Treatment of weight gain with fluoxetine in olanzapine-treated schizophrenic outpatients

Significant weight gain is a side effect associated with olanzapine treatment in some patients. We investigated the efficacy of high-dose fluoxetine as a weight-reducing agent for patients who develop early weight gain with olanzapine treatment. Patients that gained >/=3% of their baseline weight in the initial 8 weeks of olanzapine treatment (n=31) were randomized to double-blind treatment with placebo or fluoxetine (60 mg/day). Clinical, weight, and weight-related measures were assessed. Fluoxetine failed to demonstrate weight-reducing effects (fluoxetine group: baseline mean 80.5 kg, SD=19.1, last mean=83.5 kg, SD=19.8; placebo group: baseline mean=77.1 kg, SD=12.1, last mean=78.8 kg, SD=10.6; F=1.3; df=1, 18; p=0.3). There were no differential effects in psychopathology, extrapyramidal side effects or weight-related measures between the placebo and fluoxetine groups. Serotonin reuptake inhibitors are probably not a practical option to counteract weight gain induced by atypical antipsychotics. Atypical-induced weight gain may result from mechanisms other than 5HT reuptake blockade.