Contrave: A promising new approach in the fight against obesity?

As a family physician whose practice deals exclusively in the treatment of obesity, it strikes me as remarkable how little we understand about the disease, which is Canada’s second-leading cause of preventable death.

In every region of the developed world, obesity doubled in the twenty years between 1988 and 2008, according to World Health Organization, which now count more than a half-billion of Earth’s population as obese. The Public Health Agency of Canada says obesity costs our nation somewhere between $4.6 billion to $7.1 billion annually. And yet, the most effective long-term therapy we’ve come up with to treat the disease is bariatric surgery — a comparatively radical procedure that sees a surgeon restrict the size of the stomach, or cut off a piece of it.

Recently, though, the fight against obesity is showing signs of joining the 21st century. For example, this autumn many in the medical profession expect the Food and Drug Administration in the United States to approve what I believe will be a really promising pharmaceutical therapy for obesity.

The drug’s development stems from an evolving understanding of a certain type of overeating that arises from stress-triggered depression.  The path to obesity may begin for some people with a stressful event the subject perceives as threatening — ranging from early life abuse to the loss of a job or a loved one. The resultant release of stress hormones interferes with the brain’s stimulus-reward circuitry. Essentially, the stress takes away one’s ability to feel pleasure. The resulting condition is referred to as “anhedonia.” one of two primary symptoms of depression.

The next step sees some anhedonia sufferers go off in search of other ways to activate their reward circuitry and feel pleasure. Most of the options remaining to them are unhealthy. Drugs and alcohol will get the job done, as can three substances that are vastly less regulated — sugar, salt and fat.

With few other options available to feel pleasure, the anhedonic person turns to the consumption of calorie-dense foods to fire the pleasure receptors. And over time, conditioning leads to a powerful drive to overeat—with stress and common settings like a couch and a TV triggering an overwhelming impulse to consume.

We live in a stressful world where we have virtually unlimited access to sugar, fat and salt — it’s available any time, nearly anywhere, super-sized and inexpensive. Throw stress at us and studies show that while 30% of us will lose weight, the remaining 70% will eat more and gain weight. Interestingly, 70% of Canadians are obese or overweight.

I have spent more than 12,000 hours treating obesity in the last 10 years and it is becoming increasingly apparent to me that this stress-anhedonia-overeating pathology may be contributing to the struggles of a majority of my patients.

Understanding that a link exists between stress, depression and obesity has begun to allow the pharmaceutical industry to tailor treatments to address the pathway. For example, a California-based company called Orexigen Therapeutics is in the final stages of seeking FDA approval for a drug it’s marketing under the name of Contrave. The pharmaceutical therapy actually is a combination of two drugs — an anti-depressant, buproprion, and naltrexone, an anti-addiction drug currently used to treat people for alcohol dependence. The buproprion alleviates the anhedonia that triggers the overeating, and in clinical trials, Contrave, combined with behavioral modification treatment, helped subjects lose an average of 10% of their body weight. And 10% weight loss is sufficient to treat early-stage diabetes. It’s expected to be approved by the FDA this fall, suggesting the possibility of a similar decision down the road by Health Canada. And other pharmaceutical therapies that combine anti-depressants with other drugs also are in the pipeline.

More exciting than any single drug, though, is the fact that the medical profession is developing new and more sophisticated behavioral and pharmaceutical ways to manage overeating. Will the new understanding stem the rise of obesity-related mortality? Could treatments based on our new understandings of why many overeat help you, or someone you know, address a developing weight problem?

The only certainty is that the medical profession needs more tools, in addition to surgery, to address the growing obesity epidemic — and with new behavioral and pharmaceutical treatments we, in my opinion, are getting them.

David Macklin is director, weight management program, Medcan ClinicThis article originally appeared in the National Post

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