Objectives: Patients with bipolar disorder (BD) have an increased risk of obesity as well as psychotropic-associated weight gain. The objective of this study was to compare sibutramine and topiramate as adjunctive treatments for psychotropic-associated weight gain in overweight or obese outpatients with BD. Methods: In this 24-week, open-label, flexible-dose, comparison trial, 46 outpatients with bipolar disorders who had a body mass index (BMI) ≥30 kg/m2, or ≥27 kg/m2 with obesity-related comorbidities, and psychotropic-associated weight gain were randomly assigned to receive sibutramine (n=18; 5-15 mg/day) or topiramate (n=28; 25-600 mg/day). The primary outcome measure was weight loss. Secondary measures included changes in BMI, percent body weight loss, and mood symptoms. Results: Patients randomized either to sibutramine or topiramate lost comparable amounts of weight (4.1±5.7 and 2.8±3.5 kg, respectively) and displayed similar rates of weight loss (0.85 and 0.82 kg/week, respectively). However, only four (22%) patients receiving sibutramine and six (21%) patients receiving topiramate completed the 24-week trial. In addition, the attrition patterns for the two drugs were different, with patients discontinuing topiramate doing so early in treatment and patients discontinuing sibutramine doing so throughout treatment. Also, higher ratings of manic and depressive symptoms significantly increased risk for early topiramate discontinuation compared to that for sibutramine. Conclusions: Adjunctive sibutramine and topiramate may have comparable weight loss effects in overweight or obese bipolar patients with psychotropic-associated weight gain, but are each associated with similarly high discontinuation rates. In addition, they may have different attrition profiles. Compared to sibutramine, discontinuation of topiramate may be more likely to occur early in treatment and may be more dependent upon manic and depressive symptoms. © 2007 Blackwell Munksgaard.