Audit of metabolic syndrome in adults prescribed clozapine in community and long-stay in-patient populations

AIMS AND METHODS

To calculate the prevalence of metabolic syndrome in patientsreceiving clozapine in community and long-stay in-patient settings.Patients were assessed using measures specified by the ExpertPanel of the US National Cholesterol Education Program.

RESULTS

The prevalence of the metabolic syndrome was calculated as 53%in the community groups and 11% in the in-patient group, althoughboth sample sizes (particularly the in-patient group) weresmall. Women were more frequently affected than men in thecommunity population.

CLINICAL IMPLICATIONS

The higher percentage of metabolic syndrome in the communitypatients receiving clozapine has implications with respectto physical health. The reasons for the lower percentage inthe in-patient group are unclear. Our findings point to a possibledifference in the physical health of long-stay psychiatricin-patients and patients in the community.

Introduction

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Introduction

The term ‘metabolic syndrome’ refers to a numberof risk factors associated with the development of coronaryheart disease, one of the biggest causes of morbidity and mortalityin the Western world (Lakka et al, 2002). There are variousdefinitions of metabolic syndrome but all have in common centralobesity, impaired glucose tolerance, hypertriglyceridaemia, hypercholesterolaemia and hypertension. Patients with metabolicsyndrome can expect to have a two-fold to three-fold increasein mortality due to coronary heart disease (Lakka et al, 2002).Various studies have identified increased mortality as a resultof coronary heart disease in schizophrenia, and explanationsfor this have included cigarette smoking, poor diet and lackof exercise (Brown, 1997). Since the mid-1990s an accumulatingevidence base has identified treatment with antipsychotic medicationas an additional risk factor (Newcomer, 2005).

Clozapine is a dibenzodiazepine-class antipsychotic, which hasa receptor affinity profile unique among the antipsychoticmedications currently available and has a singular place inthe treatment of treatment-resistant schizophrenia. It is theonly antipsychotic of proven efficacy in treatment-resistantschizophrenia (Kane et al, 1988) and evidence also exists tosupport the reduction in risk of suicide in patients takingclozapine. Clozapine therefore maintains a potentially uniqueposition in the treatment of schizophrenia.

There is evidence linking clozapine to the development of dyslipidaemia, weight gain and obesity, glucose intolerance and diabetes,and hypertension (Newcomer, 2005). Accumulating evidence suggeststhat clozapine has a marked effect on various metabolic parameterswhen compared with other antipsychotics (American Diabetes Association et al, 2004;British Medical Association & Royal Pharmaceutical Society of Great Britain, 2006;Lamberti et al, 2006). One study attempted to calculate theprevalence of metabolic syndrome in a population prescribedclozapine and identified the syndrome in 50 out of 93 patients(54%) (Lamberti et al, 2006). No estimate has been performedin a community setting in the UK and none has studied long-termin-patient populations.

Method

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Method

For the purposes of calculating the prevalence of metabolicsyndrome in this audit, the National Cholesterol EducationProgram Adult Treatment Panel III guidelines (Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, 2001)were used (Table 1). The presence of three out of the fivemeasurements in Table 1 is necessary to identify the syndrome.

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Table 1. Adult Treatment Panel III guidelines for the detection of metabolic syndrome

The sample comprised all patients in receipt of clozapine underthe care of the Ammanford and Carmarthen community mental healthteams (CMHTs) and the continuing care in-patient unit in Carmarthen,and were identified from the central pharmacy records. TheAmmanford and Carmarthen teams are multidisciplinary and covera total population of approximately 80 000. The continuingcare in-patient unit has predominantly long-stay patients, subsequentto the closure of an asylum (St David’s Hospital, Carmarthen).The catchment areas are a mix of former industrial and rural areas of Carmarthenshire in south-west Wales and have pocketsof socio-economic deprivation. The CMHTs have been runningclozapine clinics for a number of years; these clinics aremanaged by dedicated community psychiatric nurses and pharmacists.

The audit was performed to compare the prevalence of metabolicsyndrome in our populations with that identified in a previousstudy (Lamberti et al, 2006). All patients were routinelyoffered the physical investigations detailed in Table 1, andthese investigations were undertaken by a member of the studyteam using standardised procedures. Such assessments were undertakenin the clozapine clinics at the CMHT bases for the communitypatients, and in the continuing care unit for the in-patients.The duration of clozapine treatment and current dose for eachpatient were ascertained by checking the register of the pharmacydepartment.

Results

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Results

A total of 52 patients were prescribed clozapine, all of whomwere under the care of the clozapine clinics or were long-stayin-patients. The populations were analysed independently. Inthe community groups (mean dose of clozapine 385 mg) therewere 32 male patients (age range 26-62 years, mean 44 years;duration of treatment 8-204 months, mean 90 months) and 11 female patients (age range 23-69 years, mean 47 years; duration oftreatment 16-192 months, mean 100 months). In the in-patientpopulation (mean dose of clozapine 456 mg) there were 5 malepatients (age range 49-73 years, mean 59 years; duration oftreatment 3-72 months, mean 22 months) and 4 female patients(age range 62-64 years, mean 64 years; duration of treatment4-72 months, mean 32 months). All patients had a recorded diagnosisof treatment-resistant schizophrenia. The physical investigationswere performed over a 3-month period from December 2006 toFebruary 2007.

Complete results of the investigations listed in Table 1 wereobtained for 49 patients (Table 2, Fig. 1). The results were incomplete for 3 patients in the community group. Twenty-three(53%) of the 43 community patients (15 men, 8 women; mean clozapinedose 450 mg) met the criteria for metabolic syndrome, and thereappeared to be an excess among women compared with men. Bothof these findings concurred with those of Lamberti et al (2006).For those among the community group identified as meeting thecriteria for metabolic syndrome, the mean duration of treatmentwas 74 months (60 months for men and 101 months for women);for those in this group who did not fulfil the criteria formetabolic syndrome it was 114 months (122 months for men and68 months for women). In the in-patient population, 1 (11%)of the 9 patients (1 man; dose of clozapine 450 mg) met thecriteria for metabolic syndrome. Mean duration of stay among the in-patient population was 126 months (men 188 months, women47 months), although many of these individuals had spent longperiods as in-patients prior to their admission to the continuing-careward. Total duration of clozapine treatment among the communitygroup was 3980 months (mean 92.6 months) and among the in-patientgroup it was 438 months (mean 48.6 months).

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Table 2. Results

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Fig. 1. Prevalence of metabolic syndrome among the patient groups. CMHT, community health team; rehab, rehabilitation.

Discussion

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Discussion

This medical audit identified a high prevalence of metabolicsyndrome in the community sample, which was consistent witha previous study that specifically examined the prevalenceof metabolic syndrome in people taking clozapine in a communitypopulation (Lamberti et al, 2006).

Carmarthenshire is one of the ten least healthy places to livein the UK, eight of which are in South Wales, an area of theUK with high rates of coronary heart disease and obesity (CACI/TNS, 2006).The high prevalence of metabolic syndrome detected in the communitygroup has serious implications for long-term physical health,in a group whose access to medical care is, in general, knownto be significantly poorer than that of the general population(Disability Rights Commission, 2006). There is evidence thatlifestyle changes can effect greatest change in metabolic syndrome,by altering both diet and exercise levels. For instance, amongpatients taking clozapine, a low glycaemic index diet has beenshown to reduce the blood glucose level (Smith & White, 2004).

Our findings point to a possible difference in the physicalhealth of long-stay psychiatric in-patients and patients inthe community prescribed clozapine. The prevalence observedin the long-stay in-patient group was far lower than in thecommunity groups in this study. The reasons are unclear, althoughthe sample size (especially the in-patient group) was admittedly small. The small size of the in-patient sample population maybe a result of the move away from long-term in-patient careto community care, a change itself perhaps enabled by clozapine(Kane et al, 1988), such that it was not possible to comparean in-patient group of similar size with the community groups.There was a greater total exposure time to clozapine in thecommunity population compared with the in-patient group, whichcould be a reflection of sustained successful community integration.The balance between the risks of exposure to clozapine andthe benefits of community social inclusion is an area as yet unexplored.

This audit cannot distentangle the many confounding variablesthat need to be identified and controlled for, and it is beyondboth the intention and the scope of this study to identifyprecisely what the differences are between the two types ofpatient population. Yet we believe these results identify anarea deserving of further detailed research. The differentialrates may be accounted for by confounding variables such aslength of time treated, dose of clozapine when tested, andcovariance of the factors measured for physical health. However,consideration should also be given to differences in the natureof the care provided to in-patients, who receive regular (andpossibly relatively nutritious) meals, structured daily activitiesincluding regular exercise, and possibly improved access tomedical care. The in-patient group could therefore be considereda captive audience to measures designed to address their physicalhealth.

This audit has highlighted the fact that people treated withclozapine can have serious physical problems, perhaps particularlythose living in the community. In view of the growing evidencebase linking clozapine to the development of metabolic syndrome,monitoring is imperative. Strengthening the physical healthcareprovided in community settings and general health promotionat primary and secondary levels could be an important influence. With respect to patients living in the community, the QualityOutcomes Framework, which is part of the General Medical Servicescontract, places a responsibility for physical monitoring inprimary care. Care coordinators, gateway workers and link workersare ideally placed to interface between primary and secondarycare, and thus are crucial in ensuring the physical healthneeds of community patients are fully met. The potential benefitsto patients, in terms of improvements both in quality of lifeand longevity, are, we believe, quantifiable.

Acknowledgments

We thank Professor Pamela Taylor, Professor of Forensic Psychiatryat Cardiff University, for all her help and assistance. Wealso thank Claire Jones and Gwyn Jones, community psychiatricnurses, and the Pharmacy Department, Hafan Derwen, Parc DewiSant, Carmarthen, for their assistance in collecting the data.

References

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