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Objective: The aim of this study was to test whether the initial antipsychotic response to clozapine is related to subsequent weight change. Method: This study was an 8-year retrospective chart review of 96 hospitalized patients with schizophrenia. Data on monthly weight change, initial clinical response, age, gender, clozapine dose, and concomitant use of mood stabilizers and other antipsychotics were analyzed. Results: Fifty-five (57.3%) of the patients received clozapine over the entire 8-year period; these subjects experienced an average weight gain of 11.7 kg (SD=1.6). Seventeen of these patients (30.9%) who had a significant initial clinical response (CGI improvement rating of 1 or 2 during the first 14 months) gained significantly more weight (13.8 kg [SD=8.4]) than did the 38 patients without a significant initial response (4.5 kg [SD=12.0]). Multiple linear regression analysis showed significant initial clinical response and lower baseline body mass index were associated with significantly more weight gain. Conclusions: The results show that initial antipsychotic response to clozapine is associated with subsequent long-term weight gain as measured over 8 years.