Fen-Phen Links: Research, Medical Reports, FDA Recommendations

Over the years, a variety of diets and drugs for the treatment of obesity have come and gone. More recently, newspapers, radio, and television have featured the rise and fall of the latest appetite-suppressants, dexfenfluramine and the combination of fenfluramine and phentermine (fen/phen). The rise occurred after approval of dexfenfluramine by the Food and Drug Administration (FDA); the fall was prompted by an unexpected outbreak of valvular heart disease related to the use of anorectic agents.

The fen-phen finale: a study of weight loss and valvular heart disease.

OBJECTIVE: To assess weight loss, as well as the prevalence of valvular heart disease, in 21 obese women who completed 2 years of treatment by fenfluramine and phentermine (fen-phen) in June 1997. RESEARCH METHODS AND PROCEDURES: Patients were 21 of 22 women who had completed a 1-year, open-label trial of fen-phen combined with lifestyle modification. This study describes the results of a second year of treatment. The presence of valvular heart disease, defined as aortic regurgitation of mild or greater severity and/or mitral regurgitation of moderate or greater severity, was assessed using two-dimensional, color Doppler and pulsed- and continuous-wave Doppler examinations. RESULTS: At 2 years, the 21 patients had a mean reduction in initial weight of 13.9 + 10.0%, which was significantly (p<0.001) smaller than their 1-year loss of 17.1 +/- 8.7%. Nine of 21 patients reported that they took fen-phen irregularly during the last 4 months of the study because of fears of developing health complications. These nine patients had a 2-year weight loss of 8.7 +/- 7.5%, compared with a significantly (p<0.04) larger loss of 17.6 +/- 10.5% for participants who reported taking medication regularly. Six of 20 (30%) patients met criteria for valvular heart disease. None of the six had signs or symptoms of this condition. DISCUSSION: Fenfluramine was withdrawn from the market on September 15, 1997 because of concerns that it was associated with valvular heart disease. The present findings are discussed in terms of the potentially favorable long-term benefits of combining lifestyle modification with weight loss medications that are both safe and effective.

Prescription weight loss pill use among Americans: patterns of pill use and lessons learned from the fen-phen market withdrawal

Background: Despite the popularity of antiobesity medications, there is a lack of population-based data on their use. In addition, response (termination of pill use and receipt of an echocardiogram) to the fenfluramine and dexfenfluramine market withdrawal among the public has not been described. Lessons learned from this event have implications for future withdrawals.

Methods: We used data from the Behavioral Risk Factor Surveillance System (BRFSS) a random-digit telephone survey. In 1998, six states included detailed questions about the use of prescription weight loss pills in the previous 2 years, n = 16,460 noninstitutionalized adults aged 18 years or older.

Effects of fenfluramine and phentermine (fen–phen) on dopamine and serotonin release in rat striatum: in vivo microdialysis study in conscious animals

We measured the effects of acute or chronic administration of fenfluramine and phentermine, alone or in combination, on brain dopamine and serotonin release into striatal dialysates of freely moving rats. Samples collected every 30 min were assayed in a single run by high-pressure liquid chromatography. Acute or chronic administration of fenfluramine (1 mg/kg, i.p.) did not significantly change dopamine concentrations in rat striatal dialysates, but increased those of serotonin by 182% (acute) and 124% (chronic). Phentermine (2 mg/kg, i.p.), on the other hand, significantly increased dopamine concentrations by 52% (acute) and 80% (chronic) without affecting those of serotonin. Administration of the drugs in combination (fenfluramine 1 mg/kg and phentermine 2 mg/kg) amplified the effects of each, increasing striatal dopamine concentrations by 209% (acute) and serotonin concentrations by 330% (acute) and 299% (chronic).