With its unique mechanism of action in the CNS, Contrave has the potential to change the way obesity is treated by:

Initiating weight loss by reducing appetite and increasing metabolism.  Allowing the body to sustain continued weight loss by offsetting its natural tendency to fight back and slowing down the weight loss process.  Addressing the reward system in the brain that causes food cravings

Contrave is a combination of two well-established drugs, bupropion and naltrexone, in a sustained release formulation (SR).

The active ingredients of Contrave have been used for over 20 years.  Bupropion is a widely-prescribed antidepressant and smoking cessation medication; naltrexone is a treatment for alcohol and opioid addiction.  We believe that bupropion helps initiate weight loss while naltrexone may sustain weight loss by preventing the body’s natural tendency to counteract efforts to lose weight. ↩

The drug is Contrave, from Orexigen Therapeutics Inc. It’s a combination of two existing drugs: The antidepressant Wellbutrin and the addiction drug naltrexone.

Contrave doesn’t work in the belly. It works in the hypothalamus, the brain’s central thermostat that controls appetite, temperature, and how the body burns energy.

It’s already known that people lose weight soon after starting Wellbutrin treatment. But this effect soon wears off, and people regain weight. That’s where the naltrexone comes in, says endocrinologist Dennis D. Kim, MD, MBA, Orexigen’s senior vice president for medical affairs.

“Naltrexone comes in and lifts the brake on the Wellbutrin effect,” Kim tells WebMD. “So you have a synergistic effect to signal the hypothalamus to reduce food intake. Weight decrease is maintained over time.”

That sounds good in theory. But does it work?

The drug was tested in a clinical trial that enrolled nearly 700 obese people — 90% of them women, with an average weight of 223 pounds. All study participants enrolled in an intensive weight loss program that included counseling, diet, and exercise. Two-thirds of the study participants also took Contrave.

Just under 60% of the participants stayed in the program for 56 weeks.

The intensive weight loss program worked well. After 56 weeks, they had an overall weight loss of just over 5% of their body weight — 11 to 16 pounds. Moreover, 11% of participants who finished the study lost more than 15% of their body weight.

But those who took Contrave did even better. After 56 weeks, they lost 9.3% of their body weight — 20 to 25 pounds. And more than 29% of them lost more than 15% of their body weight.

Nausea, usually mild or moderate, was a frequent side effect of Contrave treatment. More patients on Contrave also reported mild-to-moderate headaches and constipation. All these side effects tended to occur early in the study.

Despite the side effects, patients on Contrave did not suffer worsening depression or psychiatric symptoms. In fact, they reported better quality of life than other participants.

Clearly, any weight loss drug will work better when combined with a state-of-the-art weight loss program. Additional studies are looking at how well Contrave works when combined with less drastic programs.

“We don’t expect an intensive diet and exercise program to be needed in order for Contrave to work well,” Kim says.

Contrave isn’t the only weight loss drug Orexigen has in the works. The company is also testing another pill, Empatic, that combines Wellbutrin with the seizure drug Zonegran. In early clinical studies, obese patients lost 10% of their body weight in six months. More study results should be available by the end of this year.

Thomas Waden, PhD, of the University of Pennsylvania’s Center for Weight and Eating Disorders, presented the Orexigen study findings in a presentation to the annual meeting of the American Diabetes Association, held June 6-9 in New Orleans. ↩