK patients receiving antipsychotics in doses exceeding BNF guidance (BNF, 2007; Harrington et al, 2002; Hayhurst et al, 2007). The previous audit of antipsychotic prescribing carried out in Pennine Care NHS Trust, demonstrated that rates of combination antipsychotic prescribing and high dose antipsychotic prescribing differed significantly from zero (for example, in Oldham, 20% of patients received combination antipsychotic treatment and 15% were treated with high dose antipsychotic treatment). The report of this previous audit can be found using the following link: www.burypct.nhs.uk/fileadmin/user_upload/health_promotion/test_page_2/paul/sigma_05.pdf 10

Standards The main clinical treatment guidelines in force in the UK guard against the use of antipsychotic polypharmacy, or combination prescribing. National Institute for Health & Clinical Excellence (NICE, 2002a) guidance on the use of newer (atypical) antipsychotic drugs for the treatment of schizophrenia states that, atypical and typical antipsychotic drugs should not be prescribed concurrently, except for short periods to cover changeover of medication This guidance was repeated in the NICE (2002b) Core Interventions guidance, although combination prescribing was permitted under certain circumstances, the addition of a second antipsychotic drug to clozapine may be considered for people with treatment resistant schizophrenia for whom clozapine has proved insufficiently effective The Royal College of Psychiatrists Consensus statement on high dose antipsychotic prescribing was recently revised (May 2006) and states, the efficacy of combining two or more FGAs or adding a FGA to a SGA (or vice versa) has not been established and there is evidence for increased risk of adverse effects and pharmacokinetic interactions Local (Greater Manchester) SiGMA guidelines state that, the co-prescribing of two or more antipsychotic drugs at the same time, including atypical with typical drugs, apart from transitional periods, has no proven advantages in general, with disadvantages including increased side effects and difficulty in calculating the total cumulative dose being taken 11

The British National Formulary (BNF, 2006) states, the prescribing of more than one antipsychotic at the same time is not recommended as this may constitute a hazard The Maudsley prescribing guidelines (2005-2006) suggest that, antipsychotic monotherapy is desirable and should be the norm polypharmacy should be undertaken only where response to a single antipsychotic (including clozapine) has been clearly demonstrated to be inadequate - in such cases, the effect of polypharmacy should be carefully evaluated and documented - where there is no clear benefit, treatment should revert to single antipsychotic therapy 12

Definition: patients were classed as receiving combination antipsychotic treatment based on an operational definition of the receipt of two or more antipsychotic drugs in parallel for a period of more than one month. Aim Antipsychotic prescribing was audited in two sites of Pennine Care NHS Trust (Oldham and Stockport) prior to the use of a prescribing intervention designed to reduce levels of combination antipsychotic prescribing in one of the sites (Oldham). Antipsychotic prescribing was then re-audited in both sites, with levels of combination prescribing being compared to pre-intervention levels and post-intervention levels in the site where the intervention did not take place (Stockport). Method Randomisation was carried out by an independent statistician, resulting in the Royal Oldham Hospital, Pennine Care NHS Trust, being randomised to receive the prescribing intervention and Stepping Hill Hospital, Stockport, also part of Pennine Care NHS Trust, being randomised to be the control site. The design of the prescribing intervention was informed by work on a systematic review looking at previous studies which had attempted to change mental health clinicians prescribing behaviour. This pointed to a multifaceted approach being more effective in changing prescribing practices and that effective methods included a combination of audit and feedback, the use of opinion leaders, educational outreach, and the use of reminders. The prescribing intervention comprised two main parts: firstly, a talk on evidencebased antipsychotic prescribing by an opinion leader was followed by an individual visit, which comprised an educational package and feedback of audit findings and secondly, a reminder system was used to alert clinicians to current cases of combination and high dose antipsychotic prescribing. Further details of the design of the prescribing intervention are available on request. 13

Power calculation & sample size A power calculation indicated that, with significance set at 0.05, 210 patients in each site would be sufficient to detect a reduction in rates of combination antipsychotic prescribing from 20% to 10%, with 80% power. Inflating this figure by 10% in each group to account for confounders meant that a minimum of 231 patients were required in each group. 14

Pre-Intervention Audit: Antipsychotic Prescribing Rates The population covered by the Royal Oldham Hospital is approximately 250,000; that covered by Stepping Hill Hospital, Stockport is approximately 350,000. Audit samples for the two sites were derived from the CPA (Care Programme Approach) Register. Following the removal of patients over the age of 65 years at the start of the intervention period plus a number of duplicate listings, there were 436 patients on the Oldham site register and 438 patients on the Stockport site register. The Oldham audit sample comprised 244 patients and the Stockport audit sample 248 patients. These two samples were comparable with the pool of available patients in each site (and therefore a representative sample) in addition to being similar to each other in terms of available demographic variables (see Table 1). Table 1: Pre-Intervention Audit: audit sample vs. overall population Age (years) Gender Oldham (Intervention site) Sample N=244 Overall pop. N=436 Sample N=248 Stockport (Control site) Overall pop. N=438 Mean (SD) 43.15 (11.54) 42.94 (11.82) 43.39 (11.08) 44.76 (11.23) Median 42.47 42.28 42.38 43.91 Range 19.52 64.30 19.52 64.81 19.16 63.77 19.16 64.86 Male (%) 156 (64%) 275 (63%) 159 (64%) 288 (66%) The pre-intervention audit measured antipsychotic prescribing prior to the start of the intervention period (i.e. before June 2006). 15

Table 2: Pre-Intervention Audit: characteristics of samples Ethnicity Oldham (Intervention site) N=244 Stockport (Control site) N=248 White 114 (47%) 157 (63%) Pakistani 20 (8%) 3 (1%) Bangladeshi 14 (6%) 1 Asian 7 (3%) 1 Afro-Caribbean 4 (2%) 0 Length of illness (years) Setting Indian 2 2 Caribbean 2 0 Irish 0 2 Mixed Race 1 1 Chinese 1 2 Kenyan 1 0 Jamaican 1 0 Cambodian 1 0 Iraqi 0 1 NK 76 (31%) 78 (32%) Mean (SD) 13.6 (8.39) 12.1 (9.09) Median/ Range 12/ 1-39 9/ 1-39 Inpatient 14 (6%) 17 (7%) Outpatient 230 (94%) 231 (93%) The majority of the two audit samples were white, more so in the Stockport (control) site and the majority were treated as outpatients. There was a wide range of lengths of illness in both sites (see Table 2). 16

Antipsychotic monotherapy prescribing Oldham (Intervention) Site Eight patients in the Oldham sample were not taking any antipsychotic drug treatment at the time of the audit. Drugs prescribed to patients treated with monotherapy in the Oldham site are listed in Table 3. Olanzapine was the oral drug prescribed to most patients and flupenthixol the depot most often prescribed. Table 3: Oldham (Intervention) Site: antipsychotic drugs prescribed to monotherapy group Antipsychotic N Mean Dose Median Dose Dose Range Amisulpride 4 463 mg 475 mg 200 700 mg Aripiprazole 4 21 mg 20 mg 15 30 mg Clozapine 34 417 mg 400 mg 200 650 mg Olanzapine 38 12 mg 10 mg 5 30 mg Quetiapine 8 244 mg 250 mg 50 400 mg Risperidone oral 25 4 mg 3 mg 1 12 mg Risperidone consta 13 37.5 2/52 37.5 2/52 25 2/52 50 2/52 Chlorpromazine 7 171 mg 100 mg 50 400 mg Flupenthixol dec. 30 155 5/52 110 4/52 20 6/52 150 2/52 Fluphenazine dec. 12 80 5/52 25 2/52 12.5 4/52 100 2/52 Haloperidol dec. 2 140 4/52 140 4/52 75 4/52 200 4/52 Pipothiazine palm. 2 100 4/52 100 4/52 50 4/52 150 4/52 Sulpiride 2 650 mg 650 mg 500 800 mg Trifluoperazine 1 10 mg -------- -------- Zuclopenthixol oral 1 100 mg -------- -------- Zuclopenthixol dec. 6 280 4/52 196 4/52 60 2/52 400 2/52 17

Stockport (Control) Site Seven of the sample in the Stockport audit were not taking any antipsychotic drug treatment. Drugs prescribed to patients treated with antipsychotic monotherapy are listed in Table 4. Clozapine was the oral drug prescribed to most patients on monotherapy in this site but flupenthixol was again the depot most often prescribed. Table 4: Stockport (Control) Site: antipsychotics prescribed to monotherapy group Antipsychotic N Mean Dose Median Dose Dose Range Amisulpride 12 683 mg 700 mg 400 1200 mg Aripiprazole 13 15 mg 15 mg 10 30 mg Clozapine 51 445 mg 450 mg 150 900 mg Olanzapine 44 15 mg 15 mg 5 30 mg Quetiapine 11 539 mg 600 mg 25 800 mg Risperidone oral 21 6 mg 5 mg 1 12 mg Risperidone consta 13 37.5 2/52 37.5 2/52 25 2/52 50 2/52 Chlorpromazine 1 50 mg -------- -------- Flupenthixol oral 1 3 mg -------- -------- Flupenthixol dec. 11 75 2/52 60 2/52 40 2/52 200 2/52 Fluphenazine dec. 5 155 5/52 50 2/52 50 3/52 125 2/52 Haloperidol oral 1 10 mg -------- -------- Haloperidol dec. 3 40 2/52 30 2/52 50 4/52 125 4/52 Pipothiazine palm. 4 30 2/52 25 2/52 25 4/52 50 2/52 Promazine 3 67 mg 50 mg 50 100 mg Sulpiride 1 400 mg -------- -------- Trifluoperazine 2 3.5 mg 3.5 mg 2 5 mg Zuclopenthixol oral 1 30 mg -------- -------- Zuclopenthixol dec 9 130 1/52 100 1/52 200 3/52 250 1/52 18

Combination antipsychotic prescribing Oldham (Intervention) Site Patients receiving treatment with antipsychotic drugs in combination comprised 22% of the Oldham sample (53 patients). Two patients had received such treatment for less than one month and four patients were treated with oral risperidone and injectable risperidone together; patients were not defined as receiving combination therapy if they were treated with the same antipsychotic drug via different delivery routes.. Prescribed combinations are listed in Table 5. Four of the co-prescribed patients were receiving three antipsychotic drugs together. The most common combination was olanzapine together with flupenthixol depot. The majority of co-prescribed patients (51%) were treated with an oral SGA (second generation antipsychotic, or atypical) together with a depot FGA (first generation antipsychotic, or conventional). Most of this group (85%) were treated with olanzapine together with an FGA depot. A further 15% of co-prescribed patients were treated with an FGA depot (mostly flupenthixol) together with an oral FGA; 11% with an oral SGA and an oral FGA; 11% with two oral SGAs (three olanzapine with another SGA and three clozapine plus a second SGA) and the four patients taking three antipsychotics were on olanzapine taken together with an FGA depot and an oral FGA (see figure 1). 19

Figure 1: Pre-Intervention pattern of co-prescribing: Oldham patients (N) 30 25 20 15 10 5 0 SGA oral & FGA depot FGA depot & FGA oral SGA oral & SGA oral SGA oral & FGA oral FGA oral & FGA oral 3 AP drugs 20

Table 5: Oldham (Intervention) Site: antipsychotic drugs co-prescribed SGA oral + FGA Depot FGA Depot + FGA Oral Olanzapine 30 + flupenthixol 30 2/52 Flupenthixol 80 1/52 + chlorpromazine 300 Olanzapine 25 + flupenthixol 40 2/52 Flupenthixol 150 2/52 + chlorpromazine 100 Olanzapine 20 + flupenthixol 150 2/52 Flupenthixol 100 2/52 + chlorpromazine 100 Olanzapine 20 + flupenthixol 100 2/52 Flupenthixol 50 2/52 + promazine 100 Olanzapine 20 + flupenthixol 60 2/52 Flupenthixol 50 2/52 + promazine 50 Olanzapine 20 + flupenthixol 20 2/52 Flupenthixol 30 2/52 + sulpiride 400 Olanzapine 15 + flupenthixol 100 2/52 Flupenthixol 37.5 2/52 + haloperidol 5 Olanzapine 10 + flupenthixol 200 1/52 Fluphenazine 25 3/52 + chlorpromazine 150 Olanzapine 10 + flupenthixol 100 2/52 SGA oral + SGA oral Olanzapine 10 + flupenthixol 60 2/52 Olanzapine 20 + amisulpride 400 Olanzapine 10 + flupenthixol 40 2/52 Olanzapine 20 + amisulpride 200 Olanzapine 10 + flupenthixol 20 2/52 Olanzapine 20 + aripiprazole 10 Olanzapine 5 + flupenthixol 160 2/52 Clozapine 600 + risperidone 2 Olanzapine 5 + flupenthixol 80 1/52 Clozapine 750 + risperidone 4 Olanzapine 5 + flupenthixol 40 2/52 Clozapine 400 + amisulpride 200 Olanzapine 5 + flupenthixol 50 4/52 SGA oral + FGA oral Olanzapine 20 + fluphenazine 40 4/52 Clozapine 900 + sulpiride 800 Olanzapine 15 + fluphenazine 100 4/52 Clozapine 600 + sulpiride 600 Olanzapine 40 + zuclopenthixol 100 2/52 Clozapine 400 + promazine 200 Olanzapine 15 + zuclopenthixol 300 2/52 Olanzapine 20 + chlorpromazine 150 Olanzapine 10 + zuclopenthixol 600 2/52 Olanzapine 15 + chlorpromazine 250 Olanzapine 5 + zuclopenthixol 200 2/52 Amisulpride 400 + promazine 75 Olanzapine 15 + pipothiazine palm. 60 2/52 Risperidone 2 + chlorpromazine 100 Risperidone 6 + fluphenazine 100 1/52 FGA oral + FGA oral Risperidone 2 + fluphenazine 50 4/52 Sulpiride 1000 + chlorpromazine 200 Quetiapine 600 + flupenthixol 100 2/52 3 antipsychotic drugs Quetiapine 250 + flupenthixol 30 2/52 Olanzapine 35 + flupenthixol 100 2/52 + chlorpromazine 250 Olanzapine 20 + flupenthixol 60 2/52 + haloperidol 30 Olanzapine 20 + flupenthixol 80 1/52 + chlorpromazine 50 Olanzapine 10 + fluphenazine 37.5 2/52 + chlorpromazine 50 21

Stockport (Control) Site In the Stockport site, patients receiving combination treatment comprised 16% of the sample (39 patients). Two patients were taking a second antipsychotic drug listed as prn, one patient had received combination treatment for less than one month and two patients were treated with oral risperidone and injectable risperidone together: these patients were not defined as receiving combination treatment. Combinations of drugs in this sample are listed in Table 6. One patient was taking three antipsychotics concurrently. The most common combination was olanzapine and flupenthixol depot in this site also. The majority of patients receiving combination treatment were receiving an oral SGA drug together with a depot FGA (49% of coprescribed patients). The majority (58%) of this group were treated with olanzapine together with an FGA depot. A further 23% of those co-prescribed were treated with an FGA depot together with an oral FGA; 15% received two oral SGAs (four clozapine with a second SGA and two olanzapine plus a second SGA); 10% were taking an oral SGA together with an oral FGA and the patient on three antipsychotics was taking an FGA depot and two oral FGAs combined (see figure 2). Figure. 2: Pre-Intervention pattern of co-prescribing: Stockport patients (N) 20 18 16 14 12 10 8 6 4 2 0 SGA oral & FGA depot FGA depot & FGA oral SGA oral & SGA oral SGA oral & FGA oral 3 AP drugs 22

Table 6: Stockport (Control) Site: antipsychotic drugs co-prescribed SGA oral + FGA Depot FGA Depot + FGA Oral Olanzapine 20 + flupenthixol 70 2/52 Flupenthixol 100 2/52 + chlorpromazine 50 Olanzapine 20 + flupenthixol 80 3/52 Flupenthixol 40 3/52 + chlorpromazine 350 Olanzapine 20 + flupenthixol 20 2/52 Flupenthixol 100 1/52 + trifluoperazine 5 Olanzapine 20 + flupenthixol 25 3/52 Flupenthixol 50 2/52 + trifluoperazine 15 Olanzapine 10 + flupenthixol 30 2/52 Fluphenazine 75 1/52 + trifluoperazine 15 Olanzapine 5 + flupenthixol 40 2/52 Fluphenazine 25 2/52 + haloperidol 5 Olanzapine 5 + flupenthixol 20 2/52 Pipo palm. 150 2/52 + chlorpromazine 300 Olanzapine 20 + fluphenazine 50 4/52 Pipo palm. 75 4/52 + promazine 150 Olanzapine 10 + fluphenazine 37.5 6/52 Zuclopenthixol 500 2/52 + chlorpromazine 300 Olanzapine 5 + fluphenazine 25 1/52 SGA oral + SGA oral Olanzapine 15 + zuclopenthixol 200 2/52 Clozapine 475 + amisulpride 800 Risperidone 6 + flupenthixol 60 4/52 Clozapine 450 + amisulpride 400 Risperidone 8 + fluphenazine 12.5 3/52 Clozapine 700 + quetiapine 400 Risperidone 3 + fluphenazine 50 1/52 Clozapine 600 + quetiapine 400 Risperidone 8 + zuclopenthixol 200 2/52 Olanzapine 20 + aripiprazole 5 Quetiapine 700 + flupenthixol 50 2/52 Olanzapine 10 + amisulpride 800 Quetiapine 600 + flupenthixol 250 3/52 SGA oral + FGA oral Amisulpride 200 + flupenthixol 100 3/52 Olanzapine 20 + flupenthixol 12 Aripiprazole 10 + zuclopenthixol 300 2/52 Olanzapine 5 + haloperidol 45 3 antipsychotic drugs Olanzapine 2.5 + fluphenazine 10 Flupenthixol 40 2/52 + Trifluoperazine 15 + Thioridazine 50 Risperidone 6 + promazine 75 23

High Dose antipsychotic prescribing Oldham (Intervention) Site Eleven of the Oldham sample (5%) were treated with a high dose of over 1000 mg chlorpromazine equivalents (CPZEq). All but one of these were receiving combination treatment and three patients were taking three antipsychotic drugs concurrently (see Table 7). Table 7: Oldham (Intervention) Site: high dose prescribing (CPZEq) Drug 1 Drug 2 Drug 3 poly 1 Olanzapine 20 mg Flupenthixol 150 2/52 2 Olanzapine 10 mg Flupenthixol 200 1/52 3 Clozapine 750 mg Risperidone 4 mg 4 Clozapine 900 mg Sulpiride 800 mg 5 Risperidone 6 mg Fluphenazine 100 1/52 6 Quetiapine 600 mg Flupenthixol 100 2/52 7 Flupenthixol 80 1/52 Chlorpromazine 300 mg 8 Olanzapine 35 mg Flupenthixol 100 2/52 Chlorpromazine 250 mg 9 Olanzapine 20 mg Flupenthixol 80 1/52 Chlorpromazine 50 mg 10 Olanzapine 20 mg Flupenthixol 60 2/52 Haloperidol 30 mg 11 Risperidone 12 mg Risperidone 50 2/52 X 24

Stockport (Control) Site Thirteen of the Stockport sample (5%) were treated with a high dose (>1000 mg CPZEq). Two-thirds of these (nine patients) received combination treatment (see Table 8). Table 8: Stockport (Control) Site: high dose prescribing (CPZEq) Drug 1 Drug 2 poly 1 Amisulpride 1200 mg X 2 Quetiapine 800 mg X 3 Quetiapine 800 mg X 4 Quetiapine 800 mg X 5 Clozapine 700 mg Quetiapine 400 mg 6 Clozapine 600 mg Quetiapine 400 mg 7 Clozapine 475 mg Amisulpride 800 mg 8 Quetiapine 700 mg Flupenthixol 50 2/52 9 Quetiapine 600 mg Flupenthixol 250 3/52 10 Olanzapine 5 mg Haloperidol 45 mg 11 Flupenthixol 100 1/52 Trifluoperazine 5 mg 12 Fluphenazine 75 1/52 Trifluoperazine 15 mg 13 Pipothiazine palm. 150 2/52 Chlorpromazine 300 mg 25

Table 9 shows chlorpromazine equivalent (CPZEq) doses for patients receiving combination treatment or monotherapy. CPZEq doses of co-prescribed patients were higher than those treated with a single antipsychotic drug in both sites (p<0.001). In the Oldham (intervention site) 91% of patients receiving a high dose were on combination treatment; in the Stockport (control) site this figure was 69%. Table 9: Pre-Intervention Prescribing Audit: CPZEq doses CPZEq Dose Oldham (Intervention) site Monotherapy Group N=191 Co-prescribed Group N=53 Monotherapy Group N=209 Stockport (Control) site Co-prescribed Group N=39 Mean (SD) 311.01 (188.06) 720.08 (416.68) 386 (238.13) 707 (374.65) Median 300.00 600.00 341.5 550 Range 20 1400 200 2200 33-1200 200-1633 As there is a debate as to which method to best use to convert drug doses, these were also converted into percentage of maximum recommended dose for each antipsychotic drug (%MaxBNF Dose) listed in the British National Formulary (BNF, 2006). 26

Oldham (Intervention) Site The use of this definition led to 22 patients (9%) being defined as receiving a high dose in the Oldham site. As can be seen in Table 10 this was mainly because of the inclusion of patients receiving a daily dose of over 20 mg of olanzapine in the high dose group. The majority of the high dose group were, again receiving combination treatment and three of the group were prescribed more than two antipsychotics concurrently. Table 10: Oldham (Intervention) Site: high doses (>100% Max BNF Dose) Drug 1 Drug 2 Drug 3 poly 1 Olanzapine 30 mg X 2 Risperidone 3 mg Risperidone 50 2/52 X 3 Risperidone 12 mg Risperidone 50 2/52 X 4 Olanzapine 30 mg Flupenthixol 30 2/52 5 Olanzapine 25 mg Flupenthixol 40 2/52 6 Olanzapine 20 mg Flupenthixol 20 2/52 7 Olanzapine 20 mg Flupenthixol 100 2/52 8 Olanzapine 20 mg Flupenthixol 60 2/52 9 Olanzapine 20 mg Flupenthixol 150 2/52 10 Olanzapine 20 mg Amisulpride 400 mg 11 Olanzapine 20 mg Amisulpride 200 mg 12 Olanzapine 20 mg Aripiprazole 10 mg 13 Olanzapine 20 mg Fluphenazine 40 4/52 14 Olanzapine 40 mg Zuclopenthixol 100 2/52 15 Olanzapine 15 mg Pipothiazine palm. 60 2/52 16 Olanzapine 20 mg Chlorpromazine 150 mg 17 Clozapine 750 mg Risperidone 4 mg 18 Clozapine 900 mg Sulpiride 800 mg 19 Risperidone 6 mg Fluphenazine 100 1/52 20 Olanzapine 20 mg Flupenthixol 60 2/52 Haloperidol 30 mg 21 Olanzapine 35 mg Flupenthixol 100 2/52 Chlorpromazine 250 mg 22 Olanzapine 20 mg Flupenthixol 80 1/52 Chlorpromazine 50 mg 27

Stockport (Control) Site The use of the percentage of maximum recommended BNF dose (%MaxBNF) dose conversion led to 26 patients (10%) in the Stockport site being categorised as receiving high dose treatment (see Table 11). Table 11: Stockport (Control) Site: high doses (>100% Max BNF Dose) Drug 1 Drug 2 poly 1 Olanzapine 30 mg X 2 Olanzapine 25 mg X 3 Olanzapine 25 mg X 4 Olanzapine 25 mg X 5 Quetiapine 800 mg X 6 Quetiapine 800 mg X 7 Quetiapine 800 mg X 8 Risperidone 50 2/52 Risperidone 1 mg X 9 Risperidone 50 2/52 Promazine 50 mg prn X 10 Fluphenazine 125 2/52 Chlorpromazine 50 mg prn X 11 Olanzapine 20 mg Flupenthixol 70 2/52 12 Olanzapine 20 mg Flupenthixol 80 3/52 13 Olanzapine 20 mg Flupenthixol 20 2/52 14 Olanzapine 20 mg Flupenthixol 25 3/52 15 Olanzapine 20 mg Fluphenazine 50 4/52 16 Olanzapine 10 mg Amisulpride 800 mg 17 Olanzapine 20 mg Aripiprazole 5 mg 18 Clozapine 700 mg Quetiapine 400 mg 19 Clozapine 600 mg Quetiapine 400 mg 20 Clozapine 475 mg Amisulpride 800 mg 21 Quetiapine 600 mg Flupenthixol 250 3/52 22 Risperidone 3 mg Fluphenazine 50 1/52 23 Olanzapine 20 mg Flupenthixol 12 mg 24 Olanzapine 5 mg Haloperidol 45 mg 25 Pipothiazine palm. 150 2/52 Chlorpromazine 300 mg 26 Fluphenazine 75 1/52 Trifluoperazine 15 mg 28

Table 12 sets out the %MaxBNF doses for patients receiving combination treatment or monotherapy, showing that %MaxBNF doses of co-prescribed patients were higher than those treated with a single antipsychotic drug in both sites (p=0.001). In the Oldham (intervention) site 86% of patients receiving a high dose, using this definition, were on combination treatment; in the Stockport (control) site this figure was 62%. Table 12: Pre-Intervention Prescribing Audit: %MaxBNF doses %MaxBNF Dose Oldham (Intervention) site Monotherapy Group N=191 Co-prescribed Group N=53 Monotherapy Group N=209 Stockport (Control) site Co-prescribed Group N=39 Mean (SD) 39% (30.33) 84% (50.32) 53% (30.51) 82% (46.44) Median 33% 87.5% 50% 75% Range 1% - 175% 12.5% - 212.5% 3% 150% 5% 180% 29

Summary: Pre-Intervention Prescribing Audit Oldham (Intervention) Site Out of a sample of 244 patients, 53 patients (22%) were treated with combination antipsychotic treatment in the Oldham site. Four of these were taking three drugs concurrently. The most used combination was olanzapine together with flupenthixol depot. The use of the CPZEq dose conversion gave a 5% rate of high dose prescribing, whereas the use of the %MaxBNF dose conversion gave a higher rate of 9%. Treatment with combination therapy was associated with significantly higher dose prescribing regardless of the definition used, with between 86% and 91% of high dose prescribing made up of combination treatment. Stockport (Control) Site Of a sample of 248 patients, 39 patients (16%) in the Stockport site were treated with combination prescribing. The combination used most often was also olanzapine with flupenthixol depot. The CPZEq dose conversion gave a 5% rate of high dose prescribing, whereas the %MaxBNF dose conversion gave a higher rate of 10%. Treatment with combination therapy was again associated with significantly higher dose prescribing regardless of the definition used, with between 62% and 69% of high dose prescribing made up of combination treatment. 30

Prescribing Intervention A prescribing intervention was delivered to all mental health clinicians working in Adult Psychiatry at the Royal Oldham Hospital, with the aim of reducing rates of combination antipsychotic prescribing. The period covered by the intervention began in June 2006 and ended in March 2007. Details of the intervention are available on request. 31

Post-Intervention Antipsychotic Prescribing Audit Post intervention antipsychotic prescribing rates were measured in the original samples of 244 patients in the Oldham (intervention) site and 248 patients in the Stockport (control) site. 32

Monotherapy prescribing Oldham (Intervention) Site Following the end of the intervention period ten patients were not receiving any antipsychotic drug treatment in the Oldham site. Olanzapine was again the SGA drug prescribed alone to most patients and flupenthixol the depot drug prescribed singly to most patients. Table 13 sets out drugs prescribed to the group as monotherapy. Table 13: Oldham (Intervention) Site: antipsychotic drugs prescribed as monotherapy Antipsychotic Drug N Mean Dose Median Dose Dose Range Amisulpride 4 400 mg 350 mg 200 700 mg Aripiprazole 5 21 mg 20 mg 15 30 mg Clozapine 30 423 mg 400 mg 200 650 mg Olanzapine 38 12 mg 10 mg 3.75 27.5 mg Quetiapine 6 258 mg 250 mg 150 400 mg Risperidone oral 26 4 mg 4 mg 1 12 mg Risperidone consta 15 37.5 2/52 37.5 2/52 25 2/52 50 2/52 Chlorpromazine 6 185 mg 100 mg 25 350 mg Flupenthixol dec. 37 140 5/52 50 2/52 20 6/52 150 2/52 Fluphenazine dec. 11 37.5 2/52 25 2/52 12.5 8/52 100 2/52 Haloperidol oral 1 10 mg -------- -------- Haloperidol dec. 2 150 4/52 150 4/52 100 4/52 200 4/52 Pipothiazine palm. 2 50 2/52 50 2/52 50 4/52 150 4/52 Sulpiride 1 1200 mg -------- -------- Trifluoperazine 1 4 mg -------- -------- Zuclopenthixol oral 1 100 mg -------- -------- Zuclopenthixol dec. 6 590 5/52 200 2/52 100 3/52 600 2/52 33

Stockport (Control) Site Eleven patients were taking no antipsychotic drug treatment following the intervention in this site. Clozapine was the oral drug prescribed to most patients on monotherapy and flupenthixol the depot most often prescribed (see Table 14 for further details). Table 14: Stockport (Control) Site: antipsychotic drugs prescribed as monotherapy Antipsychotic Drug N Mean Dose Median Dose Dose Range Amisulpride 11 655 mg 700 mg 200 1200 mg Aripiprazole 10 17 mg 15 mg 10 30 mg Clozapine 53 445 mg 438 mg 150 900 mg Olanzapine 39 16 mg 15 mg 2.5 30 mg Quetiapine 9 606 mg 700 mg 50 950 mg Risperidone oral 23 6 mg 6 mg 1 12 mg Risperidone consta 18 37.2 2/52 37.5 2/52 25 2/52 50 2/52 Chlorpromazine 1 50 mg -------- -------- Flupenthixol oral 2 4.5 mg 4.5 mg 3 6 mg Flupenthixol dec. 14 75 2/52 40 2/52 25 4/52 200 2/52 Fluphenazine dec. 4 140 5/52 90 5/52 37.5 3/52 125 2/52 Haloperidol oral 3 5 mg 5 mg 1 10 mg Haloperidol dec. 3 85 5/52 25 2/52 25 2/52 100 4/52 Pipothiazine palm. 4 110 5/52 50 2/52 50 4/52 100 4/52 Promazine 3 67 mg 75 mg 25 100 mg Sulpiride 1 400 mg -------- -------- Trifluoperazine 2 3.5 mg 3.5 mg 2 5 mg Zuclopenthixol oral 2 37.5 mg 37.5 mg 25 50 mg Zuclopenthixol depot 10 286 2/52 300 2/52 200 3/52 400 2/52 34

Combination Antipsychotic Prescribing Oldham (Intervention) Site Patients receiving treatment with combination therapy following the intervention, comprised 20% of the sample in the Oldham site (50 patients). Two patients had received such treatment for less than one month and a further five patients were treated with oral risperidone and injectable risperidone together; not defined as coprescribing in this study. Combinations prescribed in the intervention site are listed in Table 15. Four patients were again treated with three antipsychotic drugs. The most common combination remained olanzapine together with flupenthixol depot. The majority of co-prescribed patients were treated with an SGA oral drug together with a FGA depot (44% of combination-treated patients). A further 20% of co-prescribed patients received two oral SGAs (five olanzapine with another SGA and five clozapine plus a second SGA); 16% were treated with an FGA depot (mainly flupenthixol) together with an oral FGA; 10% were taking an oral SGA together with an oral FGA and three of the four taking three antipsychotic drugs comprised olanzapine together with an FGA depot and an oral FGA (see figure 3). 35

Figure 3: Post-Intervention pattern of co-prescribing: Oldham 25 patients (N) 20 15 10 5 0 SGA oral & FGA depot FGA depot & FGA oral SGA oral & SGA oral SGA oral & FGA oral SGA oral & SGA depot 3 AP drugs 36

Table 15: Oldham (Intervention) Site: antipsychotic drugs co-prescribed SGA oral + FGA Depot SGA oral + SGA oral Olanzapine 30 + flupenthixol 30 2/52 Clozapine 700 + amisulpride 400 Olanzapine 20 + flupenthixol 150 2/52 Clozapine 600 + amisulpride 800 Olanzapine 20 + flupenthixol 60 2/52 Clozapine 300 + amisulpride dose NK Olanzapine 20 + flupenthixol 40 2/52 Clozapine 700 + risperidone 8 Olanzapine 20 + flupenthixol 20 2/52 Clozapine 600 + risperidone 4 Olanzapine 15 + flupenthixol 150 2/52 Olanzapine 25 + amisulpride 100 Olanzapine 10 + flupenthixol 100 1/52 Olanzapine 20 + amisulpride 400 Olanzapine 5 + flupenthixol 200 1/52 Olanzapine 20 + amisulpride 50 Olanzapine 5 + flupenthixol 80 1/52 Olanzapine 15 + amisulpride 400 Olanzapine 5 + flupenthixol 160 2/52 Olanzapine 15 + aripiprazole 10 Olanzapine 2.5 + flupenthixol 50 4/52 SGA oral + FGA oral Olanzapine 20 + fluphenazine 40 4/52 Clozapine 600 + sulpiride 600 Olanzapine 15 + fluphenazine 100 4/52 Clozapine 400 + promazine 200 Olanzapine 10 + fluphenazine 37.5 2/52 Olanzapine 20 + chlorpromazine 150 Olanzapine 40 + zuclopenthixol 100 2/52 Risperidone 2 + chlorpromazine 100 Olanzapine 20 + zuclopenthixol 300 2/52 Amisulpride 400 + Promazine 75 Olanzapine 10 + zuclopenthixol 200 2/52 SGA oral + SGA depot Olanzapine 15 + pipothiazine palm. 60 2/52 Olanzapine 15 + risperidone 50 2/52 Quetiapine 600 + flupenthixol 100 2/52 3 antipsychotic drugs Quetiapine 250 + flupenthixol 20 2/52 Clozapine 700 + haloperidol 2 + sulpiride 400 Risperidone 6 + fluphenazine 100 1/52 Olanzapine 20 + flupenthixol 80 1/52 + chlorpromazine 50 Risperidone 2 + fluphenazine 50 3/52 Olanzapine 35 + chlorpromazine 250 + flupenthixol 100 2/52 FGA Depot + FGA Oral Olanzapine 20 + flupenthixol 150 2/52 + haloperidol 30 Flupenthixol 80 1/52 + chlorpromazine 300 Flupenthixol 150 2/52 + chlorpromazine 100 Flupenthixol 100 2/52 + chlorpromazine 100 Flupenthixol 40 3/52 + chlorpromazine 50 Flupenthixol 30 2/52 + sulpiride 400 Flupenthixol 50 2/52 + promazine 100 Flupenthixol 50 2/52 + promazine 50 Fluphenazine 25 3/52 + chlorpromazine 37

Stockport (Control) Site Those receiving treatment with antipsychotics in combination following the intervention comprised 14% of the Stockport site sample (35 patients). Four patients received a second antipsychotic listed as prn, one patient had received combination treatment for less than one month, three patients were treated with oral risperidone and injectable risperidone together and one patient was taking oral flupenthixol together with a flupenthixol depot: these patients were not defined as receiving combination treatment. Combinations prescribed in the control site are listed in Table 16. The most common combination was olanzapine and flupenthixol depot together. The majority of coprescribed patients (40%) were still treated with a SGA oral together with a FGA depot. A further 37% were treated with an oral FGA together with a FGA depot; 11% received two oral SGAs; 9% were taking an oral SGA together with an oral FGA and one patient was taking a combination of an SGA depot and an oral FGA (see figure 4). Figure 4: Post-Intervention pattern of co-prescribing: Stockport patient (N) 16 14 12 10 8 6 4 2 0 SGA oral & FGA depot FGA depot & FGA oral SGA oral & SGA oral SGA oral & FGA oral SGA depot & FGA oral 38

Table 16: Stockport (Control) Site: antipsychotic drugs co-prescribed FGA Depot + FGA Oral SGA oral + FGA Depot Flupenthixol 100 2/52 + chlorpromazine 50 Olanzapine 20 + flupenthixol 70 2/52 Flupenthixol 100 3/52 + chlorpromazine 110 Olanzapine 20 + flupenthixol 50 4/52 Flupenthixol 40 3/52 + chlorpromazine 350 Olanzapine 20 + flupenthixol 20 2/52 Flupenthixol 100 1/52 + trifluoperazine 5 Olanzapine 10 + flupenthixol 40 3/52 Flupenthixol 50 2/52 + trifluoperazine 15 Olanzapine 5 + flupenthixol 20 2/52 Flupenthixol 40 2/52 + trifluoperazine 15 Olanzapine 20 + fluphenazine 50 4/52 Flupenthixol 40 1/52 + promazine 100 Olanzapine 5 + fluphenazine 25 1/52 Fluphenazine 37.5 2/52 + haloperidol 7 Olanzapine 5 + fluphenazine 37.5 6/52 Fluphenazine 75 1/52 + trifluoperazine 15 Olanzapine 5 + zuclopenthixol 200 2/52 Fluphenazine 75 2/52 + promazine 50 Risperidone 8 + fluphenazine 12.5 3/52 Pipothiazine palm. 50 2/52 + promazine 50 Risperidone 4 + fluphenazine 50 1/52 Pipothiazine palm. 75 4/52 + promazine 150 Risperidone 6 + flupenthixol 40 4/52 Zuclopenthixol 500 2/52 + chlorpromazine 300 Quetiapine 600 + flupenthixol 250 3/52 SGA oral + SGA oral Quetiapine 200 + pipo palm. 150 2/52 Clozapine 575 + amisulpride 800 SGA oral + FGA oral Clozapine 700 + quetiapine 400 Quetiapine 800 + haloperidol 20 Olanzapine 15 + amisulpride 800 Quetiapine 750 + haloperidol 6 Olanzapine 10 + amisulpride 1200 Risperidone 6 + Promazine 75 SGA Depot + FGA oral Risperidone 37.5 2/52 + Promazine 100 39

High Dose antipsychotic prescribing Oldham (Intervention) Site Fourteen patients in the Oldham site (6%) were treated with a defined high dose (>1000 mg CPZEq) at follow-up. All but one of these were receiving combination treatment and three of the sample were taking three antipsychotics concurrently (see Table 17). Table 17: Oldham (Intervention) Site: high dose prescribing (CPZEq) Drug 1 Drug 2 Drug 3 poly 1 Risperidone 12 mg Risperidone 50 2/52 X 2 Olanzapine 20 mg Flupenthixol 150 2/52 3 Olanzapine 15 mg Flupenthixol 150 2/52 4 Olanzapine 10 mg Flupenthixol 100 1/52 5 Olanzapine 5 mg Flupenthixol 200 1/52 6 Clozapine 700 mg Amisulpride 400 mg 7 Clozapine 600 mg Amisulpride 800 mg 8 Clozapine 700 mg Risperidone 6 mg 9 Quetiapine 600 mg Flupenthixol 100 2/52 10 Risperidone 6 mg Fluphenazine 100 1/52 11 Flupenthixol 80 1/52 Chlorpromazine 300 mg 12 Olanzapine 35 mg Flupenthixol 100 2/52 Chlorpromazine 250 mg 13 Olanzapine 20 mg Flupenthixol 80 1/52 Chlorpromazine 50 mg 14 Olanzapine 20 mg Flupenthixol 150 2/52 Haloperidol 30 mg 40

Stockport (Control) Site Fourteen of the Stockport sample (6%) were treated with a defined high dose (>1000 mg CPZEq) at follow-up. Over two-thirds of these were receiving combination treatment (see Table 18). Table 18: Stockport (Control) Site: high dose prescribing (CPZEq) Drug 1 Drug 2 poly 1 Quetiapine 950 mg X 2 Quetiapine 800 mg X 3 Quetiapine 800 mg X 4 Amisulpride 1200 mg X 5 Olanzapine 15 mg Amisulpride 800 mg 6 Olanzapine 10 mg Amisulpride 1200 mg 7 Clozapine 575 mg Amisulpride 800 mg 8 Clozapine 700 mg Quetiapine 400 mg 9 Quetiapine 800 mg Haloperidol 20 mg 10 Quetiapine 750 mg Haloperidol 6 mg 11 Quetiapine 600 mg Flupenthixol 250 3/52 12 Quetiapine 200 mg Pipothiazine palm. 150 2/52 13 Flupenthixol 100 1/52 Trifluoperazine 5 mg 14 Fluphenazine 75 1/52 Trifluoperazine 15 mg 41

Table 19 shows CPZEq doses of monotherapy-treated patients and combinationtreated patients. The median CPZEq dose was again higher in the co-prescribed group compared with the monotherapy group in both sites (p<0.001). Receiving high dose treatment was associated with co-prescribing: in the Oldham (intervention) site 93% of high dose patients were receiving combination treatment; in the Stockport (control) site this figure was 71%. Table 19: Post-Intervention Prescribing: CPZEq doses CPZEq Dose Oldham (Intervention) site Monotherapy Group N=194 Co-prescribed Group N=50 Monotherapy Group N=213 Stockport (Control) site Co-prescribed Group N=35 Mean (SD) 317.54 (189.29) 782.33 (458.12) 399.09 (244.55) 716.52 (421.98) Median 300.00 666.67 400.00 550.00 Range 20.83 1400.00 175.0 2150.0 33.33 1266.67 183.33 1733.34 42

High Dose Antipsychotic Prescribing Oldham (Intervention) Site Twelve per cent of the Oldham site sample (29 patients) were defined as receiving a high dose at follow-up when these were converted into percentage of maximum BNF recommended dose. At least one drug taken by 72% in this group was olanzapine. The majority of this high dose group were, again, receiving combination treatment and four of this group were prescribed three antipsychotic drugs concurrently (see Table 20). 43

Table 20: Oldham (Intervention) Site: high doses (>100% Max BNF Dose) Drug 1 Drug 2 Drug 3 poly 1 Olanzapine 27.5 mg X 2 Risperidone 12 mg Risperidone consta 50 2/52 X 3 Risperidone 6 mg Risperidone consta 37.5 2/52 X 4 Risperidone 3 mg Risperidone consta 50 2/52 X 5 Olanzapine 30 mg Flupenthixol 30 2/52 6 Olanzapine 20 mg Flupenthixol 150 2/52 7 Olanzapine 20 mg Flupenthixol 60 2/52 8 Olanzapine 20 mg Flupenthixol 40 2/52 9 Olanzapine 20 mg Flupenthixol 20 2/52 10 Olanzapine 20 mg Fluphenazine 40 4/52 11 Olanzapine 15 mg Fluphenazine 100 4/52 12 Olanzapine 40 mg Zuclopenthixol 100 2/52 13 Olanzapine 20 mg Zuclopenthixol 300 2/52 14 Olanzapine 15 mg Pipothiazine palm. 60 2/52 15 Olanzapine 25 mg Amisulpride 100 mg 16 Olanzapine 20 mg Amisulpride 400 mg 17 Olanzapine 20 mg Amisulpride 50 mg 18 Olanzapine 15 mg Amisulpride 400 mg 19 Olanzapine 15 mg Aripiprazole 10 mg 20 Olanzapine 15 mg Risperidone consta 50 2/52 21 Olanzapine 20 mg Chlorpromazine 150 mg 22 Clozapine 700 mg Amisulpride 400 mg 23 Clozapine 600 mg Amisulpride 800 mg 24 Clozapine 700 mg Risperidone 8 mg 25 Risperidone 6 mg Fluphenazine 100 1/52 26 Olanzapine 35 mg Flupenthixol 100 2/52 Chlorpromazine 250 mg 27 Olanzapine 20 mg Flupenthixol 80 1/52 Chlorpromazine 50 mg 28 Olanzapine 20 mg Flupenthixol 150 2/52 Haloperidol 30 mg 29 Clozapine 700 mg Sulpiride 400 mg Haloperidol 2 mg 44

Stockport (Control) Site Using the %MaxBNF dose as the definition of high dose prescribing, 24 patients (10%) in the Stockport site were categorised as receiving a high dose following the intervention period (see Table 21). Table 21: Stockport (Control) Site: high doses (>100% Max BNF Dose) Drug 1 Drug 2 poly 1 Olanzapine 30 mg X 2 Olanzapine 30 mg X 3 Olanzapine 25 mg X 4 Olanzapine 25 mg X 5 Olanzapine 25 mg X 6 Quetiapine 950 mg X 7 Quetiapine 800 mg X 8 Quetiapine 800 mg X 9 Risperidone 1 mg Risperidone 50 2/52 X 10 Risperidone 50 2/52 Zuclopenthixol 50 mg prn X 11 Olanzapine 20 mg Flupenthixol 70 2/52 12 Olanzapine 20 mg Flupenthixol 50 4/52 13 Olanzapine 20 mg Flupenthixol 20 2/52 14 Olanzapine 20 mg Fluphenazine 50 4/52 15 Olanzapine 15 mg Amisulpride 800 mg 16 Olanzapine 10 mg Amisulpride 1200 mg 17 Quetiapine 200 mg Pipothiazine palm. 150 2/52 18 Quetiapine 600 mg Flupenthixol 250 3/52 19 Quetiapine 800 mg Haloperidol 20 mg 20 Quetiapine 750 mg Haloperidol 6 mg 21 Clozapine 575 mg Amisulpride 800 mg 22 Clozapine 700 mg Quetiapine 400 mg 23 Risperidone 4 mg Fluphenazine 50 1/52 24 Fluphenazine 75 1/52 Trifluoperazine 15 mg 45

Table 22 shows %MaxBNF doses for patients on monotherapy treatment and patients on combination treatment. The median %MaxBNF dose was again higher in the co-prescribed group compared with the monotherapy group in both sites (p=0.005). In the Oldham (intervention) site 86% of patients receiving a high dose were treated with combination therapy; in the Stockport (control) site this figure was 58%. Table 22: Post-Intervention Prescribing Audit: %MaxBNF doses %MaxBNF Dose Oldham (Intervention) site Monotherapy Group N=194 Co-prescribed Group N=50 Monotherapy Group N=213 Stockport (Control) site Co-prescribed Group N=35 Mean (SD) 41% (31.45) 93% (56.63) 53% (31.65) 79% (49.42) Median 36% 97% 50% 72% Range 1% - 175% 8% 237.5% 2% 150% 5% 177% 46