Olanzapine-Induced Weight Gain in Patients With First-Episode Schizophrenia: A Double-Blind, Placebo-Controlled Study of Fluoxetine Addition

OBJECTIVE: Since olanzapine-induced weight gain may be attributable to the antagonistic activity of olanzapine at the serotonin-2C receptor, the authors hypothesized that it might be attenuated by addition of the selective serotonin reuptake inhibitor fluoxetine. METHOD: First-episode hospitalized schizophrenia patients (N=30) were randomly assigned in an 8-week double-blind study of olanzapine, 10 mg/day, coadministered with either fluoxetine, 20 mg/day (N=15), or placebo (N=15). RESULTS: The group receiving olanzapine plus fluoxetine showed significantly less improvement in positive and disorganized symptom dimensions than the group receiving olanzapine plus placebo. The two groups demonstrated similar and substantial gradual weight gains. CONCLUSIONS: These results suggest that fluoxetine coadministration is clinically ineffective and cannot attenuate olanzapine-induced weight gain.