Treatment of clozapine-associated weight gain: a systematic review.

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.

An open comparison of clozapine and risperidone in treatment-resistant schizophrenia.

BACKGROUND: Clozapine and risperidone are used in treatment-resistant schizophrenia. At present, there are few reported comparisons of these drugs in this population. We report on a consecutive series of treatment-resistant schizophrenics given either clozapine or risperidone in open clinical trials. METHOD: Subjects were treated with clozapine (n = 57) or risperidone (n = 29). Pretreatment GAF, CGI, and PANSS scores did not differ between the groups, nor did demographic variables including age, age at first hospitalization, years ill, number of previous hospitalizations, or gender. The mean treatment trial was 12.1 weeks, with mean doses of clozapine 420 mg, and risperidone 7.75 mg. The length of the trial did not differ significantly between the groups. Response was taken to be a 20% decrease in the PANSS score. RESULTS: Using repeated measures ANOVA, PANSS total scores (F = 5.3, p = 0.02) and positive subscore (F = 7.4, p = 0.008) showed greater improvement in the clozapine group than the risperidone group, while other PANSS subscores showed a trend toward greater improvement with clozapine. The PANSS-derived factors of excitement (F = 6.7, p = 0.01), psychosocial withdrawal (F = 3.8, p = 0.05), and psychomotor retardation (F = 3.9, p = 0.05) improved more in the group treated with clozapine. The GAF (F = 10.9, p = 0.0014), CGI (F = 11.5, p = 0.0011), and CGI improvement (p = 0.0001) scores also improved more in the clozapine group. Of the clozapine group, 25 (44%) responded, while 8 (28%) of the risperidone group responded to treatment. DISCUSSION: Clozapine had better efficacy in subjects with treatment-resistant schizophrenia compared to risperidone, although risperidone appears to yield better response rates than those previously reported for typical antipsychotics. Double-blind, controlled trials of risperidone are needed to establish its efficacy in treatment-resistant schizophrenia.