Prescribing of clozapine and olanzapine: dosage, polypharmacy and patient ethnicity

AIMS AND METHOD

The aim of this study was to determine the existence and extentof differences in prescribing practice for patients accordingto ethnic group, with two widely used atypical antipsychotics,olanzapine and clozapine. All in-patient prescription chartswere screened and patients receiving olanzapine and clozapineidentified. Dosage, antipsychotic co-prescription and race were recorded, along with demographic details, and evaluated usingcomparative statistical analysis.

RESULTS

Overall, 1441 prescriptions were screened; 328 patients receivedolanzapine and 200 clozapine. Details of ethnic origin wereavailable for 287 of those prescribed olanzapine and 188 ofthose prescribed clozapine. There was no significant differencebetween ethnic groups in age or gender, for either drug. Forclozapine, dosage and extent of antipsychotic co-prescriptiondid not differ significantly between ethnic groups; for olanzapine,there was no significant difference in daily dose between thegroups, but co-prescription was significantly more common inBlack (33%) than in White patients (20%; P=0.023).

CLINICAL IMPLICATIONS

Important differences in the prescription of olanzapine andclozapine between ethnic groups are uncommon, but demand furtherinvestigation. Larger studies incorporating additional baselinedetails such as diagnosis and body weight are called for.

Introduction

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Introduction

Ethnicity is an important influence on the drug treatment ofpsychosis and schizophrenia. Two major factors have been noted (Bhugra & Bhui, 1999); the various interpretations ofculturally influenced behaviours, and their effect on treatmentchoice and dosage; and the variation in drug dosage that arises as a consequence of the different metabolic capacities foundin different racial groups.

Differences in therapeutic dosage between races have been notedfor several antipsychotic drugs. For example, the therapeuticdosage of chlorpromazine in Asian patients appears to be aroundhalf that needed in White patients (Lin & Finder, 1983).The therapeutic dosage of haloperidol also seems to be lowerin Asian than in White patients (Lin et al, 1989), probablybecause of reduced metabolic capacity in Asian people (Chang et al, 1991;Zhang-Wong et al, 1998). In fact, haloperidolmetabolism has been shown to be different in White, Chinese,Hispanic and Black populations (Jann et al, 1993).

For clozapine, racial differences in metabolism have been notedfor White compared with Chinese patients (Farooq, 1998; Chong,1998). Differences in response to clozapine have been reportedin Korean Americans and Caucasians (Matsuda et al, 1996), differenceswhich may have been a result of different pharmacokinetics, pharmacodynamics, or both (Masellis et al, 2000). Also, clozapine-relatedagranulocytosis may be more common in Asians than in Whites (Munro et al, 1999). With olanzapine, no report of raciallydetermined differences in dosage, response or metabolism couldbe found. There is no report of variation in antipsychoticco-prescription according to race for clozapine or olanzapine.

This study was designed as a pilot investigation of the existenceand extent of differences in rates of polypharmacy and in dosageof clozapine and olanzapine according to ethnic origin.

Method

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Method

In February 2002, all in-patient prescription charts in theSouth London and Maudsley National Health Service (NHS) Trustwere examined, and patients prescribed clozapine and olanzapinewere identified. For these patients, prescribed dosage wasrecorded and the medical notes were examined to determine patients’documented ethnic origin. Ethnic group was categorised underthe following headings: White; Black (Black Caribbean, Black African and Black other); Asian (Indian, Pakistani, Bangladeshi,Chinese, other Asian); and Unknown (i.e. not recorded in notes).All other drugs prescribed were also recorded, as was patientgender and age. Data were analysed using the Statistical Packagefor the Social Sciences version 7, for Windows.

Results

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Results

A total of 1441 prescriptions were screened. Of these, 328 werefor olanzapine and 200 for clozapine. Ethnic grouping couldbe determined for 287 patients prescribed olanzapine and 188prescribed clozapine.

An analysis of patient demographic characteristics is givenin Table 1. Results of the statistical analysis for clozapinewere: age, univariate analysis of variance (ANOVA), d.f.=2,P=0.41; gender, ${chi}$ ²=1.26, d.f.=2, P>0.5. For olanzapine, resultswere: age, (ANOVA), d.f.=2, P=0.27; gender, ${chi}$ ²=1.41, d.f.=2,P>0.1. There was no significant difference between ethnicgroups in age or gender for either drug.

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Table 1. Demographic characteristics of the patients studied

Dosage
The mean recorded daily dosages for clozapine are shown in Table 2,and those for olanzapine are given in Table 3. Neitherdrug showed any significant difference in dosage accordingto race.

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Table 2. Clozapine dosage

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Table 3. Olanzapine dosage

Co-prescription with other antipsychotic drugs
The rates of co-prescription with other antipsychotic drugsare shown in Table 4 for clozapine and in Table 5 for olanzapine.There was no significant difference in rates of co-prescriptionaccording to ethnicity for clozapine, but for olanzapine, Whitepatients were significantly less likely than Black patientsto be co-prescribed regular antipsychotics (P=0.023).

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Table 4. Clozapine co-prescription rates

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Table 5. Olanzapine co-prescription rates

Discussion

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Discussion

This pilot study revealed only one difference in prescribingvariables that might be related to ethnic origin: antipsychoticpolypharmacy was more common in Black patients than in Whitepatients in those receiving olanzapine. All other parameterssuggested no important or significant difference between ethnicgroups.

These results suggest that there are few important differencesrelated to patient ethnicity in prescribing practice for clozapineand olanzapine. However, the study had two major shortcomings.First, the sample size was limited by the availability of patientsand of data relating to patients. This meant that the study’spower to detect differences - should they have existed - wassomewhat limited. This is particularly true for comparisons involving Asian patients, for whom differences were often substantialbut the small number of patients meant that such differenceswere not statistically significant. Second, diagnosis was notrecorded. Diagnosis is likely to have an important effect onprescribing practice, and so the absence of diagnostic datato some extent diminishes the validity of results obtained.These two observations make precise interpretation difficult.Nevertheless, the absence of any clear difference in dosageprescribed for White and Black patients strongly suggests thattheir ethnicity did not play a part in prescribing decisionsin this regard.

The observation that polypharmacy with olanzapine and otherantipsychotic drugs was more common in Black than in Whitepatients requires further investigation. It is also noteworthythat there was something of a trend for higher dosage to beused in Black patients; further study is required to expandon these preliminary observations. Such studies should involvelarger numbers of participants, and also should record otherinfluences on prescribing, such as diagnosis, body weight andhistory of illness or violence.

References

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