Novel antipsychotics: Comparison of weight gain liabilities

Background: We performed a retrospective analysis of 122 clinical records o f 92 male patients with DSM-III-R schizophrenia to examine the relative wei ght gain liabilities of clozapine, risperidone, olanzapine, and sertindole compared with haloperidol. We hypothesized that the unique pharmacodynamic profiles of these agents would contribute to different amounts and patterns of weight gain. Method: Data were analyzed to determine differences in weight gain during t reatment among patients receiving 5 different drug treatments (clozapine [N = 20], olanzapine [N = 13], risperidone [N = 38], haloperidol [N = 43], an d sertindole [N = 8]). Measures of maximal weight gain, final weight, and d uration to maximal weight gain were calculated. Results: Repeated measures analyses of variance controlling for age, treatm ent duration, and initial weight revealed statistically significant differe nces between groups on all 3 measures. Clozapine and olanzapine had the gre atest maximal weight gain liability (F = 4.13, df = 4,23; p = .01). Weight gain with clozapine, but not olanzapine or risperidone, appears to persist (as reflected by final weight) despite behavioral interventions (e.g., nutr itional consultation, suggested exercise regimen; F = 5.69, df = 4,23; p = .003). Clozapine- and olanzapine-treated subjects appeared to gain weight o ver a prolonged period of time, whereas risperidone and sertindole-treated subjects had a more limited period of weight gain (F = 2.95, df = 4,25; P = .04). Conclusion: Clozapine and olanzapine caused the most weight gain, risperido ne was intermediate, and sertindole had less associated weight gain than ha loperidol. The relative receptor affinities of the novel antipsychotics for histamine H-1 appear to be the most robust correlate of these clinical fin dings.