Schizophrenia in Greater Manchester: Audit

Transcription

1 S i G M A Schizophrenia in Greater Manchester: Audit SiGMA Schizophrenia in Greater Manchester: Audit Report Audit Co-ordinator/ Author of Report: Project Lead Applicants: Darragh Downey, Karen P Hayhurst: The University of Manchester Professor Shôn W Lewis: The University of Manchester Petra Brown: Manchester Mental Health & Social Care Trust

2 Table of Contents Page List of Tables 3 List of Figures 4 Executive Summary 6 Recommendations 10 Available Guidance 11 Introduction 13 Outline of Work 13 Greater Manchester Clozapine Prescribing Census 15 Primary care antipsychotic prescribing and expenditure across Greater Manchester England Primary Care Antipsychotic Prescribing 54 Combination and high dose antipsychotic prescribing 63 The impact of antipsychotic prescribing on resource use: the effect of treatment with long-acting injectable Risperidone (Risperdal Consta) on hospitalisation rates Development of a patient-rated brief side effect rating scale for use across care settings Dissemination 72 Acknowledgements 73 References 74 Appendices

3 List of Tables Table Page 1 Gtr Manchester Primary Care Antipsychotic Spend: comparison between PCTs 2 Gtr Manchester Primary Care Antipsychotic Prescribing: comparison between PCTs A1 Greater Manchester Clozapine Census: Raw Data 80 A2 Greater Manchester Clozapine Census: Population Adjusted Data 81 A3 Greater Manchester Clozapine Census: Population- & Need-Adjusted Data 82 A4 Greater Manchester Clozapine Census by Mental Health Trust 83 A5 England Antipsychotic Drug Expenditure ( thousands) 97 A6 England Antipsychotic Drugs: Items Dispensed (thousands) 101 A7 Factor analysis of all side effect scale items 105 3

4 List of Figures Fig. Page 1 Greater Manchester Clozapine Prescribing Clozapine Prescribing by District: Raw Data 19 3 Clozapine Prescribing by District: Population-Adjusted Data 20 4 Clozapine Prescribing by District: Population- & Need-Adjusted Data 21 5 Clozapine prescribing: Variation between districts 22 6 Clozapine prescribing by Greater Manchester Trusts: Raw Data 23 7 Clozapine prescribing by Trust: Population-Adjusted Data 24 8 Clozapine prescribing by Trust: Population- & Need- Adjusted Data 25 9 Clozapine prescribing: Variation between Trusts: Population- & Need- Adjusted Data Gtr Manchester Primary Care Total SGA Spend Gtr Manchester Primary Care Individual SGA Spend Gtr Manchester Primary Care SGA & FGA Spend / Gtr Manchester Primary Care Ratio of SGA to FGA Spend / Gtr Manchester Primary Care Spend: Depot FGA and Oral FGA /12 15 Gtr Manchester Primary Care Spend: Ratio of Oral FGA to depot FGA / Gtr Manchester Primary Care Individual SGA Spend / Gtr Manchester Primary Care Antipsychotic Spend Q2 2011/ Weighed prescribing costs of FGAs across Greater Manchester Weighed prescribing costs of SGAs across Greater Manchester National Spend on Antipsychotic Medication Q2 2011/ Gtr Manchester Primary Care Ratio of SGA to FGA Items Prescribed / Gtr Manchester Primary Care Ratio of SGA to FGA Items Prescribed /12 23 Gtr Manchester Primary Care Items Prescribed: Number of Oral FGA to Depot FGA prescribed /12 24 Gtr Manchester Primary Care Ratio of oral to depots FGAs prescribed /12 25 Gtr Manchester Primary Care SGA Items Prescribed Gtr Manchester Primary Care Antipsychotic Items Prescribed Q2 2011/ Greater Manchester PCT weighted prescribing of FGAs since Q4 2006/ Greater Manchester PCT weighted prescribing of SGA items since National Prescribing proportions of antipsychotic items dispensed in Q2 2011/ England Primary Care Antipsychotic Drug Expenditure ( thousands) /12: Individual Drugs 55 4

5 31 England Primary Care Antipsychotic Drug Expenditure ( thousands) /12: Individual SGA & Total FGA Drugs 32 England Primary Care Antipsychotic Drug Prescribing (Items Dispensed) /12: Individual Drugs 33 England Primary Care Antipsychotic Drug Prescribing (Items Dispensed) /12: Individual SGA & Total FGA Drugs 34 England Primary Care Antipsychotic Drug Prescribing (Items Dispensed) /12: Total SGA & Total FGA Drugs A1 Ashton, Leigh & Wigan PCT: items prescribed Q2 2011/12 A2 Ashton, Leigh & Wigan PCT: expenditure Q2 2011/12 A3 Bolton PCT: items prescribed Q2 2011/12 84 A4 Bolton PCT: expenditure Q2 2011/12 84 A5 Bury PCT: items prescribed Q2 2011/12 85 A6 Bury PCT: expenditure Q2 2011/12 85 A7 Heywood, Middleton & Rochdale PCT: items prescribed Q2 2011/12 86 A8 Heywood, Middleton & Rochdale PCT: expenditure Q2 2011/12 86 A9 Manchester PCT: items prescribed Q2 2011/12 87 A10 Manchester PCT: expenditure Q2 2011/12 87 A11 Oldham PCT: items prescribed Q2 2011/12 88 A12 Oldham PCT: expenditure Q2 2011/12 88 A13 Tameside & Glossop PCT: items prescribed Q2 2011/12 89 A14 Tameside & Glossop PCT: expenditure Q2 2011/12 89 A15 Salford PCT: items prescribed Q2 2011/12 90 A16 Salford PCT: expenditure Q2 2011/12 90 A17 Trafford PCT: items prescribed Q2 2011/12 91 A18 Trafford PCT: expenditure Q2 2011/12 91 A19 Stockport PCT: items prescribed Q2 2011/12 92 A20 Stockport PCT: expenditure Q2 2011/

6 Executive Summary Greater Manchester clozapine prescribing census. Clozapine is more effective than any other antipsychotic drug, but because of potentially serious adverse effects, is limited to prescribing in treatment resiatant schizophrenia, where 2 other antipsychotic drugs have failed. Clozapine prescribing in Greater Manchester has steadily increased over the last ten years principally as a result of research in treatment resistant schizophrenia, but also related to improved training as well as local and national prescribing guidelines. The SiGMA study developed prescription guidelines in order to monitor evidence based prescribing and this work contributed to the National Institute for Clinical Excellence (NICE) 2009 recommendations on clozapine in treatment resistant schizophrenia. As a result of recent local and national prescribing guidelines, clozapine prescriptions since 2009 have greatly increased in each Greater Manchester Trust. There was an average 7% increase in clozapine prescribing year on year from and an 18% increase from 2010 to 2011.This represented an 74% increase compared to 2003 and a 421% increase since 1996, when the Sigma audit was commenced. In addition between-site variation in clozapine prescribing ( postcode prescribing ) has decreased substantially over the time period covered by the census ( ) to a 2-fold (raw data, population-adjusted data), and a 1.5-fold, variation (population- and need-adjusted data) compared to a 26 fold (raw data), 31 fold (population adjusted) and 26 fold (need and population adjusted) recorded in The variation in clozapine prescribing between Greater Manchester Trusts is now 1.4-fold (raw data), 1.6-fold (population-adjusted data) and 1.7-fold (population- & need-adjusted data). Greater Manchester primary care antipsychotic prescribing: Most (80%) of antipsychotic drug prescribing costs are in primary care. Greater Manchester antipsychotic drug expenditure in primary care for the first quarter of 2010/11 was 4.7 million, with over 4.4 million of this spent on second generation antipsychotic (SGA) drugs. The prescribing ratio of SGA to first generation antipsychotic (FGA) drugs by item remains at a rate of 1.2:1, as the cost ratio between SGA and FGA drugs is 11.4 to 1. SGAs comprise 56% of all antipsychotic drugs prescribed across Greater Manchester, but represent 92% of antipsychotic drug cost. Antipsychotics delivered via injection (longacting injectables: FGA depots and long-acting risperidone injection) represent a low proportion of all antipsychotics in prescribed in primary care across Greater Manchester (less than 2% FGA depots, less than 1% injectable risperidone) but this is because almost all LAI drug treatment is delivered in secondary care services. We know that 6

7 approximately 35% of all patients in England with a diagnosis of schizophrenia in contact with mental health services are prescribed an LAI (depot) drug (Barnes et al., 2009). The proportion of individual SGA drugs prescribed varies between Greater Manchester PCTs and although antiquated treatments such as fluspirilene and remoxipride have largely ceased over the course of the SiGMA audit, there is more work needed to limit postcode prescribing and increase evidence based treatment across Greater Manchester. The net ingredient cost per patient for antipsychotic drugs is higher in Greater Manchester than the national and regional average; there is a large variation between PCTs, although this appears to be a consistent pattern and may be related to local differences in population and healthcare provision. England primary care antipsychotic prescribing: National antipsychotic expenditure in 2010/11 was nearly 282 million. Although antipsychotic prescribing (number of items dispensed) has doubled in the SiGMA study audit period from 1993 to 2010/11, the increased proportion of prescribing made up of SGA drugs means that antipsychotic expenditure shows a 16-fold increase over the same time period. One SGA drug, olanzapine, comprises 40% of national spend on antipsychotic drugs and 24% of antipsychotic prescribing in primary care. The total number of SGA prescriptions overtook the total FGA prescriptions during 2003 and the trend has continued. The individual FGAs to retain a notable share of antipsychotic prescribing nationally are chlorpromazine, haloperidol, trifluoperazine, sulpiride and promazine, and the LAIs in secondary care. Comparison of local antipsychotic prescribing with that seen nationally: Risperidone prescribing comprises a smaller proportion of total antipsychotic prescribing across Gtr Manchester compared with England (10% vs. 14%); quetiapine prescribing takes up a somewhat larger proportion (18% vs. 16%). Greater Manchester as a region spends more on quetiapine (30% vs. 26%), aripiprazole (11% vs. 8%) and FGA drugs (8% vs. 6%) as a proportion of total antipsychotic spend compared with the pattern seen nationally. The region spends less as a proportion of total antipsychotic expenditure on risperidone (9% vs. 14%) and slightly less on olanzapine (37% vs. 41%). Combination and high dose antipsychotic prescribing: Antipsychotic co-prescribing increases the incidence of adverse drug effects and multiplies treatment costs, with no formal evidence for increased efficacy (Hamann et al, 2003; Hayhurst et al, 2010; Taylor et al, 2000b; Yuzda, 2000). Receiving combined high doses of antipsychotic drugs is often a result of the practice of combination prescribing 7

8 (Bingefors et al, 2003; Lelliott et al, 2002) with an estimated 20% of UK patients receiving antipsychotic drugs in doses exceeding BNF (2010) guidance (Harrington et al, 2002). Recent Prescribing Observatory for Mental Health (POMH) data shows high rates in Greater Manchester of combination antipsychotic prescribing (22% of prescriptions) and high dose prescribing (19%) in inpatients. These figures are more marked when PRN prescribing is included (76% combination prescribing and 66% high dose). These figures were almost twice those seen nationally. Published surveys often exclude PRN prescribing which masks co-prescribing and high dose prescribing in acute settings. These figures highlight the extent of the impact of PRN or as required antipsychotic medication on rates of high dose and combination prescribing. Greater Manchester Mental Health Trusts appear to have higher than average rates of PRN prescribing than those observed nationally. The impact of antipsychotic prescribing on resource use: the effect of treatment with long-acting injectable risperidone (Risperdal Consta) on hospitalisation rates: Reduced hospitalisation rates constitute a substantial economic benefit to the NHS as inpatient stays make up 57% of treatment costs (Knapp et al, 2002). This is dependent on the selection of appropriate antipsychotic treatment in order to reduce hospitalisation and relapse, also any reduction in levels of relapse sufficient to warrant re-hospitalisation represents improved mental health and functioning for the patient (Matheson et al, 1994). LAI drugs are prescribed for maintenance treatment for relapse prevention. Until 2006, only FGA drugs were available in LAI form. Long-acting, injectable risperidone (Consta) has placed increased cost pressures on Mental Health Trusts in Greater Manchester, yet the majority of evidence concerning Consta adherence and rate of relapse was derived from non-uk modelling studies (NICE, 2009) and there is no formal evidence that it is safer or more effective than FGA LAIs, despite being times more expensive. We aim to audit its use in detail. The first stage of the audit involved researching and testing methods of identifying patients eligible for inclusion in the audit. A power calculation indicated that 70 patients are required in each of the 3 Greater Manchester Mental Health Trusts to facilitate the study. Data on hospitalisation is to be collected retrospectively from Trust information departments. Control groups will also be matched on the basis of age, gender and previous rates of hospitalisation. Development of a patient-rated side effect rating scale: Nonadherence to prescribed treatment can result from the experience of side effects leading to an increased risk of relapse and re-hospitalisation: the main risk for psychotic relapse within five years of first treatment is nonadherence in 82% of patients (Robinson 8

9 et al, 1999). It is the experience of side effects which increasingly drives patient and clinician choice between available antipsychotic drugs as all antipsychotics, with the exception of clozapine, have similar efficacy. The 10 item patient-rated side effect scale has been developed from data gathered for the CUtLASS study (Cost Utility of the Latest Antipsychotics in Severe Schizophrenia: Jones et al, 2006; Lewis et al, 2006a; 2006b) which comprised two randomised controlled trials (RCTs) recruiting from five centres across the UK. Treatment-related side effects were measured with the Simpson-Angus scale (Simpson & Angus, 1970), the Barnes Akathisia scale (Barnes, 1989), the Assessment of Involuntary Movements Scale, AIMS (Guy, revised 1976) and the Antipsychotic Non-Neurological Side-Effects Rating Scale, ANNSERS (Ohlsen et al., 2008; Yusufi et al, 2005). Factor analysis of the 61 individual items on the four side effect scales was undertaken and this lead to the creation of a ten-item rating scale (see Appendix). The scale will be piloted in different care settings to establish its acceptability to patients and carry out validation of the scale prior to auditing its use. The validation of this scale is currently underway under the supervision of Dr Richard drake in North Manchester. 9

10 Recommendations 1. Clearer recording in patient casenotes, especially of current antipsychotic drug treatment (drug and dose) and ethnicity, to facilitate audit. 2. 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. 3. Further tracking of antipsychotic drug prescribing is recommended to identify whether findings from pragmatic trials such as CUtLASS (Jones et al, 2006; Lewis et al, 2006a; 2006b) in the UK and CATIE (Lieberman et al, 2005) in the US, which indicate the non-superiority of more expensive SGA drugs over FGAs, will lead to any increase in the use of FGA drugs and any corresponding decrease in the use of SGA agents. 4. Relatively high rates of antipsychotic drug prescribing in Greater Manchester are in part explained by local population demographics known to affect incidence rates and outcomes of schizophrenia, as shown in previous SiGMA studies. However, continued audit is needed to ensure these rates are not inappropriate. 5. Clear guidance as to the limitations and risks associated with combination, including PRN, antipsychotic prescribing need implementation. 6. Clozapine prescribing is now more evidence-based and consistent across Greater Manchesteralthough still less than rates recommended by NICE (2009). Continued audit is needed to improve this further.a prescribing policy change in the Bury PCT district in 2010 has led to measurable prescribing shifts and cost savings. The impact of these changes on patient outcomes is being assessed in an NIHR-funded project and the results of this will be disseminated in early

11 Available Guidance Treatment-Resistant Schizophrenia NICE guidance defines treatment-resistant schizophrenia (TRS) as, a lack of satisfactory clinical improvement despite the sequential use of the recommended doses for six to eight weeks of at least two antipsychotics, at least one of which should be an atypical. Clozapine prescribing NICE (2009) recommends, clozapine to people with schizophrenia whose illness has not responded adequately to treatment despite the sequential use of adequate doses of at least two different antipsychotic drugs. At least one of the drugs should be a non-clozapine secondgeneration antipsychotic. Monitoring of treatment-related side effects NICE (2009) recommend that the side effects of treatment should be monitored and recorded regularly and systematically throughout treatment and especially during titration. Prescribing of depot antipsychotic treatment NICE (2009) suggests that the prescriber should Consider offering depot/ long-acting injectable antipsychotic medication to people with schizophrenia (1) who would prefer such treatment after an acute episode (2) where avoiding covert non-adherence (either intentional or unintentional) to antipsychotic medication is a clinical priority within the treatment plan. Choice of first-line antipsychotic drug treatment NICE (2009) recommends that, 11 The choice of drug should be made by the service user and healthcare professional together, considering the relative potential of individual antipsychotic drugs to cause extrapyramidal side effects (including akathisia), metabolic side effects (including weight gain) and other side effects (including unpleasant subjective experiences).

12 Antipsychotic co-prescribing NICE (2009) cautions, do not initiate regular combined antipsychotic medication, except for short periods (for example, when changing medication). 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. The British National Formulary (BNF, 2010) 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 (Taylor et al, 2009) suggest that, antipsychotic monotherapy is desirable and should be the norm. Clozapine augmentation NICE (2009) recommends, adding a second antipsychotic to augment treatment with clozapine. An adequate trial of such an augmentation may need to be up to 8 10 weeks. Choose a drug that does not compound the common side effects of clozapine. High dose antipsychotic prescribing NICE guidance (2009) recommends that the clinician, justify and record reasons for dosages outside the range given in the BNF [British National Formulary] or SPC [Summary of Product Characteristics]. The Royal College of Psychiatrists revised consensus statement (RCPsych, 2006) concludes that, current evidence does not justify the routine use of high-dose antipsychotic medication in general adult mental health services, either with a single agent or combined antipsychotics. 12

13 SiGMA: Schizophrenia in Greater Manchester: Audit Introduction Schizophrenia remains a major public health problem, with direct costs to the NHS of over 2 billion per year. Although psychological therapies are increasingly important, the mainstay of treatment for schizophrenia remains antipsychotic drugs used to treat acute symptoms and maintain remission. Schizophrenia has been treated with conventional, or first generation antipsychotic (FGA) drugs since the 1950s and with atypical, or second generation antipsychotic (SGA) drugs since the 1990s. Despite claims that SGAs offer better efficacy and tolerability, two large scale pragmatic trials including one arising from the early SiGMA data (Jones et al, 2006) have shown little difference despite increased acquisition cost for SGAs, with the sole exception of clozapine which has shown significant benefit in treatment resistant schizophrenia (Lewis et al, 2007). The SiGMA study audits adherence to evidence-based treatment guidelines, such as NICE, in the antipsychotic drug treatment of schizophrenia. Ongoing audits are informed by NICE guidance (updated March 2009) on the antipsychotic drug treatment of schizophrenia and future audits will monitor adherence to those guidelines. Outline of work: Audit of clozapine prescribing across Greater Manchester. Clozapine rates are adjusted to take into account current population and need levels. Prescribing rates are compared with previous data to identify any emerging trends in prescribing and also compared across the three Greater Manchester Trusts. Audit of primary care antipsychotic prescribing and expenditure across Greater Manchester. Prescribing is compared with previous figures to identify trends in antipsychotic prescribing and comparisons are made between Greater Manchester PCTs. Summary of primary care antipsychotic prescribing and expenditure across England. Comparison of local antipsychotic prescribing and expenditure with that seen nationally. Combination and high dose antipsychotic prescribing. Audit the impact of antipsychotic drug treatment on rates of hospitalisation: design and development of an audit to examine whether use of Risperidone Consta has led to any reductions in hospitalisation rates. 13

14 Development of a draft patient-rated brief side effect rating scale for use across care settings to facilitate audit of side effect monitoring. 14

15 Greater Manchester Clozapine Prescribing Census Background Reasons for choice First time or re-audit: ongoing/ re-audit National/ Regional priority: Greater Manchester Secondary Care prescribing data Aim of audit: to track clozapine prescribing across Greater Manchester and to compare patterns and trends of clozapine prescribing between the Mental Health provider sites and Mental Health Trusts of Greater Manchester. Introduction Clozapine is conclusively superior to conventional, or first generation antipsychotic (FGA) drugs in treatment-resistant schizophrenia (TRS), in terms of symptoms, side effects and adherence to treatment (Chakos et al, 2001) and to other atypical, or second generation antipsychotics (SGAs) in effectiveness (Lewis et al, 2006a; 2006b). Cochrane review supports its cost-effectiveness (Essali et al, 2009) as does local SiGMA data (Hayhurst, Brown & Lewis, 2002). Patients and their families also report positive benefit from clozapine treatment (Dickson et al, 1995; Najarian, 1995; Taylor et al, 2000a; Waserman & Criollo, 2000; Wolfson & Paton, 1996). Clozapine was licensed in 1990 for 3 rd line use. NICE has recommended its routine use in treatment-resistant schizophrenia since their first guidance on the treatment of schizophrenia; issued in This recommendation was repeated in the March 2009 NICE update (NICE, 2009) which supported a specific recommendation for clozapine for people whose illness does not respond adequately to other antipsychotic medication. 15

16 Treatment-resistant schizophrenia (TRS) has previously been defined by NICE as a lack of satisfactory clinical improvement despite the sequential use of the recommended doses for six to eight weeks of at least two antipsychotics, at least one of which should be an atypical. Approximately 30% of patients with schizophrenia will have TRS as defined by NICE but numbers of patients prescribed clozapine remain far lower than rates of TRS; Greater Manchester data indicates that less than a third of patients eligible for clozapine treatment are currently prescribed the drug across the region. This corresponds with national data, which reports that 30% of eligible patients receive clozapine across England (Downs & Zinkler, 2007). 16

17 Methodology Patients: Individual patients were not involved in the audit. Methods: Clozapine prescribing data is obtained via hospital based mental health pharmacists. Such data has been available since 1996 and now covers 15 years of prescribing data. This enables data to be compared with that of previous years to track the provision of clozapine on a longitudinal basis, plus allows comparisons to be made between the Mental Health provider sites across the region and between the three Mental Health Trusts covering Greater Manchester. Greater Manchester Mental Health Trusts have been re-configured during the timeperiod covered by this study. Clozapine prescribing data for each site is adjusted to take into account population size, using the most current figures for that site s catchment population. The population-adjusted figure is the rate of clozapine prescribing per 100,000 population. Using this data, the area of Greater Manchester with the highest population is Stockport and the area with the lowest population is North Manchester. Population-adjusted prescribing is also adjusted to take into account the calculated psychiatric need of the area. This adjustment uses the MINI (Mental Illness Needs Index) to adjust for local levels of psychiatric need (Glover, 1998). The MINI is a calculation based on the predicted psychiatric admission rate for the area in question divided by the predicted psychiatric admission rate for England as a whole. Using this index, the area of Greater Manchester with the highest level of psychiatric need is North Manchester, whilst the area with the lowest level of need is Tameside. All areas of Greater Manchester have an index of above one, indicating levels of psychiatric need higher than the national average in all parts of the region, typical of the needs in urban and semi-urban areas nationally (Glover, 1998). Clozapine prescribing data by Mental Health provider site is anonymised, as in previous reports: the key for site identification is available from the author of the report on request. Prescribing data is, however, identified by Mental Health Trust. 17

18 Results Clozapine prescribing Figure 1: Greater Manchester Clozapine Prescribing Number of clozapine prescriptions ( ) # of Prescriptions Figure 1 shows that the number of patients prescribed clozapine across Greater Manchester, as a whole, has increased from 281 patients in the 1996 census to 1464 patients in the 2011 census (a 421% increase over the 15-year period covered by census data). The graph shows the increase in clozapine prescribing following a somewhat regular gradient (year on year) since 1998, potentially associated with the publication of clozapine s efficacy in TRS ( ) and with an additional increase observed between 2008/2009 around the time of the revised NICE recommendations on its usage. 18

19 Figure 2: Clozapine Prescribing by District: Raw Data Raw Data # of Prescriptions Tameside Rochdale North Manchester Central Manchester South Manchester Trafford Bolton Bury Oldham Salford Stockport Figures 2 to 4 show clozapine prescribing by the 11 sites across Greater Manchester submitting prescribing data for inclusion in the census. This data is presented in Appendices Tables A1, A2 and A3. Sites which have been consistently high prescribers of clozapine during the time period covered by the census are Stockport, Central and South Manchester. Tameside was the third highest prescriber of clozapine when the census began in 1996 but prescribing for this site has not increased at the same rate as other sites resulting in their position of 10 th (raw data), equal 10 th (population adjusted data) and 8 th out of 11 sites (population & need adjusted data) in clozapine prescribing by Sites maintaining consistently mid-range prescribing (neither high nor low in comparison with the other sites) include Bolton and Trafford. Salford had a low baseline level of prescribing in 1996 but has increased prescribing at a greater rate than other sites since that date and now is the highest prescriber in GM (raw data). Rochdale had maintained relatively low rates of prescribing in comparison with the other sites. This site was the fourth lowest prescriber in 1996 and the second lowest prescriber in 2009, but increased prescribing rates in the last two years to be equal fifth 19

20 highest when adjusted for need and population in Bury has been the lowest prescriber of clozapine since 1996 although their increase, year on year, shows a much steeper growth from 2007 onwards. Bury has the largest increase in prescribing over time, compared with their baseline in 1996, representing a 4500% increase in raw data terms. Other sites to demonstrate large increases in prescribing over the time period covered by the clozapine census are North Manchester and Salford..Figure 3: Clozapine Prescribing by District: Population-Adjusted Data Population Adjusted Data # of Prescriptions Tameside Rochdale North Manchester Central Manchester South Manchester Trafford Bolton Bury Oldham Salford Stockport Adjusting the data to take into account population size leads to a degree of grouping of the 11 sites. North, Central and South Manchester have the highest, and very similar rates of population-adjusted prescribing. Salford now has a more modest level of adjusted prescribing but remains the 3 rd highest prescriber. The remaining sites (apart from Bury) all have quite similar rates of adjusted prescribing, increasing relatively steadily year on year. Bolton and Tameside have the lowest rate of prescribing when figures are adjusted to take into account population size, followed by Bury and Trafford. 20

21 Figure 4: Clozapine Prescribing by District: Population- & Need-Adjusted Data Population & Need Adjusted Data # of Prescriptions Tameside Rochdale North Manchester Central Manchester South Manchester Trafford Bolton Bury Oldham Salford Stockport Accounting for local psychiatric need, in addition to population size, provides a more relative comparison between sites and leads to Oldham being the highest prescriber in Greater Manchester. South Manchester now takes second place in rates of adjusted prescribing, followed closely by Central Manchester. Bury has the lowest rate of clozapine prescribing even when data is adjusted to take into account population need as well as size but this is a significant improvement in the last few years with an increase in prescribing of 513% (raw data), 525% (population adjusted) and 500% (need and population adjusted) since The need and population adjusted data shows most sites with comparable rates of prescriptions in 2011, there are significant variations in previous years but all sites (with the exception of Salford which made one less clozapine prescription in 2011 to 2010) are increasing or maintaining their prescribing rates. There is a clear necessity to continue monitoring this data as this more recent upsurge in areas like Bury may taper off or regress, the initial increase, while very encouraging, suggests that clozapine prescribing has been adopted in all sites up to 2011 but further audits will be required to see whether this practice is maintained in coming years. The Greater Manchester results are 21

22 encouraging that NICE guidelines and evidence based prescribing are making an impact in each district, especially in the last few years. Variation between districts Figure 5: Clozapine prescribing: Variation between districts Variation in Clozapine Prescribing between GM Districts Population & Need-Adjusted Data Population-Adjusted Data Variation Raw Data Figure 5 shows variation in the use of clozapine across the 11 Greater Manchester sites. In terms of raw data the degree of clozapine postcode prescribing has fallen from a high of a 30-fold variation in 1997 to the current 2-fold variation in The variation does not show a direct reduction; the graph shows the variation rising between 1999 and 2000 before beginning to fall again to the low variation seen in Clozapine prescribing data adjusted to take into account population size also shows a reduction from the high of a 31-fold variation between Greater Manchester sites in 1996 to the 2011 two-fold variation between sites. The population-adjusted variation also 22

23 shows a second more exaggerated peak than that seen with the raw data, where prescribing variation increased between 1999 and 2002 and then noticeably decreases. Adjustments in clozapine prescribing to take into account both population size and local psychiatric need shows the same pattern of variation between districts with a reduction from a high of a 26-fold variation in 1996 to the fold variation. Variation between Trusts Greater Manchester is covered by three NHS Trusts; Manchester Mental Health & Social Care Trust (MMHSCT), Pennine Care NHS Foundation Trust; and Greater Manchester West Mental Health Foundation Trust (formally Bolton, Salford & Trafford Mental Health NHS Trust). Prescribing data grouped into the areas covered by these three Trusts is available from 2003 onwards and is summarised in Table A4. Figure 6: Clozapine prescribing by Greater Manchester Trusts: Raw Data Clozapine Prescribing by Trust (raw data) # of Prescriptions MMHSCT Pennine Care MHF Gtr Man West Figure 6 indicates that the highest prescribing Trust is Pennine Care, followed by MMHSCT, followed by Greater Manchester West. The graph shows that clozapine prescribing has followed this order of use since 2003, with prescribing by Greater Manchester West mirroring the rate of increase seen in MMHSCT, whereas the rate of growth in Pennine Care clozapine prescribing has increased away from the other two Greater Manchester Trusts since

24 The Trust with the largest growth in clozapine prescribing over the seven years covered by this data (2003 to 2011) is Pennine Care with a 97% increase. Greater Manchester West had a 64% increase and MMHSCT a 57% increase over the same timeperiod. Figure 7: Clozapine prescribing by Trust: Population-Adjusted Data Population Adjusted Clozapine Prescribing by Trust # of Prescriptions MMHSCT Pennine Care MHF Gtr Man West Raw clozapine prescribing data seen in Figure 6 adjusted to take into account population size shows a slightly different picture. The lower population size seen in the Trust covering the central area of Greater Manchester (MMHSCT) adjusts the raw data to now place MMHSCT as the highest (population-adjusted) prescriber of clozapine. 24

25 Figure 8: Clozapine prescribing by Trust: Population- & Need- Adjusted Data Need and Population Adjusted Clozapine Prescribing by Trust # of Prescriptions MMHSCT Pennine Care Gtr Man West Adjusting the data to also take into account the psychiatric need of those areas covered by each Trust reflects the pattern seen with the raw prescribing data in Figure 6 whilst increasing the variation between the three Trusts. Table A4 also shows the variation in clozapine prescribing between the three Greater Manchester Trusts. This highlights that, although Figure 5 demonstrates a noticeable degree of variation between the 11 sites of Greater Manchester over the census time period, this data when collapsed across the three Trusts shows much less prescribing variation. Variation between the three Trusts (raw data) has remained relatively constant since a 1.2-fold variation in 2003, falling to a 1.1-fold variation in 2006 and 2007, and subsequently rising slightly to a 1.3-fold variation in 2009 and 1.4-fold variation in The variation in population-adjusted clozapine prescribing also remains quite constant at a 1.7-fold variation throughout the time-period covered by the census, reaching a 1.6-fold variation by The change in variation in clozapine prescribing between the three Trusts when adjusted for need and population has risen slightly from a 1.5-fold variation in 2003, to a 1.6-fold variation in 2008, continuing to a 1.7-fold variation in

26 Figure 9: Clozapine prescribing: Variation between Trusts Variation in Clozapine Prescribing between Trusts 1.8 Variation Population- & Need- Adjusted Data Population-Adjusted Data Raw Data Comparison with published findings A paper containing clozapine prescribing data for Greater Manchester, collected for the SiGMA study was published in 2000 (Purcell H & Lewis S. Postcode prescribing in psychiatry: Clozapine in an English county. Psychiatric Bulletin 2000, 24, ). This paper reported a 34-fold variation in population- and deprivation-adjusted clozapine prescribing between the (then) 12 Mental Health provider sites across Greater Manchester. The authors concluded that clozapine postcode prescribing reflects variations in evidence-based clinical practice (Purcell & Lewis, 2000). These findings compare with a 1.5-fold variation in population- and need-adjusted clozapine prescribing between the (now) 11 sites during Prescribing data collected by the SiGMA study was also published in 2003 in a paper examining postcode prescribing or geographical variations in antipsychotic prescribing (Hayhurst K, Brown P, Lewis S. Postcode prescribing for schizophrenia [Editorial]. British Journal of Psychiatry 2003, 182, ). This paper reported a 16-fold variation in 26

27 population-adjusted clozapine prescribing between the (then) 12 Mental Health provider sites across Greater Manchester. The authors concluded that factors maintaining the observed variation in clozapine prescribing include individual practitioner preferences and prescribing skills (Hayhurst et al, 2003). These findings compare with a 2-fold variation in population-adjusted clozapine prescribing between the 11 Greater Manchester sites during A paper reporting national clozapine prescribing rates was published in 2007 based on data collected during 2006 (Downs J & Zinkler M. Clozapine: national review of postcode prescribing. Psychiatric Bulletin 2007, 31, ). This study collected data from 60% of English Mental Health Trusts finding a 5-fold variation in prescribing rates adjusted to take into account population size and psychiatric need (using the MINI). These findings compare with a 1.3-fold variation between the three Greater Manchester Mental Health Trusts during the same timeperiod (2006) which had risen to a 1.7-fold variation in adjusted prescribing rates between Greater Manchester Trusts during Recent research on clozapine prescribing and NICE guideline adherence (Mortimer et al., 2010) has shown that nearly 50% of patients who need clozapine on clinical grounds are not receiving it, and while there are a range of factors impacting on each clinical decision it suggests that there remains a deficit in the number of treatment resistant schizophrenia patients being prescribed clozapine. 27

28 Summary The number of patients prescribed clozapine across Greater Manchester was 1464 in the 2011 census (a 421% increase since first collection of census data in 1996). Variation in clozapine prescribing has fallen from a high of a 30-fold variation in 1997 to a 2-fold variation in 2011 (raw data), from a 31-fold variation in 1996 to a 2-fold variation in 2011 (population-adjusted data), and from a 26-fold variation in 1996 to a 1.5-fold variation in 2011 (population- and need-adjusted data). The Greater Manchester Trust currently prescribing clozapine at the highest rate is Pennine Care (raw data) although when prescribing is adjusted to take into account population size, MMHSCT is the highest prescribing Trust. Of the three Greater Manchester Trusts, Pennine Care has had the largest increase (97%) in rates of clozapine prescribing over the timeperiod of data collection for the reconfigured Trusts (2003 to 2011). Clozapine prescribing between Trusts shows a 1.4-fold variation (raw data), a 1.6-fold variation (population-adjusted data) and a 1.7-fold variation (population- & needadjusted data) in the 2009 census. Action Re-audit planned: this is an ongoing audit with figures being updated annually. 28

29 Primary care antipsychotic prescribing and expenditure across Greater Manchester Background Reasons for choice First time or re-audit: ongoing/ re-audit National/ Regional priority: Greater Manchester Primary Care prescribing data Aim of audit: to track antipsychotic prescribing, and associated spending, across Greater Manchester and compare patterns and trends of antipsychotic prescribing, including that of individual second generation (SGA), or atypical, antipsychotic drugs, between Primary Care Trusts (PCTs) across Greater Manchester. Introduction Previous SiGMA audits have highlighted the rapid increase in prescribing, and hence, expenditure, on second generation antipsychotic (SGA) drugs, as well as providing evidence that rates of antipsychotic prescribing can partly be explained by population deprivation and need (Hayhurst, Brown & Lewis, 2003). Most (~80%) of the costs of antipsychotic drug prescribing are met in primary care where Greater Manchester expenditure for the year 2007/08 was 16.2 million, with 15.1 million of this comprising SGA spend. This compares with the same period for 1997/98 with an SGA spend of 1.3 million. Data on primary care antipsychotic prescribing and expenditure across Greater Manchester is obtained via Primary Care Trusts and the Regional Drug and Therapeutics Centre at the Wolfson Unit. This prescribing data is compared with previous figures to identify trends in antipsychotic prescribing and make comparisons between Greater Manchester PCTs. Previous SiGMA findings fed into the design and rationale for the UK HTA-funded CUtLASS (Cost Utility of the Latest Antipsychotics in Severe Schizophrenia), the results of which indicated that the advantages of more expensive SGA drugs over first generation antipsychotic (FGA) drugs were not significant and that FGAs were more cost effective in the treatment of schizophrenia (Jones et al, 2006; Lewis et al, 2006a; 2006b). These 29

30 findings received international attention (for example, front page Washington Post: Oct ) and have been widely cited in available research literature. Similar findings have emerged from the US, where the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study (Lieberman et al, 2005) compared four SGAs (olanzapine, quetiapine, risperidone and ziprasidone) with a representative FGA; perphenazine. Perphenazine was comparably effective to three of the four SGA drugs used and did not have greater side effects. Olanzapine was slightly more effective but linked to greater weight gain (Chakos et al, 2006; Haddad & Dursun, 2006). Prescribing audits such as this can provide information on patterns and trends of SGA and FGA prescribing to illustrate whether the impact of these published and widelydisseminated findings, in addition to revised NICE guidance (NICE, 2009), which has taken these results into account, has led to any increase in the use of FGA drugs and any corresponding decrease in the use of SGA drugs across the region. 30

31 Methodology Patients: Individual patients were not involved in the audit. Methods & Background: The SiGMA study initially audited spending on second generation, or atypical (SGA), antipsychotics across Greater Manchester due to the high costs associated with this class of drug. Prescribing data were obtained from the (then) six health authorities of Greater Manchester who provided expenditure details for the use of SGAs in primary care across the region. This dataset extended from April 1996 through to March 2002; covering spending on clozapine, risperidone, olanzapine, quetiapine, amisulpride, zotepine, and when used, sertindole. This data was used to illustrate the large rise in the prescription of these newer antipsychotic drugs during this period of time (see Figure 12); reported in an Editorial in the British Journal of Psychiatry, together with an examination of the extent of postcode prescribing in the use of these newer drugs (Hayhurst, Brown & Lewis 2003: 182; ). 700, , , , , , ,000 0 Figure 10: Gtr Manchester Primary Care Total SGA Spend Apr-96 Oct-96 Apr-97 Oct-97 Apr-98 Oct-98 Apr-99 Oct-99 Apr-00 Oct-00 Apr-01 Oct-01 Apr-02 During this 6-year period, monthly SGA spend for the region rose from 31K in April 1996 through to 610K in March 2002, i.e. a 20-fold spending increase. 31

32 This initial dataset also highlighted the dramatic growth in the proportion of total SGA spend taken up by one SGA drug, olanzapine (see Figure 13). 400,000 Figure 11: Gtr Manchester Primary Care Individual SGA Spend , , , , , ,000 Clozapine Risperidone Olanzapine Quetiapine Amisulpride Zotepine Sertindole 50,000 0 Apr-96 Jul-96 Oct-96 Jan-97 Apr-97 Jul-97 Oct-97 Jan-98 Apr-98 Jul-98 Oct-98 Jan-99 Apr-99 Jul-99 Oct-99 Jan-00 Apr-00 Jul-00 Oct-00 Jan-01 Apr-01 Jul-01 Oct-01 Jan-02 Olanzapine was being prescribed across the region by October 1996; by January 1998 (15 months later) spending had overtaken that on risperidone (the previous market leader across the region). By March 2002, monthly expenditure on olanzapine was 340K and the drug commanded 56% of total SGA spend across the region s primary care providers. Primary care health services across Greater Manchester have since been reconfigured: the region is now served by ten Primary Care Trusts (PCTs). These are Ashton, Leigh & Wigan PCT; Bolton PCT; Bury PCT; Heywood, Middleton & Rochdale PCT; Manchester PCT; Oldham PCT; Tameside & Glossop PCT; Salford PCT; Stockport PCT; and Trafford PCT. Antipsychotic prescribing data has been made available to the SiGMA study for these PCTs from the third quarter of 2004/05 and from the Wolfson Unit at the Regional Drug and Therapeutics Centre from 1 st quarter 2005/2006; National expenditure and prescription rates are available from 4 th quarter 2007/2008 for comparison. This report summarises these prescribing figures from these date until the most recent available. 32

33 Results Antipsychotic Prescribing Expenditure Figure 12 shows total SGA spend against total FGA spend. Total FGA expenditure remains below 400K per quarter during the whole timeperiod. Total SGA spend rises from just over 3,000K per quarter to 4,052K for the last quarter of 2008 before dropping to just under 4,000K for the last quarter of 2008/09 and first quarter of 2009/10. The cost increases further to 4,523K for the 2 nd quarter of 2011/2012. Figure 12: Gtr Manchester Primary Care SGA & FGA Spend ,000,000 4,500,000 4,000,000 3,500,000 3,000,000 Cost 2,500,000 2,000,000 Total SGAs Total FGAs 1,500,000 1,000, ,000 0 Q1 05/06 Q3 05/06 Q1 06/07 Q3 06/07 Q1 07/08 Q3 07/08 Q1 08/09 Q3 08/09 Q1 09/10 Q3 09/10 Q1 10/11 Q3 10/11 Q1 11/12 33

34 Figure 13 illustrates the ratio of SGA to FGA spend. During the timeperiod examined, the ratio only slightly falls below 10:1, reaching a peak of 14.5 to 1 during the last quarter of 2009/10. Figure 13: Gtr Manchester Primary Care Ratio of SGA to FGA Spend Ratio of SGA cost to FGA cost Q1 05/06 Q3 05/06 Q1 06/07 Q3 06/07 Q1 07/08 Q3 07/08 Q1 08/09 Q3 08/09 Q1 09/10 Q3 09/10 Q1 10/11 Q3 10/11 Q1 11/12 Cost Ratio FGA spend divided into depot FGA drugs and oral FGA drugs and the ratio of depot drugs to oral drugs is set out in Figures 14 and 15 respectively. Although given here, these data are of limited relevance overall, since the majority of LAI (depot) costs fall to secondary care. 34

35 350 Figure 14: Gtr Manchester Primary Care Spend: Depot FGA and Oral FGA Cost (Thousands) Q1 07/08 Q2 07/08 Q3 07/08 Q4 07/08 Q1 08/09 Q2 08/09 Q3 08/09 Q4 08/09 Q1 09/10 Q2 09/10 Q3 09/10 Q4 09/10 Q1 10/11 Q2 10/11 Q3 10/11 Q4 10/11 Q1 11/12 Q2 11/12 Depot FGAs Oral FGAs Spending on depot FGAs remains at below 42K per quarter during the timeperiod, falling to a low of 32K by the first quarter of 2009/10. Oral FGA spend shows a different pattern, with expenditure increasing until the second quarter of 2008/09 when spending begins to fall. 35

36 Figure 15: Gtr Manchester Primary Care Spend: Ratio of Oral FGA to Depot FGA Ratio of FGA Depots to FGA Oral cost 10 8 Cost Ratio Q1 07/08 Q3 07/08 Q1 08/09 Q3 08/09 Q1 09/10 Q3 09/10 Q1 10/11 Q3 10/11 Q1 11/12 Figure 15 shows spending on FGAs rising from a ratio of oral to depot FGAs of just less than 6:1 to almost 10:1 over the four year period. Spending on each individual SGA drug is set out in Figure