There are three main therapies that are and were highlighted this year.  This article focuses on Contrave while also discussing briefly the other two, lorcaserin and Qnexa.

Contrave is a new treatment for obesity that consists of Wellbutrin sustained release combined with Naltrexone instant release.

It has shown modest efficacy to date, which was likely overstated, and concerns remain as to whether the addition of Naltrexone to Wellbutrin really causes that much weight loss.

Wellbutrin is a popular antidepressant that has a variety of effects, including some stimulatory ones that may help induce weight loss.  It is, for instance, eventually converted by the body to a form of amphetamine.  Naltrexone is an opioid antagonist that is used mainly for treating addiction.

The biochemical theory of action is as follows: Wellbutrin has been shown to have an effect on the pro-opiomelanocorin (POMC) pathway in the brain that works to suppress appetite.  Activation of this pathway leads to the release of alpha-MSH and beta-endorphin.  The alpha-MSH induces weight loss, while the beta induces tolerance to this effect via opioid receptors.

Some say that the reason Wellbutrin as a treatment by itself doesn’t cause such great weight loss is because of this tolerance.  That’s where naltrexone comes it.  It blocks the opioid activity of this pathway, which should, in theory, keep it working for a long time.

The efficacy data for Contrave does not clearly demonstrate efficacy superior to monotherapy with Wellbutrin alone in all studies.  Additionally, some of the data published on Contrave’s efficacy were overstated due to an ‘accidental’ clerical error.

Lorcaserin is a serotonergic receptor acting agent that promotes feelings of fullness.  It has shown modest albeit limited efficacy in most studies, with people on it losing slightly more weight than people on placebo.

The main concerns around it are: a) its limited efficacy b) its potential for side effects including possibly carcinogenicity and heart damage

Because of these concerns, it was not approved by the FDA.

Qnexa is a combination of phentermine and topiramate, a medication related to stimulants and a medication for the treatment of epilepsy and some other conditions.  It worked great, with a high percentage of those taking it losing a significant amount of weight.

The main concern was again of safety.  Phentermine was part of the fen-phen combination which was removed from the market.  As such, the safety concerns raised around it are unusually meaningful and led to its negative reception.