Dr. Sharma's Obesity Notes

Yesterday, I was widely quoted in national media on the issue of food addiction. The background for this was an interview done by CanWest’s Sharon Kirkey regarding a recent paper by Simon Thronley and colleagues from Auckland, New Zealand, published in Medical Hypothesis.

The basic tenor of their article is that food consumption shows many similarities to features of other addictive behaviours, such as automaticity and loss of control. They hypothesize that Glycemic Index (GI) is perhaps the key element of food that predicts its addictive potential.

They quote reports of a withdrawal syndrome from high glycemic food abstinence and argue that both empirical and clinical studies support an addictive component of eating behaviour, with similar neurotransmitters and neural pathways triggered by food consumption, as with addictive drugs.

Specifically, they argue that the short time to peak arterial concentration of glucose (similar to the short time to peak concentrations of nicotine in smokers) associated with high GI-foods, essentially ’spikes’ the addictive potential of palatable foods - thereby making them more addictive than low-GI foods.

The authors suggest that subtle changes in the preparation and manufacturing of commonly consumed food items and/or reducing glycemic index through regulatory channels, may help break a cycle of [food-] addiction and draw large public health benefits.

While I much like their concept, and certainly buy into the fact that some folks demonstrate features akin to food addiction, this is certainly not a universal thruth that applies to all people with excess weight - in fact, I know a couple of normal weight people, who probably have “sweet addiction” as well.

Nevertheless, I do think that this paper should once again remind us of the important mental health component to ingestive behaviour and certainly explains why for some people kicking doughnuts and chocolate is apparently as hard as kicking alochol or cocaine.

AMS
Edmonton, Alberta.

I have often blogged on the close link between certain forms of obesity and addiction. Not only do many patients battling with obesity openly admit to a “food addiction”, several drugs targeting obesity such as rimonabant (a CB-1 receptor antagonist) or contrave (a combination of buproprion and naltrexone) specifically target the neurocircuitary of the brain’s addiction system.

A new addition to this approach may be Gaba-vinyl-GABA (GVG) or vigabatrin, an epilepsy drug currently undergoing Phase II trials for patients with cocaine and methamphetamine dependence.

In a study published by Amy deMarco and colleagues from Brookhaven National Laboratory, Upton, NY, in the journal Synapse last week, vigabatrin resulted in a dose-dependent 12-20% reduction in body weight in Sprague Dawley and adolescent and adult Zucker fatty rats.

Vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the catabolism of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. The mechanism of action of vigabatrin is attributed to irreversible enzyme inhibition of GABA-T, and consequent increased levels of the inhibitory neurotransmitter, GABA.

Vigabatrin is sold as Sabril in Canada by Ovation Pharmaceuticals Inc for the adjunctive management of epilepsy which is not satisfactorily controlled by conventional therapy.

Its major neurological side effects include somnolence, impairment of peripheral vision and risk for seizures. Increases in liver enzymes have also been reported.

No doubt, it will be interesting to see how the clinical trials of this compound for obesity pan out. Apparently, Brookhaven Labs have licensed out the compound to Catalyst Pharmaceutical Partners, (Coral Gables, Florida), who plan to test it for binge-eating disorder (BED).

I am not sure why exactly the researchers (and Catalyst Pharmaceuticals) believe that BED is the best population to test this in, as this disorder (as blogged before) readily responds to CBT and does not actually present with typical features of addiction. In fact one of the key features of BED, the sense of dispair and failure that follows a binge episode is the exact opposite of a “high” experienced by drug users.

In any case, to me, patients with BED seem the least likely obese population to respond to an addiction drug - but who knows, we’ll find out soon enough (always happy to eat my words).

AMS
Edmonton, Alberta

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.

AMS
Edmonton, Alberta