Attenuating effect of reboxetine on appetite and weight gain in olanzapine-treated schizophrenia patients: a double-blind placebo-controlled study

Rationale Search for safe and effective strategies to diminish weight gain associated with second generation antipsychotics (SGAs) is imperative. In the present study, we sought to replicate our preliminary findings, which indicated that coadministration of the selective norepinephrine reuptake inhibitor reboxetine attenuates olanzapineinduced weight gain. Materials and method Fifty-nine patients hospitalized for first-episode DSM-V schizophrenic disorder participated in this randomized double-blind study. Reboxetine (4 mg/day; 31 patients) or placebo (29 patients) was coadministered with olanzapine (10 mg/ day) for 6 weeks. Analysis was by intention-to-treat. Results Nine patients in each group prematurely discontinued the trial. Olanzapine/reboxetine-treated patients showed a significantly lower increase in body weight (mean=3.31 kg, SD=2.73) than their olanzapine/ placebo- treated counterparts (mean=4.91 kg, SD=2.45). Significantly fewer olanzapine/ reboxetine- treated patients gained at least 7% of their initial weight, the cutoff for clinically significant weight gain (6 [19.4%] of 31 patients vs 13 [46.4%] of 28 patients). Seven (22.6%) olanzapine/ reboxetine- treated patients compared to only one patient (3.6%) in the olanzapine/ placebo group revealed no weight change or even modest weight loss. Appetite increase was significantly lower in the olanzapine/ reboxetine than olanzapine/ placebo group and was correlated with attenuation of weight gain. Reboxetine addition was safe and well tolerated. Conclusions The results confirm that coadministration of reboxetine promotes a clinically meaningful attenuation of olanzapine-induced weight gain in schizophrenia patients. If substantiated in long-term studies, along with behavioral management and diet counseling, reboxetine may have a clinical utility in controlling SGA-induced weight gain.