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An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels

Ng, Chee H.a; Chong, Siow-Annb; Lambert, Tima; Fan, Agnesa; Peter Hackett, L.c; Mahendran, Rathib; Subramaniam, Mythilyb; Schweitzer, Isaaca

International Clinical Psychopharmacology: May 2005 - Volume 20 - Issue 3 - p 163-168

The present study investigated clozapine dosage, plasma clozapine and metabolite levels, clinical and side-effect profiles in Asian versus Caucasian patients with chronic schizophrenia who were on stable maintenance treatment. Twenty Asian patients from Singapore and 20 Caucasian patients from Australia were systematically evaluated with the following rating scales: Positive and Negative Syndrome Scale for Schizophrenia, drug attitude scale (DAI-10), drug adverse reaction profile (Liverpool University Neuroleptic Side-effect Rating Scale), extrapyramidal side-effects scales (Abnormal Involuntary Movement Scale, Simpson and Angus Scale). Cigarette and caffeine consumption were recorded and steady-state plasma clozapine and metabolites levels were measured. Although Asian patients received a significantly lower mean clozapine dose (176 mg/day) than the Caucasian group (433 mg/day, P<0.001), plasma clozapine levels were similar between the groups. As a result, Asian patients had more than twice the effective clozapine concentration to dose ratio (P<0.001). The findings remained significant even after controlling for gender, body mass index, cigarette, alcohol and caffeine use. Conversely, the plasma metabolites (desmethylclozapine and clozapine N-oxide) to clozapine ratios were higher in the Caucasian patients (P<0.01). Compared to Caucasian patients, Asian patients appeared to have a lower dosage requirement for clinical efficacy. Hence, appropriate dose adjustment should be considered in Asian patients receiving maintenance clozapine therapy in clinical practice.

aDepartment of Psychiatry, University of Melbourne, Richmond, Australia

bInstitute of Mental Health, Woodbridge Hospital, Buangkok View, Singapore

cWestern Australian Centre for Pathology and Medical Research, Nedlands, Australia

Correspondence and requests for reprints to Dr Chee Ng, Department of Psychiatry, University of Melbourne, The Melbourne Clinic, 130 Church Street, Richmond 3121, Victoria, Australia

Tel: +61 03 9420 9350; fax: +61 03 9428 5990;


Received 15 November 2004 Accepted 24 February 2005

© 2005 Lippincott Williams & Wilkins, Inc.