Search

The diet pills fenfluramine and dexfenfluramine appear to increase the risk of heart valve insufficiency. This condition occurs when the valves do not close properly. Researchers analyzed the rate of heart valve insufficiency over a five-year period in approximately 20,000 obese people, half of whom were taking one of these two drugs or another diet pill called phentermine. Within five years, there were 11 cases of heart valve insufficiency in the people taking diet pills, but none in those who were not. The aortic valve was most often affected.

The diet pill dexfenfluramine appears to increase the risk of heart valve insufficiency. This condition occurs when the valves do not close properly. Researchers analyzed the rate of heart valve insufficiency in 1,072 overweight people, about 700 of whom were taking dexfenfluramine and 354 were taking a placebo. The rate of aortic valve insufficiency, mitral valve insufficiency or both was 7% in the group taking dexfenfluramine and 4.5% in those taking a placebo. The aortic valve was most often affected and most patients had mild insufficiency. However, the average duration of treatment was only 72 days.

The diet pills fenfluramine, dexfenfluramine and/or phentermine may increase the risk of heart valve insufficiency. This occurs when the valves do not close properly. Researchers analyzed the rate of heart valve insufficiency in 233 obese patients who had taken one or a combination of these pills and in 233 people who had not. Compared to those who did not take the pills, the risk of heart valve insufficiency was 12 times higher in obese people who took dexfenfluramine, 24 times higher in those who took dexfenfluramine and phentermine and 26 times higher in those who took fenfluramine and phentermine.

Animal studies show that fenfluramine and its derivative dexfenfluramine both cause damage to nerve cells in the brain that produce serotonin. It is not known whether this occurs in humans. These appetite suppressants go by the trade names Pondimin and Redux, respectively. A review of the animal studies found that the doses that cause damage in animals are the same doses used in humans to treat obesity. These drugs also increase the risk of pulmonary hypertension, especially when used for more than 3 months., Objectives. -- Obesity is an important clinical problem, and the use of dexfenfluramine hydrochloride for weight reduction has been widely publicized since its approval by the Food and Drug Administration. However, animal and human studies have demonstrated toxic effects of fenfluramines that clinicians should be aware of when considering prescribing the drugs. Our purpose was to systematically review data on brain serotonin neurotoxicity in animals treated with fenfluramines and the evidence linking fenfluramines to primary pulmonary hypertension (PPH). Data Sources. -- Archival articles and reviews identified through a computerized search of MEDLINE from 1966 to April 1997 using "fenfluramine(s)," "serotonin," "neurotoxicity," "behavior," "anorexigens," "weight loss," and "primary pulmonary hypertension" as index terms. Study Selection. -- Reports dealing with long-term effects of fenfluramines on brain serotonin neurons, body weight, and pulmonary function in animals and humans. Data Extraction. -- Reports were reviewed by individuals with expertise in serotonin neurobiology, neurotoxicity, neuropsychiatry, and pulmonary medicine and evaluated for appropriateness for inclusion in this review. Data Synthesis. -- Fenfluramines cause dose-related, long-lasting reductions in serotonin axonal markers in all the animal species tested and with all the routes of drug administration used. Doses of fenfluramines that produce signs of brain serotonin neurotoxicity in animals are on the same order as those used to treat humans for weight loss when one takes into account known relations between body mass and drug clearance. However, no human studies have been conducted, and the pathological and clinical potential for neurotoxicity in humans is unknown. Appetite suppressants -- most commonly fenfluramines -- increase the risk of developing PPH (odds ratio, 6.3), particularly when used for more than 3 months (odds ratio, [is greater than] 20). Conclusions. -- Fenfluramine and dexfenfluramine have been demonstrated to damage brain serotonin neurons in animal studies. It is not known if such damage occurs in humans or if there are clinical consequences. Use of fenfluramines is associated with an increased risk of PPH. Future studies should address the long-term consequences of prolonged use of fenfluramines. JAMA.1997;278:666-672

Long-term use of diet pills containing fenfluramine or its derivatives may increase the risk of pulmonary hypertension. This lung disease is characterized by high blood pressure in the blood vessels of the lungs. Researchers compared the use of fenfluramine and its derivatives by 95 people with pulmonary hypertension and 355 healthy volunteers. Use of fenfluramine and its derivatives led to a six-fold increased risk of pulmonary hypertension. Those who took the drugs for more than three months had 23 times the risk.

The US Department of Health and Human Services (DHHS) recommends medical screening of people who have used the popular appetite suppressants fenfluramine and dexfenfluramine. FDA has received reports of at least 113 cases of heart valve disease thought to be related to the diet pills, and the drugs were withdrawn on September 15, 1997. DHHS advises physicians to examine every patient exposed to the drugs. An echocardiogram is recommended for patients with signs or symptoms of valvular disease, and in any patient before invasive procedures.

Heart valve damage from the diet pills dexfenfluramine and phentermine/fenfluramine will not get worse and may even recover once the drugs are stopped. This was the conclusion of a study of 1,142 obese patients who had stopped taking the drugs and had an echocardiogram between one and two years later.

Most people who took the diet pills fenfluramine or dexfenfluramine will probably not develop serious heart valve disease. These drugs were withdrawn by the manufacturer in 1997 after the FDA reported an increased risk of heart valve disease in people who took the drugs. A study published in 2000 confirmed this risk, but found that most cases of heart valve disease were mild. Other studies have shown that the heart valves may return to normal when the drugs are discontinued. People who took high doses of the drug for more than three months have the highest risk of valve disease.

The diet drugs fenfluramine and dexfenfluramine appear to increase the risk of aortic regurgitation but not mitral valve regurgitation or any other heart disease. Aortic and mitral valve regurgitation occur when blood flows backward through the valve. It is a form of heart valve disease. Researches compared the rate of heart valve disease in 1,473 patients, 479 of whom had taken dexfenfluramine and 455 of whom had taken fenfluramine/phentermine. Compared to people who had never taken the diet pills, those who had taken dexfenfluramine had twice the risk of aortic regurgitation and those who had taken fenfluramine/phentermine had three times the risk.

People who have taken the diet pills fenfluramine or dexfenfluramine should have regular medical examinations to detect heart valve disease. These drugs first appeared in the 1990s, and seemed to be effective in the treatment of obesity. But in July, 1997, a paper was published reporting heart valve disease in 24 patients who had taken the drugs. The FDA subsequently ordered the drugs to be withdrawn from the market. Three 1998 studies confirm the link between these drugs and heart valve disease. However, the risk was low in patients who took the drugs for short periods of time.

The appetite suppressants fenfluramine, dexfenfluramine and phentermine should only be used in patients with severe obesity. Several reports in the 1990's have linked these diet pills to pulmonary hypertension even when the drugs were used for one month or less. This same phenomenon occurred between 1967 and 1972 and was linked to the appetite suppressant aminorex. In 1997, a study revealed that 24 women developed heart valve disease after using fenfluramine and phentermine, a combination commonly called fen-phen. These drugs should not be used for cosmetic weight loss.

The benefits of fenfluramine and its derivatives probably outweigh their side effects. One side effect recently discovered was pulmonary hypertension, a condition characterized by high blood pressure in the lungs. Researchers found that almost one-third of 95 people with pulmonary hypertension had been taking fenfluramine. This translates to a risk 23 times greater than in people who don't use the diet pill. However, obesity has serious health consequences and drug therapy would save an estimated 280 lives for every 1 million persons treated. Fenfluramine would cause an estimated 14 deaths for every 1 million persons treated.