Arya M. Sharma, MD

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

Posted by Arya M. Sharma, MD, at 6:44 AM  
Labels: addiction, treatment

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