Comparison of serotonin agonists in combination with phentermine for treatment of obesity

Treatment with a combination of serotonin and adrenergic agonists produces weight loss in obesity. Fluoxetine (FL), but not fenfluramine (FEi, is beneficial for depression, and many patients cannot be taken off FL. This study compared the effectiveness of FL (20-60 mg/d, N = 42) vs FE (10-60 mg/d, N = 26) when combined with phentermine (PH: 8-37.5 mg/d) in 68 patients treated for an average of 20 wk. All patients received PH and instruction in diet, exercise, and behavior modification. Baseline weight (wt) was 120.6±34.3 kg for FE and 127.6±30.1 kg for FL. The FE group lost 12.2% of initial wt (14.3 kg) vs 8.9% (11.0 kg) for the FL group (p<.02). There were no significant differences between groups in blood pressure (BP), serum cholesterol, triglycerides, or glucose at baseline. FE produced significant decreases in systolic BP (132 to 124 mm Hg, p<.02), serum cholesterol (205 to 173 mg/dl, p<.00), and serum triglycerides (150 to 112mg/dl, p<.00). FL produced a significant decrease only in systolic BP (134 to 125 mm Hg, p<.03). The decreases in glucose were not significant in either group. Adverse events were modest and there were no differences between groups. We conclude that in combination with PH, both fluoxetine and fenfluramine produce wt loss and improvement in complications of obesity, but fenfluramine is more effective.