Dexfenfluramine stimulates serotoninergic activity by inhibiting
serotonin reuptake into presynaptic neurons and by enhancing its release into brain synapses. Based on the
serotonin hypothesis of appetite control these effects would be expected to reduce food intake and thus
body-weight. Studies in animal models and severely
overweight patients have confirmed the effectiveness of
dexfenfluramine as a weight-
reducing agent which appears to be well tolerated. Permanent
weight loss is the goal of weight-reducing strategies and, based on current clinical evidence,
dexfenfluramine appears to exert a weight reducing effect over periods of up to 12 months without development of tolerance, a problem that has limited the long term use of other pharmacological agents used in the treatment of this disorder.
Dexfenfluramine facilitated
weight loss in patients who had not responded satisfactorily to other weight-reducing strategies, prevented relapse in those patients who had achieved
weight reduction by other methods, and corrected disturbed eating patterns (and therefore reduced
weight gain) in small studies involving patients with
premenstrual syndrome,
seasonal affective disorder and
nicotine withdrawal syndrome. Follow-up of the longest study reported with
dexfenfluramine suggests that continued
therapy is required in severely
overweight patients if
weight loss is to be maintained.
Dexfenfluramine has not been directly compared with nonpharmacological measures of weight control such as behaviour modification or exercise programmes. The decision that pharmacological means are indicated in
overweight patients must be highly individualised, and must consider the many complex factors that often contribute to
overweight states, as well as the anticipated magnitude of
drug effect. Despite such a cautionary note, and the expected need (at this stage of its development) for an expanded clinical study programme in certain areas,
dexfenfluramine is a clear advance in the pharmacological approach to improved management of
overweight individuals.