Orlistat in clozapine- or olanzapine-treated patients with overweight or obesity:: A 16-week randomized, double-blind, placebo-controlled trial

Objective: Undesirable metabolic effects of modem antipsychotics, especially clozapine and olanzapine, merit development of new weight-control strategies, including pharmacologic ones. We investigated the feasibility of treatment with orlistat, a weight-control drug with no central effects, for overweight/obesity in clozapine- or olanzapine-treated male and female patients. Method: Add-on orlistat was prescribed for 16 weeks in a randomized, double-blind, placebo-controlled clinical trial to patients who were receiving stable clozapine or olanzapine medication and were aged 18 to 65 years, with no compliance with nonpharmacologic programs or hypocaloric diet required. The primary efficacy variable was body weight change. The study was conducted from 2004 through 2005. Results: Of 71 randomly assigned subjects, 63 were eligible for modified intent-to-treat analysis. While no statistically significant effect was observed in the whole population, male (but not female) patients benefited from treatment with orlistat (-2.36 kg vs. 0.62 kg on placebo, p =.0 11). There were 5 responders (16.1%) (those with >= 5% weight loss) that received orlistat versus 2 responders (6.3%) that received placebo (number needed to treat = 11), but the difference was not statistically significant. Conclusions: Without a hypocaloric diet, the effect of orlistat in overweight/obese clozapine-or olanzapine-treated patients is modest and may only be seen in men. More studies should define the optimal length of treatment and feasibility of combination of orlistat with behavioral programs in this population. Trial Registration: control led-trials. com/isrctn Identifier: ISRCTN65731856.