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Schizophrenia Bulletin 2000 26(2):421-440;
© 2000 by Oxford University Press and the Maryland Psychiatric Research Center (MPRC)
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© Oxford University Press

Clozapine Augmentation: Safety and Efficacy

Siow-Ann Chong, M.B.B.S., M.Med.Psych., Associate Consultant and Gary Remington, M.D., Ph.D., F.R.C.P.(C)
Woodbridge Hospital and Institute of Mental Health Singapore
Director of the Medication Assessment Program for Schizophrenia at the Centre for Addiction and Mental Health, Clarke Division, and Associate Professor, University of Toronto Toronto, Canada

Send reprint requests to Dr. G. Remington, Centre for Addiction and Mental Health, Clarke Institute, Schizophrenia Division, Toronto, Ontario M5T 1R8, Canada; e-mail: gary_remington{at}camh.net

While clozapine has been demonstrated to be efficacious in refractory schizophrenia and possibly schizoaffective as well as bipolar disorders, a substantial number of patients still remain unresponsive. One strategy in treating these refractory patients is to augment clozapine with other somatic treatments. This article reviews the efficacy and safety of the combination of clozapine with other somatic treatments. A total of 70 articles were obtained from a manual, as well as computerized (Medline), search of the English language literature from 1978 to March 1998. Few controlled studies exist; most were case reports/series. From these data, the greatest risk of adverse effects seems to be associated with clozapine combined with benzodiazepines, valproate, or lithium, but no currently evaluated combination is absolutely unsafe. In terms of efficacy, the data suggest a number of potential augmentation strategies, although controlled data are few. Combination therapies with clozapine are common in clinical practice, despite a lack of empirical data, and the benefits and risks of these combinations need to be systematically reviewed.

Keywords: Clozapine / augmentation / combination


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