Anti-Addiction, Obesity Drugs Tied to Depression a
> 4/25/2008 1:47:27 PM

Smoking and obesity are perhaps the world's two most prominent causes of preventable illness and early death. The promise of a pill that could curtail these destructive behaviors seems too good to be true, and several such drugs have been in development for years. Unfortunately, most remain mired in controversy, particularly after recent studies have again linked them to severe side effects like major depression and suicidality.

The diet drug rimonabant (Acomplia) perfectly illustrates this discouraging trend. It truly seemed to be a miracle drug in early trials, effectively combating patients' dependence on tobacco, decreasing appetites and promoting weight loss in obese individuals, and even counteracting addictions to alcohol and cocaine. Originally marketed primarily as a weight-loss drug and only tepidly endorsed as such by the FDA in 2006, it was denied approval as a smoking cessation aide. It was never actually formally approved for either purpose, and in the face of this new data the likelihood of its availability to the American public looks slim at best.

By suppressing the same cannabinoid receptors that create the highs and hunger pangs associated with marijuana use, the drug may effectively shut down the pleasure mechanisms in certain individuals' brains, and this reaction triggers an adverse response amounting to deep depression and, in extreme cases, suicidal thoughts. The numbers drawn from the latest rimonabant tests are not good: a full 43 percent of medicated study subjects reported adverse psychiatric effects compared to 28 percent of the placebo group. Most tragically, one of the medicated subjects comitted suicide during the study. Previous longitudinal studies found that, although individuals on rimonabant lost an average of 15 pounds per year, they were also three times more likely to discontinue the drug due to depression and anxiety than those on placebo. Researchers believe it's enough simply to state that this drug is not appropriate for those with histories of depression, but this insufficient explanation hardly accounts for the unflattering results of nearly every related study.

Anti-obesity drug taranabant looks likely to suffer the same fate. A similar CB-1 cannabinoid adherent/suppressant, the drug has helped patients lose up to 5% of their body weight when taken in large doses. Unfortunately, those doses have also created a disturbingly high rate of psychiatric disturbances in study subjects. Those taking the drug, as opposed to a placebo, in trial studies were twice as likely to drop out due to reports of severe depression and suicidal thoughts. The drug's makers plan to test it further and seek subsequent approval only for smaller doses, but this approach is obviously an attempt to minimize the problem and the volumes of bad press certain to follow. The fact that smaller doses produced almost none of the desired results also weighs against the drug's potential for approval.

The anti-smoking drug Chantix, the only one of these three that has actually been approved for public prescription by the FDA, has experienced similar problems since it went on sale. The drug doesn't operate on the same mechanism as the previous meds, but its use has likewise resulted in reports of depression and other psychiatric symptoms. Chantix has helped many users quit smoking; its success there is unquestioned. The current controversy instead swirls around side-effects that are experienced by a small, but significant number of users. In the face of warnings issued by the FDA as well as renewed examination by the organization, Chantix will likely not emerge unscathed, and that will be the right decision if the drug is found to be too hazardous. It's important to note the chicken-or-egg dilemma smoking cessation with Chantix presents. Not only are depressed individuals more likely to smoke (possibly due to antidepressant properties of tobacco) and smokers considerably more likely to be depressed, but depressive individuals also often find it much harder to quit smoking once they've started. In fact, mood swings, anger and anxiety are very common symptoms of smoking cessation, especially that of the cold turkey variety.

Unfortunately, the overwhelming presence of psychatric side-effects among the subjects testing these medications cannot be entirely attributed to the emotional disturbances common to addiction and obesity. The super-pill approach may simply have proven itself implausible for the time being. Developers may also have to scrap the cannabinoid repressant strategy entirely as it too often produces unwanted results and we simply don't seem to know enough about the way in which such drugs affect the brain. We can only hope, of course, that the successes that some have observed on these drugs lead to the creation of more efficient medications in the near future.

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