Appetite suppressants: the big hope, the big letdown

If only we could just not want to eat. Wouldn’t that make staying healthy so much easier? We’d eat what we needed because it was the right thing to do for our health, like brushing our teeth, not because it was such a rewarding source of pleasure.

No such luck. We love food. We’re hard-wired to want it. That’s part of what assures survival of the species, and we further cultivate our appetites for it by associating food with every other kind of satisfying joy from birth onward — maternal comfort, familial stability, social interaction, celebration, etc.

But enjoying food for more than physical sustenance is part of the reason we have an obesity crisis.

So appetite suppressants are the most widely used of the medicines and supplements used for weight-loss therapy. The logic is simple: if you have no appetite, you’ll eat less and you’ll lose weight.

Having no appetite could be a powerful defense against the world of “eat more, eat now” messages that constantly bombard Americans, stimulating our appetites by any means available.

A person who is suddenly finding it easier to pass on the junk and the massive servings can exercise a lot more control over the quantity and quality of their intake. And that’s just the boost some people need to make a routine of healthy dietary changes, and that boost can sometimes come from a medication.

But it’s no get-out-of-weight-free card. Chemically, appetite suppressants act on the central nervous system (CNS) to decrease appetite or cause the feeling of fullness that doctors call satiety. But appetite suppressants are also the most controversial because of potentially dangerous side effects.

Some appetite suppressants are addictive, and their effect tends to wear off if used over an extended time, such that people need to take larger doses to produce the same result, which in turn increases the risk of addiction, which in turn increases other risks.

Among prescription appetite suppressants, most people remember the Fen-Phen debacle. The combinations of phentermine and fenfluramine or dexfenfluramine were prescribed for thousands of people with weight problems in the mid-1990s.

Fen-Phen was hailed as the new magic bullet, and there was tremendous excitement about it, as early trials showed promising results. People also had a sense of confidence about its safety and efficacy, because it had been through the rigors of FDA testing.

Phentermine is an andrenergic, which means it is activated by the body’s natural epinephrine (adrenaline) supply or another epinephrine-like substance. Like an amphetamine, it acts to stimulate metabolism and suppress the appetite.

Fenfluramine and dexfenfluramine also increased serotonin levels in the brain and enhanced the appetite suppression effects of phentermine while alleviating some of its unpleasant stimulant effects.

Fen-Phen was indeed effective in helping people lose weight, but it also turned out to be associated with numerous cases of valvular heart damage. Some people died, others were hospitalized. Even though the combination drug was subjected to extensive testing, this was a side effect that researchers hadn’t discovered before it was released to the public and subject to broader use.

In 1997, fenfluramine and dexfenfluramine were withdrawn from the US market to much objection and outcry from patients — presumably those without heart damage — who were successfully losing weight with the help of Fen-Phen. Only phentermine remains available.

The Fen-Phen situation remains an oft-cited example of the very real danger of drug interactions. Even with the rigorous testing the drug was subjected to in controlled studies, the problem with heart trouble wasn’t detected until it was released and began to be used by thousands of patients. Only then did the frequency of heart problems become clear.

Another weight-loss medication that was pulled is Phenylpropanolamine. Once sold under prescription as Destrim, and over the counter in various weight-loss products and cold treatments, it was removed from the market in 2000 after a large study found that it increased the risk of hemorraghic stroke.

Sibutramine (Meridia) was approved for weight-loss treatment in 1998, just in time to fill the void left by Fen-Phen. Not surprisingly, an eager public seized upon it as the new hope.

Like fenfluramine and dexfenfluramine, sibutramine affects the function of serotonin in the brain, though sibutramine goes about it differently, and it doesn’t produce the adverse side effects on the heart. Sibutramine at 10 to 30 mg per day has helped patients reduce their weight by up to 10 percent over six to 12 months, which is above average. In three studies, up to 25 percent of lost weight was regained within one to six weeks of stopping medication, and in another study, up to 80 percent of weight lost was regained within three months of stopping medication.

But patients who stay on sibutramine typically gain back less than 20 percent of the weight lost.

And there’s the rub! Unlike most weight-loss medications, sibutramine actually is approved by the FDA for long-term use of more than 12 months, so patients may be able to get a supportive regimen of medication for a longer period with sibutramine.

But once again, there’s no perfect safe solution. Other safety concerns about sibutramine led to its removal from the market in Italy, and France and Great Britain are considering similar action because of reports of heart attack, stroke, arrhythmia and some deaths in patients taking sibutramine, even though a clear causal relationship hasn’t been established.

Doctors and researchers know that sibutramine does increase blood pressure and heart rate, but no one knows yet if it’s responsible for causing heart attack or some other serious adverse effects. Until this is better understood, if your doctor suggests using sibutramine, remember that diligent tracking of your blood pressure will be essential.

And if you already have coronary artery disease, heart failure or high blood pressure, remember that the purpose of losing weight is to improve your health. The amount of loss you could get from sibutramine would not justify recklessly elevating your current risks, so you probably should not be on sibutramine at all.