A close look at fenfluramine and dexfenfluramine.

In an effort to combat obesity, several medications have been developed. The nonamphetamine anorectics, such as phentermine, fenfluramine, and dexfenfluramine, have been recommended as first-line drug therapy for the treatment of obesity once diet and exercise alone have failed. Numerous studies have shown that these agents can promote weight loss when combined with diet restriction and exercise. Although fenfluramine and dexfenfluramine lack the abuse potential of amphetamine and its congeners, these agents are associated with drug interactions and adverse effects. Concomitant administration of fenfluramine or dexfenfluramine with medications that enhance serotonin levels (e.g., antidepressants, monoamine oxidase inhibitors, and migraine medications) can precipitate serotonin syndrome. Sudden discontinuation of fenfluramine or dexfenfluramine after prolonged administration can precipitate withdrawal depressive symptoms. Primary pulmonary hypertension, a potentially fatal disorder, has been reported to occur approximately 30 times more frequently in patients receiving anorectic agents for more than 3 months compared to the general population. More recently, the association of these popular anorectics with valvular heart disease has caused increased concerns about their use. The risks of primary pulmonary hypertension, valvular heart disease, and the occurrence of convulsions, coma, and death in overdose appear to be equally likely with dexfenfluramine and fenfluramine. In addition, many patients who lose weight while taking these anorectics rapidly regain it after the medication has been discontinued.