Our study aims at assessing the efficacy and safety of fluoxetine as compared with placebo in the treatment of obesity using a double-blind crossover design. We studied 42 obese women (body mass index 35.9 +/- 5.3 kg/m2). The obese patients were randomized to start treatment with fluoxetine (group A) or placebo (group B) for 3 months (period 1). After a 1-month washout period, treatment was crossed for the following 3 months (period 2). There was no significant difference in weight loss when the patients were treated with fluoxetine (group A period 1 and group B period 2) as compared with patients treated with placebo (group B period 1 and group A period 2). There were no significant differences in monthly weight reduction during both treatments. In conclusion, we demonstrated that serotoninergic drugs such as fluoxetine need further investigation before being used indiscriminately in obese subjects.