The Gravity of Weight

The daunting science of weight control.

Searching for Magic Bullets: Weight-Control Meds

Hope continues to spring eternal for magic elixirs that will lead to weight loss

There are no magic bullets for weight control
For those predisposed to excessive weight gain, weight control is a lifelong preoccupation. Any medication prescribed, therefore, will likely need to be continued indefinitely, analogous to those drugs used to treat chronic conditions like diabetes or hypertension.

Medications for weight control have had a particularly inauspicious past. Not only have there been extremely few medications available, particularly compared to those approved for other chronic medical conditions, but even these few have had remarkably short commercial half-lives.

Most recently, sibutramine (Meridia), approved for weight control, was withdrawn from the U.S. market by the Food and Drug Administration when reports of serious side effects appeared. Years ago, the combination fenfluramine and phentermine (fen-phen) was withdrawn when unexpected reports of deleterious cardiac valvular disease and deadly pulmonary hypertension developed in some patients over time. Furthermore, rimonabant (Accomplia), a medication that blocks cannabinoid receptors and decreases rather than increases hunger (i.e., the opposite of the marihuana “munchies”) was also withdrawn when scattered reports of depression and suicidal ideation occurred even in patients without a prior history of psychiatric illness.

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Dietary supplements, often sold in health food stores, have also been used, sometimes with dire consequences. The herbal compound Ephedra, for example, had been reported to lead to cardiac side effects, including myocardial infarctions, seizures, and even death. The major problem with these dietary supplements is that they are not FDA-controlled and hence not subject to any regulation. Several years ago, a New York Times expose, reported that many of the so-called diet pills sold under various names contained medications not listed among their ingredients and even medications for which one would need a prescription (e.g. diuretics, anti-epileptics, etc.) and that could lead to serious complications (e.g. dehydration, hypotension, etc.)

Furthermore, medication has been prescribed only for obesity (i.e., a body mass index--BMI greater or equal to 30 kg/m2 or 27 kg/m2 in those with serious medical morbidity related to excessive weight.) There has never been a medication developed or recommended for those who want to lose and keep off those proverbial 5 to 15 pounds, and medication is always prescribed in the context of the recommendation for lifestyle changes of regular exercise and dietary management (usually including lowering fat intake and caloric restriction.) 

Pills for weight loss with sensible diet and exercise

While there are many medications currently in development, two new medications have recently won FDA approval (at least for the time being): Belviq (lorcaserin) and Qsymia (combination of phentermine/topiramate in extended release.) These are not innocuous medications and significant side effects have been reported with each. Lorcaserin, an appetite suppressant (i.e. promotes satiety), is a drug that affects serotonin levels and as a result cannot, for example, be used with the many other medications that also affect serotonin levels because a life-threatening serotonin syndrome (e.g. agitation, hallucinations, incoordination, vomiting, and even coma) may develop. Furthermore, cognitive impairment (e.g. difficulty with memory and attention) and psychiatric symptoms (e.g. euphoria and even hallucinations) have been reported. Even concern about cardiac valvular disease, blood cell counts, and the risk of pulmonary hypertension have been mentioned, as has priapism (prolonged erection) in men. The combination drug Qsymia comes in different strengths and the dose is titrated up over time. The most common side effects are insomnia, constipation, dry mouth, dizziness, and parethesias, but cognitive impairment (including word-finding difficulties and problems with concentration) have also been noted. It should not be used with alcohol, and it is contraindicated in pregnancy as fetal abnormalities (e.g. cleft lip and palate) have been reported. Furthermore, weight loss is not dramatic with either medication and may not be sustained over years. 

For those who are obese, it is likely that more than one medication may be needed, analogous to the need for polypharmacy in hypertension or type II diabetes. One medication may be useful for weight loss while another may be necessary for weight maintenance over time. Eventually, it is possible that there will be available genetic screening to enable “personalized" medicine.

Unfortunately, there is no magic bullet for weight control. Michael Fumento, a medical journalist and author of The Fat of the Land, very wisely wrote, "...Americans by and large don't want a drug  that makes them eat less.  They want a drug that allows them to eat more but not gain weight." (p. 249) 

Sylvia R. Karasu, M.D., is Clinical Professor of Psychiatry at Weill Cornell Medical College and senior author of The Gravity of Weight.

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