Quality of prescribing for schizophrenia: Evidence from a national audit in England and Wales
Introduction
Antipsychotic drugs have been the mainstay for the management of schizophrenia for over half a century. Their efficacy has been established for the treatment of acute episodes (National Institute for Clinical Excellence, 2009), and for maintenance treatment by substantially reducing the risk of relapse (Leucht et al., 2012b, Leucht et al., 2012a). The benefits of these drugs must however be weighed against their adverse effects (Carlson et al., 2006, Leucht et al., 2012b). Recommendations from the British Association for Psychopharmacology (Barnes, 2011) and the NICE guideline (National Institute for Clinical Excellence, 2009) recommend avoiding antipsychotic polypharmacy in the majority of cases. Also, there is no convincing evidence that doses of antipsychotic drugs higher than the recommended maximum advised in the BNF (British National Formulary) (BMJ Group and RPS Publishing, 2013) afford additional clinical benefit over standard doses. High doses lead to greater risk of dose-related adverse effects such as cardiac sudden death (Barnes, 2011) and polypharmacy has been linked to higher rates of metabolic syndrome and lipid markers of insulin resistance (Correll et al., 2007). Nevertheless, previous studies both in the UK (Paton et al., 2008) and worldwide (Agid et al., 2013, Faries et al., 2005, Ganguly et al., 2004, Kreyenbuhl et al., 2007, Procyshyn et al., 2001, Sim et al., 2004) have shown that high dose antipsychotic prescribing and polypharmacy are common practice. An audit of antipsychotic usage in New Zealand confirmed UK findings (Lelliott et al., 2002) that antipsychotic polypharmacy is strongly associated with a combined daily dose in excess of standard practice (Humberstone et al., 2004). Similarly, a Canadian study reported that a third of patients are discharged on an antipsychotic polypharmacy regimen (Procyshyn et al., 2001). Studies in the US (Faries et al., 2005, Ganguly et al., 2004) and East Asia (Sim et al., 2004) found antipsychotic polypharmacy to be present for approximately 50% of patients.
The term “treatment resistant” in schizophrenia is used to describe people who have not adequately responded to medication despite adequate dose, duration and adherence (National Institute for Clinical Excellence, 2009). Since the average rate of non-adherence among patients with schizophrenia has been reported as 58% (range 24–90%) (Cramer and Rosenheck, 1998) adherence should always be assessed in cases of non-response (National Institute for Clinical Excellence, 2009). Furthermore, studies have shown that patients with psychosis and coexisting substance misuse generally show poorer response to treatment (National Collaborating Centre For Mental Health, 2011). Where treatment resistance for schizophrenia does exist, the superiority of clozapine against other agents has been established in large pragmatic clinical trials such as CATIE (McEvoy et al., 2006) and CUtLASS (Lewis et al., 2006) and yet, low rates of clozapine use are still apparent in clinical practice (Weissman, 2002). Guidelines from both the UK (NICE (National Institute for Clinical Excellence, 2009)) and the US (Patient Outcomes Research Team —PORT (Buchanan et al., 2010)) recommend that clozapine should be offered to all patients who continue to experience clinically significant symptoms after two adequate trials of other antipsychotics (National Institute for Clinical Excellence, 2009). Nevertheless, one study found that patients had received on average five antipsychotics before being prescribed clozapine which had been delayed for an average of five years longer than is clinically desirable (Taylor et al., 2003). Clinician׳s knowledge, attitudes and preferences are likely predictive factors for the variation in clozapine prescribing patterns (Patel, 2012). Furthermore, not all treatment resistant patients will respond adequately to clozapine and there is a lack of clear guidance on how to manage those who fail to respond. Despite limited evidence and modest improvement at best (Taylor et al., 2012), NICE suggests considering the addition of a second antipsychotic drug to clozapine to augment its effects (National Institute for Clinical Excellence, 2009). In contrast, the PORT guidelines do not support augmentation therapy due to insufficient efficacy and safety data (Buchanan et al., 2010).
The National Audit of Schizophrenia (NAS) set out to obtain a comprehensive picture of the quality of care received by individuals with schizophrenia and schizoaffective disorder in England and Wales. Since a national guideline already exists (National Institute for Clinical Excellence, 2009), the audit objective was to examine whether this was being implemented and to prompt improvements in the care of patients with these conditions. Specifically it aimed to quantify the degree of prescribing of antipsychotics at high dose, the rates for antipsychotic polypharmacy, and also the nature of clozapine prescribing at a national level, thereby overcoming concerns about sampling and generalisability of smaller scale studies.
Section snippets
Setting
NAS is a cross-sectional survey of patients involving retrospective examination of clinical records and collection of specific contemporaneous data. It is an audit of practice at the level of individual Trusts and does not allow conclusions to be drawn at the level of individual clinical teams. The term ׳Trust׳ has been used to refer to both English Trusts and Welsh Health Boards throughout. All Trusts in England and Wales were expected to participate if they provided care or treatment in the
Sample characteristics
The mean number of records returned per Trust was 85 (SD 20, range 17–134); 83% of included Trusts achieved at least 73 records; 27% of Trusts achieved 100 records. Twenty-eight Trusts reported that they used the central identification of patients sampling option, and 10 reported that they used the identification through the community mental health teams sampling option, Four used other sampling methods, which included a combination of the two sampling options. The remaining 18 Trusts did not
Principal findings
The National Audit for Schizophrenia provides the largest systematically collected UK database of antipsychotic prescribing for people with schizophrenia and schizoaffective disorder. It builds on former national (Paton et al., 2008) and international (Faries et al., 2005, Humberstone et al., 2004, Procyshyn and Zerjav, 1998) antipsychotic prescribing audits by examining several key standards directly associated with NICE guidance (National Institute for Clinical Excellence, 2009) which are
Role of funding source
The National Audit of Schizophrenia (NAS) is managed by the Royal College of Psychiatrists׳ (RCPsych) College Centre for Quality Improvement (CCQI). It is commissioned by the Healthcare Quality Improvement Partnership (HQIP) as part of the National Clinical Audit and Patient Outcomes Programme (NCAPOP), which is funded by NHS England. HQIP had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the article; and in the decision to submit the
Contributors
MXP conducted the statistical analysis, interpreted the findings and co-wrote the first draft of the manuscript. DB managed the literature search, interpreted the findings, and co-wrote the first draft of the manuscript. SJ managed the database and conducted the statistical analysis. KZ, MJC and DS oversaw the project, including aspects of study design, tool design, and recruitment of sites, and also contributed to interpretation of the findings. SJC co-wrote the first draft of the manuscript,
Conflict of interest
MXP holds a Clinician Scientist Award supported by the National Institute for Health Research and has also received consultancy fees, lecturing honoraria, and/or research funding from Janssen, Lilly, Endo, Lundbeck, Otsuka and Wyeth and has worked or is currently working on clinical trials and studies for Janssen, Amgen and Lundbeck. DB has received consultancy fees or speaker honorarium from Novartis, Astra Zeneca, Eli Lilly and Eisai. DS is a current member of the Guideline Development Group
Acknowledgements
With grateful thanks to the participating 60 Trusts and Health Boards including clinicians, support staff, medical directors, governance and audit personnel, as well as the patients and carers who completed the audit forms and members of the Advisory Group, especially TRE Barnes and C Paton for their guidance during data cleaning.
References (42)
- et al.
Antipsychotic response in first-episode schizophrenia: efficacy of high doses and switching
Eur. Neuropsychopharmacol.
(2013) - et al.
Antipsychotic prescription patterns in outpatient settings: 24-month results from the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study
Eur. Neuropsychopharmacol.
(2008) - et al.
Diabetes mellitus and antipsychotic treatment in the United Kingdom
Eur. Neuropsychopharmacol.
(2006) - et al.
Does antipsychotic polypharmacy increase the risk for metabolic syndrome?
Schizophr. Res.
(2007) - et al.
Weight change on aripiprazole-clozapine combination in schizophrenic patients with weight gain and suboptimal response on clozapine: 16-week double-blind study
Eur. Psychiatry
(2008) - et al.
Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis
Lancet
(2012) - et al.
Drug utilization patterns and outcomes associated with in-hospital treatment with risperidone or olanzapine
Clin. Ther.
(1998) - et al.
Combination of amisulpride and olanzapine in treatment-resistant schizophrenic psychoses
Eur. Psychiatry
(2004) - et al.
Amisulpride augmentation in patients with schizophrenia partially responsive or unresponsive to clozapine. A randomized, double-blind, placebo-controlled trial
Pharmacopsychiatry
(2008) Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology
J. Psychopharmacol.
(2011)
Olanzapine: a systematic review and meta-regression of the relationships between dose, plasma concentration, receptor occupancy, and response
J. Clin. Psychopharmacol.
The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements
Schizophr. Bull.
Combination therapy with non-clozapine atypical antipsychotic medication: a review of current evidence
J. Psychopharmacol.
Compliance with medication regimens for mental and physical disorders
Psychiatr. Serv.
Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics
BMC Psychiatry
Incidence of schizophrenia and other psychoses in ethnic minority groups: results from the MRC AESOP Study
Psychol. Med.
Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial
Int. J. Neuropsychopharmacol.
Prevalence, trends, and factors associated with antipsychotic polypharmacy among Medicaid-eligible schizophrenia patients, 1998–2000
J. Clin. Psychiatry
An audit of outpatient antipsychotic usage in the three health sectors of Auckland, New Zealand
Aust. N. Z. J. Psychiatry
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