Diet Drug Disaster: The Story of Redux and Fen-Phen*

The Fen-Phen Diet combines two FDA approved drugs. Although both drugs showed significant weight loss in controlled studies, no long-term studies of safety had been performed at the time of approval. It was thought that fenfluramine and dexfenfluramine, the active racemate of fenfluramine, suppressed appetite like other amphetamine-related drugs. Phentermine was thought to act as a balance to the adverse effects of abstinence from food and irritability from CNS stimulation caused by dexfenfluramine. Primary pulmonary hypertension (PPH) was known to be a rare risk at time of approval and prompted the recommendation that use be restricted to morbidly obese patients for short periods of time (6–8 weeks). An unanticipated danger of using these two drugs in combination is that together they can produce an overdosage of serotonin. The development of cardiac valvulopathies in otherwise healthy people recalled similar pathology in response to overdosage of serotonin from other medications or from a serotonin producing tumor of the Gl (carcinoid syndrome). Serotonin pharmacology is considered to illustrate the complexity of this remarkable chemical that has properties of neurotransmitter and hormone. Since this anorexogenic epidemic affected millions of patients and because there are potential permanent residual pathologies, pharmacists will continue to be queried about the topic. A review of the Redux/Fen-Phen history, pharmacology of the anorexigenics, and interactions with serotonin agonists and antagonists is presented to provide the pharmacist with a succinct and current account of this dark chapter in pharmacotherapy.