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Tracking the 'Fen-Phen' Drug Trend


Caution: see Mayo Clinic study about the association between fen-phen and valvular heart disease and the US Food and Drug Administration Health Advisory on Fenfluramine-Phentermine for Obesity .

Obesity is the most common chronic disease in this country—an estimated 57 million Americans are seriously overweight or obese. Increasingly, physicians are using pharmacologic tools to help patients battle obesity. However, weight loss medications are not right for everyone.

Fenfluramine and phentermine (fen-phen), the now-popular prescription combination of appetite suppressants, can help reduce weight and diminish food cravings when combined with regular exercise and a low-fat diet. The two medications promote weight loss by acting on the adrenergic and serotonergic receptors in the brain. Fenfluramine increases the activity of serotonin, which suppresses appetite and makes the patient feel full. Phentermine is thought to speed up the body's calorie-burning mechanisms. Neither drug is an amphetamine, nor are they addictive.

According to Steven Lamm, MD, a Manhattan internist who has written a book on the fen-phen protocol (1) based on his experience treating hundreds of patients with the medications, the drugs can produce a 10% to 20% loss of body weight, most of it occurring in the first 6 months. He says the average patient loses 6 to 12 lb the first month and 3 to 5 lb a month thereafter.

"Just like hypertension, asthma, and diabetes, obesity is a chronic, incurable medical condition that affects millions of Americans, active athletes included," notes Lamm. "For some, cutting calories and exercising more isn't always enough to overcome a genetic propensity for obesity.

Fenfluramine and phentermine, though available for more than 20 years, have been prescribed separately, used infrequently, and only for 12 weeks, as their labels directed. In 1992, pharmacologist Michael Weintraub, MD, of the University of Rochester School of Medicine and Dentistry in Rochester, New York, was the first to combine fenfluramine and phentermine and put the medications to a long-term test. The results of his 4 year study (2-8) of 121 patients demonstrated that when the drugs were used in combination, along with a supervised exercise program, study participants lost an average of 16% of their weight in 8 months, an average loss of 30 lb. Those on placebo lost only 10 lb, or 5% of body weight. The study found no problems with addiction to the drugs or serious side effects. Among the common side effects were insomnia, irritability, agitation, nervousness, and anxiety; most disappeared after a short while.

Buoyed by Weintraub's reports and the publication of Lamm's book, prescriptions for the two drugs rose from about 60,000 in 1992 to more than 1 million for each in 1996. The medications cost about $70 per month and are not usually covered by the patient's health insurance.

Susan J. Speer, MS, RD, instructor of clinical nutrition at the University of California Los Angeles/Santa Monica Family Practice Residency in Santa Monica, says she believes a change of thinking in the medical community about obesity has influenced diet-drug prescribing patterns. "From research, it's becoming more apparent that obesity is a genetic problem, and not a problem of character," she says.

Deciding if the fen-phen protocol is right for a patient requires a delicate balancing act, Speer says. The use of appetite suppressant medication may be associated with an increased risk of primary pulmonary hypertension, Speer says. "Though primary pulmonary hypertension is very rare, that's the side effect that gives me the greatest pause," she says. In addition, most appetite suppressant drugs are approved for only 3 months of treatment, in which the drugs typically produce a 10% to 15% loss of body weight (20 to 30 lb), she says. "That's not a great loss for some, but it's enough to improve glucose tolerance, improve the lipid profile, and decrease blood pressure," Speer says. However, when patients stop taking the drugs, most of the weight returns. "Intermittent use may improve long-term weight maintenance, but we don't have much experience with that yet," she says.

"We know that the short course of these drugs is as ineffective as other methods (diet and exercise), and there is the rare side effect of primary pulmonary hypertension," Speer says. "Though more exercise and better diet are also not effective, at least their side effects confer some of the same benefits as weight loss: energy, self esteem, improved lipid profiles, improved glucose tolerance, and decreased blood pressure."

Elizabeth Joy, MD, a family practice physician in Salt Lake City, says the medications are not designed for patients who want to drop a quick 10 lb. Joy attended a seminar on the drugs, their side effects, and how to safely prescribe them. "These drugs are for patients who have failed repeatedly at dieting or are at risk of heart disease, stroke, diabetes, and early death."

Because all medications can have side effects, Lamm says that these anorectic medications should be reserved for two groups: obese people who weigh at least 20% more than their ideal body weight or have a body mass index of 28 or more (occasionally lower if they have comorbid conditions such as hypertension, diabetes, or hyperlipidemia) and severely overweight people who already are experiencing serious health complications from their weight, such as high blood pressure and diabetes.

It seems paradoxical that though athletes exercise daily, some have problems with their weight. "Weight is an eternal problem for these people, and they need special help," says Charles L. Brown, Jr, MD, an internist and medical consultant to the New Orleans Saints professional football team. "For those football players who continue to struggle with their weight, even after exercising for 40 nonstop minutes three to four times a week and limiting their caloric intake, we will use fenfluramine and phentermine to jump-start their weight loss," he says. "There is no question in my mind that the pills work. I use the medication carefully and judiciously, and with great documentation."

For obese athletes, Brown favors reserving appetite-suppressing medication for when all else has failed. "The big mistake would be to let athletes know there are prescription medications that are going to solve their weight problems and then have them forget about the regular exercise and caloric restriction," he says.

A similar drug, dexfenfluramine, was approved by the US Food and Drug Administration in April for the treatment of obesity. Lamm says the new drug, released in August, will not automatically replace fenfluramine, nor supplant the fen-phen protocol. "Tolerance to various drugs differs," he says. "Just as every heart patient doesn't have a positive response to diuretics or to calcium blockers, we can't expect every obesity patient to be successful on dexfenfluramine. Some people will continue to do better on the old drugs."


  1. Lamm S, Couzens GS: Thinner at Last: The New Medicine That Releases Your Brain's Power to Bring About Permanent Weight Loss. New York City, Simon & Schuster, 1995
  2. Weintraub M, Sundaresan PR, Madan M, et al: Long-term weight control study: I (weeks 0 to 34): the enhancement of behavior modification, caloric restriction, and exercise by fenfluramine plus phentermine versus placebo. Clin Pharmacol Ther 1992; 51(5):586-594
  3. Weintraub M, Sundaresan PR, Schuster B, et al: Long-term weight control study: II (weeks 34 to 104): an open-label study of continuous fenfluramine plus phentermine versus targeted intermittent medication as adjuncts to behavior modification, caloric restriction, and exercise. Clin Pharmacol Ther 1992;51(5):595-601
  4. Weintraub M, Sundaresan PR, Schuster B, et al: Long-term weight control study: III (weeks 104 to 156): an open-label study of dose adjustment of fenfluramine and phentermine. Clin Pharmacol Ther 1992;51(5):602-607
  5. Weintraub M, Sundaresan PR, Schuster B, et al: Long-term weight control study: IV (weeks 156 to 190): the second double-blind phase. Clin Pharmacol Ther 1992;51(5):608-614
  6. Weintraub, Sundaresan PR, Schuster B, et al: Long-term weight control study: V (weeks 190 to 210): follow-up of participants after cessation of medication. Clin Pharmacol Ther 1992;51(5):615-618
  7. Weintraub M, Sundaresan PR, Cox C: Long-term weight control study: VI: individual participant response patterns. Clin Pharmacol Ther 1992;51(5):619-633
  8. Weintraub M: Long-term weight control study: conclusions. Clin Pharmacol Ther 1992;51(5):642-646