An overview of the efficacy and safety of fenfluramine and mazindol in the treatment of obesity.

Abstract

To assess the validity of the perceptions that appetite-suppressant drugs are ineffective, potentially addictive, and fraught with side effects, we reviewed the effectiveness and safety of two such drugs with purported low abuse potential in the treatment of obesity: mazindol and fenfluramine hydrochloride. Relevant studies in English published before September 1991 were identified using MEDLINE, accompanied by a cross-referenced manual search. All randomized clinical trials conducted with adults for at least 6 weeks' duration with weight change as an outcome. Data extracted from each report included key study characteristics, clinical information, co-interventions, and outcomes, including dropouts due to either adverse drug effects or perceived lack of effect. Of 36 acceptable trials, 35 were double-blinded, 32 were placebo-controlled, and 13 were cross-over. Median duration of drug therapy was 12 weeks. In studies reporting such data, mean patient age was 41 years, and mean baseline weight was 84 kg (143% of ideal body weight). Among 1163 patients receiving drug therapy and 866 patients receiving placebo, mean weight loss across all trials was 5.2 and 1.9 kg, respectively (P < .001). Among 32 direct comparisons between drug and placebo, the mean weight loss by sample size was 3.0 kg greater in the treatment group (P < .001), and did not vary in subgroup analyses of trial type, drug, or dose. Similar proportions of treatment and placebo groups dropped out (20% vs 22%; P = .34); however, overall dropout rates were higher in parallel trials (25% vs 9% for crossover trials). Dropouts due to adverse drug effects were more common in the treatment group (7% vs 2%; P < .001), while those due to perceived lack of effect were more common in the placebo group (6% vs 2%; P < .001). Mazindol resulted in fewer dropouts due to adverse drug effects (4% vs 9%; P < .001) and a perceived lack of effect (1% v 3%; P = .04). No drug addiction or adverse drug effects requiring medical intervention were reported. The apparent short-term efficacy of these appetite-suppressant drugs and the lack of severe adverse drug effects or addiction suggest that they may be useful in the treatment of obesity. Further study of these agents with attention to long-term efficacy, safety, and health consequences is warranted.