In my last article, I discussed the development of the diet pill phenomenon. This brilliant marketing strategy changed the course of the medical treatment for obesity by grouping together different kinds of drugs that might (or might not, for that matter) have some relation to weight loss, and then selling the patient all the drugs at once. The plan was enormously lucrative for the drug companies who manufactured the chemicals, and also for the so-called “fat doctors” who prescribed them. But before we put all the blame on the drug companies and the doctors, we must face a certain reality. The public was very willing to hear the message that overweight can be treated with chemicals.
Amphetamines were found to help weight loss early in the studies of drug-related obesity treatment. They cause weight loss by suppressing the appetite, but they fell from favor because of the potential for drug abuse. In fact, the prescribing of amphetamines for weight loss has been severely restricted by medical and pharmacy laws in many states.
The dampened enthusiasm for drug therapy following the big Diet Pill heyday of the 1960s and early 1970s resulted in a hiatus of some 20 years following 1973. What was “needed” were drugs that resembled amphetamines in their action, but which didn’t have the associated drug abuse problems. In the mid-1990s, enthusiasm was rekindled.
The Development Of “Safer” Alternatives
The unwanted extreme central nervous system excitation caused by the amphetamines led to the development of drugs known as noradrenergic (nor-ad-dren-ER-jik) agents, which depressed appetite, but didn’t cause addiction. Noradrenergic agents, also known as norepinephrine-like agents (nor-epi-NEF-er-in) also promote weight loss primarily by suppressing appetite. These newer drugs were called by jawbreaking names such as phenteramine, phendimetrazine, phenmetrazine, diethylpropion, benzphetamine, mazindol, and phenylpropanolamine (which was available over-the-counter, without a prescription).
Also being developed at the same time, were a group of drugs known as serotoninergic (sero-tone-in-NER-jik) agents, which acted on serotonin, a chemical important to brain function. Researchers wanted these new drugs because it had been discovered that elevated levels of serotonin in the brain are associated with feelings of fullness, and with appetite suppression. The two most commonly prescribed drugs of this type were known as Pondimin and Redux (Fenfluramine and Dexfenfluramine).
Grouping Drugs – Again
In 1992, a panel of reseachers studying obesity in America gathered at a Washington D.C. conference sponsored by the National Institute of Health. The major issue of discussion was how it was that the more people were dieting and taking diet pills, the fatter the populace was becoming.
Meanwhile, at just about the same time as the NIH conference, a pharmacology research group at the University of Rochester (New York) was finishing up their study on the effects of a combination of two appetite suppressant drugs that seemed to be quite effective in promoting weight loss, especially when used together. These two drugs were fenfluramine (fen-FLUR-ah-mean) and phentermine (FEN-ter-mean).
Fenfluramine suppresses the appetite, but makes the patient drowsy. Phentermine counteracts the drowsiness because it is an amphetamine-like substance. Together, the drugs appeared to be more effective than either drug alone, and definitely more effective than low calorie diets with or without exercise. This drug combination was Fen/phen.
Fen/phen appeared on the market in 1993, and before long there were more than one million people taking it. Drug sales shot up to $100 million a year. “Fat Doctors” appeared again, but this time they called their offices Weight Loss Centers. The company called Nutri/Systems branched off into something referred to as Nutri/RX, and started distributing the drug combination in bulk.
The rationale for the combination in Fen/phen was that, by combining drugs that each had a different mechanisms of action, a lower dose of each drug could be used, thereby maintaining the efficacy while minimizing toxicity. Patients who took the combination reported fewer side effects than patients who took either drug alone. But even so, the benefits of the combination drug appeared less than would be desired. Researchers found that weight loss from Fen/phen tended to reach a plateau after about six months, and some weight regain usually occurred after two or three years, even when the patient continued taking the drug.
Fewer Side Effects Doesn’t Mean No Side Effects!
And side effects did raise their ugly heads. Patients reported drowsiness, diarrhea, and dry mouth. Some patients developed a group of symptoms referred to as the Serotonin Syndrome. These included confusion, disorientation, and loss of consciousness; muscle weakness, muscle tremors, and loss of muscle coordination; disturbed body heat maintenance (too cold or too hot); and frequent false positives when taking urine drug tests, screening for illegal drug usage.
The End Of The Rainbow
The Fen/phen phenomenon stopped suddenly in 1997 when it was withdrawn from the market. It was clearly causing heart valve problems, possible brain damage, and a very serious disease called pulmonary hypertension. Fen/phen was suspected as being the cause of at least 30 deaths!
Join me next time, when we’ll continue talking about the history of diets and dieting.