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The metabolic side effects of clozapine are prominent (Henderson 2001; D. A. Wirshing et al. 1998, 1999). Weight gain has been observed in both premarketing and postmarketing trials (Henderson 2001; Simpson and Varga 1974). In patients observed in various clinical trials in our laboratory, the average weight gain in a 6-month period with clozapine treatment was 6.9 ± 0.8 kg. Allison et al. (1999) performed a meta-analysis of the weight-gain data in short-term trials of medications. The average weight gain observed with clozapine was 4.45 kg, which exceeded the weight gain observed with all of the other medications in the study, including the conventional agent thioridazine (3.19 kg), a medication known for its weight-gain liability. The weight gain observed with clozapine seems to occur for a prolonged period of time—up to 40 weeks. In one naturalistic study, Henderson (2001) observed patients in a clozapine clinic for 5 years and noted weight gain occurring for up to 46 months in some patients.

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