Addiction Drug for Obesity?

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This week, Orexigen, a biopharmaceutical company in La Jolla, CA, announced that it won a patent covering its obesity drug Contrave. Contrave actually consists of a sustained-release version of two older drugs: bupropion, which is currently used as an antidepressant and smoking cessation aid, and naltrexone, which is used for opioid addiction and alcoholism. Contrave is currently undergoing Phase III trials for obesity and the company hopes to file for FDA approval in late 2009. Why is Contrave, a combination of two drugs that have been around for a while, novel? Firstly, there is no doubt that depression is a common problem in treatment-seeking obese individuals, many of whom are “self-medicating” with food – i.e. eating highly palatable foods that increase serotonin levels in the brain to improve their mood (albeit temporarily). There is indeed evidence that buproprion may help some people lose weight. Secondly, many patients with obesity will be the first to admit that for them eating is akin to an addiction – a statement that is not surprising given that opioid-mediated reward mechanisms may play an important role in the hedonic aspects of ingestive behaviour and that this behaviour may well involve exactly the same neurocircuitary that plays a role in other addictions. So the idea of combining two drugs that address depression and addiction, respectively, is certainly one with merit and may well prove to be highly effective in obese patients in whom depression and hedonic eating are significantly contributing to hyperphagia. I have not seen data from these trials and have no relationship with Orexigen. I do however, like the concept of this drug and can’t wait to try it on some of my patients, who I can well imagine would benefit. Obviously, we need to await the results of the Phase III program and certainly need to very carefully look at the side effect profile of the two drugs used in combination. But I do think that this could indeed be a useful drug for some patients battling obesity – although it is unlikely to be the “magic bullet” for everyone. Remember, obesity is a highly complex and heterogeneous disorder and there is absolutely no reason why any one treatment should work for all. AMSEdmonton, Alberta

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If You Think You’re Too Big – You May Get Depressed

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There is a widespread notion that obesity and depression go hand in hand. This is not true. In fact, thin people are as likely to get depressed as people with overweight or obesity. However, depression rates are higher in people who are trying to lose weight, particularly in those seeking help to do so. So why is there more depression in the latter group? One explanation, according to Evan Atlantis and Kylie Ball from the University of Sydney, published in the International Journal of Obesity, may be that dissatisfaction with your weight may increase your risk for psychological distress and thus depression. Atlantis and Ball conducted a cross-sectional study on data from 17,253 individuals participating in the Australian National Health Survey 2004-2005. All variables, including weight status, weight perception and scores for psychological distress were collected by self-report. Overweight and underweight perception increased the odds of psychological distress, whereas the actual weight status did not. This finding applied to both genders. The authors conclude that people who perceive themselves as over- (or under-) weight are more likely to have psychological distress that may promote depression than people who do not fuss about their weight. Whether or not this perception is actually changed by weight loss (or weight gain) remains to be seen. AMSEdmonton, Alberta

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