Appetite Suppressants and Pulmonary Hypertension
Reprinted from Eating Disorders Review
May/June 2000 Volume 11, Number 3
©2000 Gürze Books
The fenfluramines may be off the market, but they are back in the news. This time they have been linked to development of primary pulmonary hypertension, or PPH.
Dr. Stuart Rich and colleagues have reported an increased outbreak of cases of pulmonary hypertension traced to use of appetite suppressants, particularly to the combination of fenfluramine and phentermine ("fen-phen"). The trend was reported from the Surveillance of North American Pulmonary Hypertension (SNAP) study, which included cases from 12 large hospital centers in the U.S. and Canada (Chest 2000;117:870).
Dr. Rich and a group of pulmonary hypertension specialists organized SNAP to track cases of PPH linked to commonly used medications, especially appetite suppressants and chemically related substances. Eventually 579 patients were enrolled in the SNAP study, including 205 with PPH and 374 with pulmonary hypertension from other causes (secondary pulmonary hypertension). The study was conducted between September 1996 and December 1997, a time when diet pill use was markedly increasing in the U.S.
Fenfluramines had the strongest association with PPH
Use of appetite suppressants was common in both groups but of all medications surveyed, only the fenfluramines showed a significant preferential association with PPH compared to SPH. The association was stronger with longer use and more pronounced in recent users than in those who had used the agents some time ago. PPH has been reported in fen-phen users after as little as 23 days. A high number—11.4%ó of patients with SPH had used appetite suppressants.
A pattern first seen in Europe
PPH is a relatively rare disease, but an epidemic of PPH occurred in the 1960s in Switzerland, Austria, and Germany in association with the use of the appetite suppressant aminorex fumarate. Later, the International Primary Pulmonary Hypertension Study discovered a strong association between PPH and the use of appetite suppressants, particularly the fenfluramine derivatives (N Engl J Med 1997; 335:602).
After the FDA approved dexfenfluramine for extended use as an appetite suppressant in the U.S., and with the growing use of "fen-phen," an unusually high number of cases of PPH began appearing. After the outbreak in Europe, use of appetite suppressants was limited to 3 months. In the U.S., however, there was no limit on duration of use. In response to concerns about other adverse effects, fenfluramine appetite suppressants were withdrawn from the market in September 1997.