Prescribing clozapine in the UK: Quality improvement issues identified by clinical audit.

INTRODUCTION: The Prescribing Observatory for Mental Health initiated a quality improvement (QI) programme on clozapine use in UK mental health services. METHODS: Clinical audits conducted in 2019 and 2021. RESULTS: Sixty-three participating NHS Trusts/healthcare organisations in 2019, and 61 in 2021, submitted treatment data for 6948 and 8155 patients, respectively. In both audits, high-dose and/or combined antipsychotic medications had been prescribed immediately before initiating clozapine in over a quarter of patients recently started on clozapine. In patients who were tobacco smokers and recently discharged from a smoke-free ward, the impact of the potential change in smoking status had been considered in the care plans of just under one-third in 2019 and just over a half in 2021. For community patients, their Summary Care Records (SCRs) included their clozapine prescriptions in 58% of cases in 2019 and 72% in 2021. CONCLUSIONS: Three QI issues were identified. (1) Antipsychotic regimens with limited evidence for efficacy in treatment-resistant schizophrenia were prescribed for over a quarter of cases before starting clozapine. Use of such strategies may delay clozapine treatment, potentially reducing the likelihood of a therapeutic response. (2) While anticipation of the consequences of a change in smoking status on plasma clozapine concentration following discharge from hospital showed improvement over time, even in 2021 it was not evident for nearly a half of relevant cases. (3) While inclusion of clozapine in the SCR also improved over time, even in 2021 it was missing for more than a quarter of community patients.

Lamotrigine for people with borderline personality disorder: a RCT.

BACKGROUND: No drug treatments are currently licensed for the treatment of borderline personality disorder (BPD). Despite this, people with this condition are frequently prescribed psychotropic medications and often with considerable polypharmacy. Preliminary studies have indicated that mood stabilisers may be of benefit to people with BPD. OBJECTIVE: To examine the clinical effectiveness and cost-effectiveness of lamotrigine for people with BPD. DESIGN: A two-arm, double-blind, placebo-controlled individually randomised trial of lamotrigine versus placebo. Participants were randomised via an independent and remote web-based service using permuted blocks and stratified by study centre, the severity of personality disorder and the extent of hypomanic symptoms. SETTING: Secondary care NHS mental health services in six centres in England. PARTICIPANTS: Potential participants had to be aged ≥ 18 years, meet diagnostic criteria for BPD and provide written informed consent. We excluded people with coexisting psychosis or bipolar affective disorder, those already taking a mood stabiliser, those who spoke insufficient English to complete the baseline assessment and women who were pregnant or contemplating becoming pregnant. INTERVENTIONS: Up to 200 mg of lamotrigine per day or an inert placebo. Women taking combined oral contraceptives were prescribed up to 400 mg of trial medication per day. MAIN OUTCOME MEASURES: Outcomes were assessed at 12, 24 and 52 weeks after randomisation. The primary outcome was the total score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. The secondary outcomes were depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment and adverse events. Higher scores on all measures indicate poorer outcomes. RESULTS: Between July 2013 and October 2015 we randomised 276 participants, of whom 195 (70.6%) were followed up 52 weeks later. At 52 weeks, 49 (36%) of those participants prescribed lamotrigine and 58 (42%) of those prescribed placebo were taking it. At 52 weeks, the mean total ZAN-BPD score was 11.3 [standard deviation (SD) 6.6] among those participants randomised to lamotrigine and 11.5 (SD 7.7) among those participants randomised to placebo (adjusted mean difference 0.1, 95% CI -1.8 to 2.0; p = 0.91). No statistically significant differences in secondary outcomes were seen at any time. Adjusted costs of direct care for those prescribed lamotrigine were similar to those prescribed placebo. LIMITATIONS: Levels of adherence in this pragmatic trial were low, but greater adherence was not associated with better mental health. CONCLUSIONS: The addition of lamotrigine to the usual care of people with BPD was not found to be clinically effective or provide a cost-effective use of resources. FUTURE WORK: Future research into the treatment of BPD should focus on improving the evidence base for the clinical effectiveness and cost-effectiveness of non-pharmacological treatments to help policy-makers make better decisions about investing in specialist treatment services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN90916365. FUNDING: Funding for this trial was provided by the Health Technology Assessment programme of the National Institute for Health Research (NIHR) and will be published in full in Health Technology Assessment; Vol. 22, No. 17. See the NIHR Journals Library website for further project information. The Imperial Biomedical Research Centre Facility, which is funded by NIHR, also provided support that has contributed to the research results reported within this paper. Part of Richard Morriss' salary during the project was paid by NIHR Collaboration for Leadership in Applied Health Research and Care East Midlands.

Antipsychotic polypharmacy in schizophrenia: benefits and risks.

Antipsychotic polypharmacy refers to the co-prescription of more than one antipsychotic drug for an individual patient. Surveys of prescribing in psychiatric services internationally have identified the relatively frequent and consistent use of combined antipsychotics, usually for people with established schizophrenia, with a prevalence of up to 50% in some clinical settings. A common reason for prescribing more than one antipsychotic is to gain a greater or more rapid therapeutic response than has been achieved with antipsychotic monotherapy. However, the evidence on the risks and benefits for such a strategy is equivocal, and not generally considered adequate to warrant a recommendation for its use in routine clinical practice in psychiatry. Combined antipsychotics are a major contributor to high-dose prescribing, associated with an increased adverse effect burden, and of limited value in helping to establish the optimum maintenance regimen for a patient. The relatively widespread use of antipsychotic polypharmacy identified in cross-sectional surveys reflects not only the addition of a second antipsychotic to boost therapeutic response, but also the use of as-required antipsychotic medication (mainly to treat disturbed behaviour), gradual cross-titration while switching from one antipsychotic to another, and augmentation of clozapine with a second antipsychotic where the illness has failed to respond adequately to an optimized trial of clozapine. This review addresses the clinical trial data and other evidence for each of these pharmacological approaches. Also reviewed are examples of systematic, practice-based interventions designed to reduce the prevalence of antipsychotic polypharmacy, most of which have met with only modest success. Guidelines generally agree that if combined antipsychotics are prescribed to treat refractory psychotic illness, this should be after other, evidence-based, pharmacological treatments such as clozapine have been exhausted. Further, their prescription for each patient should be in the context of an individual trial, with monitoring of the clinical response and adverse effects, and appropriate physical health monitoring.

Ethical dilemmas: should antipsychotics ever be prescribed for people with dementia?

The use of antipsychotics for the treatment of behavioural and psychological symptoms of dementia (BPSD) is controversial. Antipsychotics cause harm and evidence-based guidelines advise against their use. We argue that antipsychotics may be justified using a palliative model: by reducing severe distress in those whose life expectancy is short.

A UK audit of screening for the metabolic side effects of antipsychotics in community patients.

Reviews of the association between psychotic disorder, the metabolic syndrome, diabetes, and antipsychotic drugs conclude that there is a need for active, routine physical health screening of patients' prescribed antipsychotic drugs. From published guidelines, we derived the audit standard that all such patients should, as a minimum, have their blood pressure, body mass index (BMI) (or other measure of obesity such as waist circumference), blood glucose (or HbA(1c)), and plasma lipids measured at least once a year. We conducted an audit of the clinical records of 1966 eligible patients under the care of 48 multidisciplinary, assertive outreach clinical teams in 21 mental health services across the United Kingdom. This revealed a recorded measurement within the previous year for blood pressure in 26% of the patients, obesity in 17%, blood glucose (or HbA(1c)) in 28% and plasma lipids in 22%, with all 4 measures documented in 11%. In the total national sample, 6% had a documented diagnosis of diabetes, 6% hypertension, and 6% dyslipidemia. Extrapolating from the prevalence of these disorders in similar populations suggests that for every patient with a known diagnosis of diabetes, another had not been recognized, for every known case of hypertension, 4 had been missed, and for every known case of dyslipidemia, 7 had been missed. The responses of the clinical teams to a questionnaire yielded information on obstacles to screening in routine practice, revealing uncertainty about whose responsibility this was, a lack of confidence about the interpretation of abnormal screening results, and limited access to basic equipment.

Testing for diabetes in hospitalised patients prescribed antipsychotic drugs.

BACKGROUND: Studies using computer databases suggest that atypical antipsychotic agents are more likely to be associated with diabetes than are conventional drugs. AIMS: To discover the extent of testing for diabetes mellitus in hospital in-patients prescribed antipsychotics. METHOD: Prescription charts were screened to identify patients prescribed antipsychotics. Case notes were then searched for evidence of testing for diabetes. RESULTS: In all, 606 patients were prescribed antipsychotics, of whom 250 (41.3%) had evidence of prior testing for diabetes. Patients prescribed atypicals were 40% more likely to have been tested than those prescribed conventional drugs (RR =1.4,95% CI1.1-1.9). Adjusted odds ratios v. conventional antipsychotics for conventional antipsychotics for testing were significantly higher for clozapine (OR=4.64,95% CI 2.42-8.90), olanzapine (OR=1.85,95% CI1.04-3.30) and antipsychotic polypharmacy (OR=2.96,95% CI1.59-5.52). CONCLUSIONS: Testing for diabetes was undertaken in less than half of the patients studied. Testing was more common in those receiving atypical antipsychotics. Apparent differences in claimed causal association of the use of some antipsychotics with diabetes may in part reflect different rates of testing.

Patterns of antipsychotic and anticholinergic prescribing for hospital inpatients.

The development of atypical antipsychotics has not only given the prescriber more options, but also increased the complexity of decision making. We examined current prescribing practice for antipsychotic and anticholinergic drugs, which involved a 1-day census of all antipsychotic and anticholinergic drugs prescribed for 4191 inpatients in 49 UK mental health services. Eighty-five percent of inpatients were prescribed antipsychotics, 48% of whom were prescribed more than one. Atypical antipsychotics were widely prescribed and combined with typicals in over 60% of cases. Large doses of antipsychotics were frequently prescribed 'as required'. The dose administered was always much less than the dose prescribed and nothing at all was administered against 79% of prescriptions. Antipsychotic prescribing often deviates from recommended practice. Nursing staff have considerable discretion to administer large doses of antipsychotics on an 'as required' basis.

Prior antipsychotic prescribing in patients currently receiving clozapine: a case note review.

BACKGROUND: Clozapine is indicated for the treatment of resistant schizophrenia, which is usually defined as failure to respond to adequate trials of 2 antipsychotics. It is thought that only clozapine is likely to be effective in such cases and that other drugs are ineffective. We sought to discover prior patterns of antipsychotic prescribing in schizophrenic patients eventually prescribed clozapine. METHOD: Prescribing histories were obtained from prescription charts and case notes for all inpatients prescribed clozapine in 4 hospitals in southeast London during April 2001. RESULTS: 120 patients were identified, of whom 112 had been diagnosed with schizophrenia or schizoaffective disorder and whose data were analyzed. The mean duration of illness was 15.1 years. Subjects had experienced a mean of 9.2 (range, 2-35) episodes of antipsychotic prescription before clozapine was first used, with 5.7 (range, 0-25) episodes constituting adequate trials (drug used at therapeutic dose for 6 weeks). The mean number of different antipsychotics used was 5.5 (range, 1-13), with a mean of 4.0 (range, 0-12) given an adequate trial. Ninety percent of patients (N = 101) had received an atypical antipsychotic before first use of clozapine, and 65% (N = 73) had previously received antipsychotic polypharmacy. The mean maximum theoretical delay in using clozapine was 5.0 years (range, 0-11.1 years). Longer delay was significantly (p <.05) associated with being aged over 30 years at the time of the study, being diagnosed with psychotic illness before the introduction of clozapine, and completing adequate trials of 2 different antipsychotics before the introduction of clozapine or risperidone. CONCLUSION: Clozapine treatment was quite likely delayed for longer than is clinically desirable. This delay may have important effects on quality of life, clinical outcome, and health resource utilization.