Fenfluramine was marketed by American Home Products (later known as Wyeth) as Pondimin, but was shown to cause potentially fatal pulmonary hypertension and heart valve problems, which eventually led to its withdrawal in 1997 and legal damages of over $13 billion.

[1] The New York Psychiatric Institute, associated with Columbia University, the Research Foundation of the City University of New York, and Mount Sinai Medical Center tested fenfluramine intravenously on more than 100 Black and Hispanic boys between the ages of 6 and 10, with delinquent older brothers, to test the theory that delinquent behavior could be predicted by serotonin levels.

[5] An article in Nature reports that these tests were published as a study in Archives of General Psychiatry in 1997 and that "The New York trial, funded largely by the Lowenstein Foundation, with some support from the National Institute of Mental Health, was halted in 1995, two years before the drug was withdrawn.

"[1] In 1994, Wyeth official Fred Wilson expressed concerns about fenfluramine's labeling containing only four cases of pulmonary hypertension when a total of 41 had been observed, but no action was taken until 1996.

However, the medical officer of the Food and Drug Administration (FDA), Leo Lutwak, insisted upon a black box warning of pulmonary hypertension risks.

The FDA subsequently received over a hundred additional reports of valvular heart disease in people taking fen-phen, fenfluramine alone, or dexfenfluramine alone.

After reports of valvular heart disease and pulmonary hypertension, primarily in women who had been undergoing treatment with fen-phen or (dex)fenfluramine, the FDA requested its withdrawal from the market in September 1997.

[10][12] The action was based on findings from doctors who had evaluated people taking these two drugs with echocardiograms, a procedure that can test the functioning of heart valves.

The authors felt that combining fenfluramine and phentermine capitalized on their pharmacodynamic differences, resulting in equivalent weight loss, fewer adverse effects, and better appetite control.

[21] Intramural National Institutes of Health (NIH) double-blind protocols to demonstrate the efficacy of fen-phen in alcohol and cocaine addiction were designed,[22] but never performed.

The findings on fen-phen, specifically fenfluramine, causing valvular heart disease and pulmonary hypertension prompted a renewed interest in the deleterious effects of systemic serotonin.