Attenuation of olanzapine-induced weight gain with reboxetine in patients with schizophrenia: A double-blind, placebo-controlled study

Objective: Since increased norepinephrine availability may account for the weight-reducing effect of appetite suppressants, the authors hypothesized that the addition of the selective norepinephrine reuptake inhibitor reboxetine may prevent or attenuate olanzapine-induced weight gain. Method: Twenty-six patients hospitalized for first-episode DSM-IV schizophrenic disorder participated in the study. In addition to 6 weeks of treatment with olanzapine, 10 mg/day, patients were randomly allocated in a double-blind design to receive either reboxetine, 4 mg/day, (N=13) or placebo (N=13). Results: Ten patients in each group completed the 6-week trial. Patients given olanzapine and reboxetine demonstrated a significantly lower increase in body weight (mean=2.5 kg, SD=2.7) than those given olanzapine and placebo (mean=5.5 kg, SD=3.1). Significantly fewer patients in the olanzapine/reboxetine group (N=2 of 10) than in the olanzapine/placebo group (N=7 of 10) gained at least 7% of their initial weight, the cutoff for clinically significant weight gain. The addition of reboxetine to olanzapine treatment was safe and well tolerated by the patients. A between-group difference in the reduction of Hamilton depression scale scores was seen that favored the olanzapine/reboxetine group (mean difference=-3.1, SD=1.25). Conclusions: The selective norepinephrine reuptake inhibitor reboxetine may reduce olanzapine-incluced weight gain in schizophrenia patients, and activation of the adrenergic system may attenuate weight gain induced by atypical antipsychotic agents.