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Treatment of clozapine-associated weight gain: a systematic review

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Abstract

Purpose

Clozapine is an antipsychotic drug with superior efficacy in treatment-resistant schizophrenia. Clozapine is associated with a low likelihood of extrapyramidal symptoms and other neurological side-effects but a high propensity to induce weight gain and general metabolic dysregulation. Various pharmacological and behavioral treatment approaches for reducing clozapine-associated weight gain exist in the literature; however, there are currently no clear clinical guidelines as to which method is preferred. The aim of the current review is to systematically summarize studies that have studied both pharmacological and non-pharmacological interventions to attenuate or reverse clozapine-associated weight gain.

Methods

A systematic review of EMBASE and MEDLINE databases of all articles published prior to January 2014 was conducted. Seventeen studies were identified as meeting inclusion criteria and included in the review.

Results

Aripiprazole, fluvoxamine, metformin, and topiramate appear to be beneficial; however, available data are limited to between one and three randomized controlled trials per intervention. Orlistat shows beneficial effects, but in males only. Behavioral and nutritional interventions also show modest effects on decreasing clozapine-associated weight gain, although only a small number of such studies exist.

Conclusions

While a number of pharmacological interventions can produce modest weight loss, each may be associated with negative side effects, which should be considered before beginning treatment. Given the pressing need to improve cardiometabolic health in most clozapine-treated patients, substantially more research is needed to develop sound clinical practice guidelines for the treatment of clozapine-associated weight gain.

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Funding

Support for the current manuscript was provided by the Natural Sciences and Engineering Research Council of Canada grant 356069-09 to AMB, and by the British Columbia Provincial Health Services Authority.

Conflict of interest

Dr. Procyshyn is a paid consultant for and is on the speaker’s bureau for AstraZeneca, Bristol-Myers Squibb, Janssen, Otsuka, Pfizer, and Sunovion. Dr. Barr has received funding support from Bristol-Myers Squibb. The other authors declare that they have no conflict of interest.

Contribution of Authors

The literature was reviewed by ZW. All authors contributed to the writing and final review of the manuscript.

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Authors and Affiliations

  1. Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada

    Z. Whitney & A. M. Barr

  2. British Columbia Mental Health and Addictions Research Institute, Translational Research Building 3rd Floor 938 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada

    R. M. Procyshyn & A. M. Barr

  3. Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada

    R. M. Procyshyn & D. H. Fredrikson

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  1. Z. Whitney
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  2. R. M. Procyshyn
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  4. A. M. Barr
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Correspondence to A. M. Barr.

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Whitney, Z., Procyshyn, R.M., Fredrikson, D.H. et al. Treatment of clozapine-associated weight gain: a systematic review. Eur J Clin Pharmacol 71, 389–401 (2015). https://doi.org/10.1007/s00228-015-1807-1

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  • DOI: https://doi.org/10.1007/s00228-015-1807-1

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