Weight Loss Medications: More Lost Than Gained

Psychiatrists are often asked to treat weight gain associated with depression, psychotropic drugs, or binge eating. But recent reports of medical complications with fenfluramine-phentermine (fen-phen) combinations and the subsequent removal of fen-phen from the market at the suggestion of the FDA, force us to look closer at these medications. Sympathomimetic compounds such as phentermine, phenmetrazine, diethylpropion, and phenylpronalolamine increase beta-adrenergic activity or reduce alpha-adrenergic activity to promote weight loss, but these medications cause tolerance and are dangerous to patients with cardiovascular disease.1 Medications with serotonin (5HT) reuptake inhibiting, releasing, and agonist properties such as fenfluramine and dexfenfluramine directly reduce appetite and eating behaviors. These medications have been very popular; however, a randomized study of 822 patients (mean weight, 97 kg) found that dexfenfluramine led to a mean weight loss of only 9.8 kg versus 7.2 kg with placebo, although twice as many dexfenfluramine patients lost at least 10 kg.2 Another study showed that fen-phen produced an average weight loss of 9.4 kg over three years versus no sustained weight loss in controls.1 SSRIs like fluoxetine can produce weight loss in some patients, but significant gains in others. Frequently, a serotonergic compound like …