Do you think the new drugs being sold to control hunger can finally help me to lose weight?
You are probably referring to so-called "Phen-Fen," two appetite suppressants that are indeed likely to help you to lose weight, when taken together. The bad news is that most people regain the lost weight after they stop taking the drugs. And there are some questions about their safety with long-term use.
"Phen" is an abbreviation for phentermine, while "Fen" stands for fenfluramine. The combination approach became popular when doctors recognized that smaller doses of both drugs taken together were more effective and produced fewer side effects than larger doses of either one taken alone.
Both phentermine and fenfluramine have long been available as prescription drugs -- phentermine under a long list of different trade names and fenfluramine as Podimin. Phentermine suppresses appetite by stimulating certain centers in the brain. The drug is usually well tolerated, but the more common side effects include nervousness, restlessness, difficulty sleeping, irritability and diarrhea.
The dose is 15 to 30 mg in the morning. Since the drug can elevate blood pressure or cause an irregular heartbeat, smaller doses are prescribed for those with hypertension or disturbances of heart rhythm.
Fenfluramine works by suppressing the uptake of serotonin in the brain. The usual dose of Pondimin is 20 mg three times a day just before meals. In April 1996 the Food and Drug Administration approved dexfenfluramine (Redux) "as an adjunct to a reduced-calorie diet, increase in exercise and other behavioral changes conducive to weight loss."
Dexfenfluramine is the active component (the D-form, hence the prefix "dex" in the name) of Pondimin, which is a mixture of D-and L-forms of the same chemical substance. As a result, the dose of dexfenfluramine is only half the dose (15 mg twice a day) of Pondimin since only the D-form of the latter is active in the body. Since both fenfluramine and dexfenfluramine act in a manner similar to a number of antidepressant drugs, such as Prozac or Zoloft, people using this type of antidepressant drug should not take these appetite suppressants or take a much smaller dose.
The most frequent side effects of fenfluramine and dexfenfluramine are usually mild and transient diarrhea, dry mouth and sleepiness. When used for more than three months in a row fenfluramine or dexfenfluramine is associated with a 23-fold increase in the development of the life-threatening disorder, primary pulmonary hypertension, which has a mortality rate of nearly 50 percent in four years. Early warning signs of primary pulmonary hypertension are new onset of shortness of breath with exertion, chest pain, fainting and swelling of the legs.
Fortunately, primary pulmonary hypertension is such a rare disease that even this great increase in risk translates into only 23 to 46 cases per million patients per year of exposure to these drugs. As a result of this potentially dangerous side effect, fenfluramine and dexfenfluramine should only be used by people who are at least 30 percent over desirable weight and have other risk factors for coronary heart disease (for example, high blood pressure, diabetes, or elevated blood lipids).
No studies have been carried out to show the safety and effectiveness of dexfenfluramine beyond one year, and studies with the Phen-Fen regimen found that the vast majority of patients return to their pretreatment weight once the drugs are stopped.
Dr. Margolis is professor of medicine and biological chemistry at the Johns Hopkins School of Medicine.
Pub Date: 9/17/96