Naltrexone, bupropion combination helps individuals lose excess weight

August 17, 2010

Investigational combination treatment with sustained-release (SR) naltrexone and bupropion (Contrave, Orexigen Therapeutics) combined with lifestyle modification, appears effective in helping people lose 5% or more of their excess body weight, according to research published online July 30 in The Lancet and reported by HealthDay News.

Investigational combination treatment with sustained-release (SR) naltrexone and bupropion (Contrave, Orexigen Therapeutics) combined with lifestyle modification, appears effective in helping people lose 5% or more of their excess body weight, according to research published online July 30 in The Lancet and reported by HealthDay News.

Frank L. Greenway, MD, of the Louisiana State University System in Baton Rouge, and colleagues randomly assigned 1,742 individuals aged 18 to 65 with a body mass index (BMI) of 30 to 45 kg/m² and uncomplicated obesity, or BMI of 27 to 45 kg/m² with comorbidities, to a mild hypocaloric diet and exercise, along with either SR naltrexone 32 mg daily plus SR bupropion 360 mg daily, SR naltrexone 16 mg daily plus SR bupropion 360 mg daily, or placebo. Trial patients received the oral medication or placebo twice daily for 56 weeks.

Of the 1,453 participants included in the final analysis, 48% taking naltrexone 32 mg plus bupropion, 39% taking naltrexone 16 mg plus bupropion, and 16% of those on placebo lost 5% or more of their body weight.

Those receiving the combination therapies were more likely than the placebo group to experience headaches, constipation, dizziness, vomiting, and dry mouth. Nausea was experienced by 29.8% of participants in the naltrexone 32-mg group, 27.2% in the naltrexone 16-mg group, and 5.3% in the placebo group. The combination treatment groups also experienced a transient increase in blood pressure of about 1.5 mmHg and then a drop of about 1 mmHg below baseline.

Dr. Greenway told Drug Topics the research is critical for 2 reasons. One is that bupropion-naltrexone is a combination drug and the other is that it addresses cravings.

“We presently have only two medications approved for the long-term treatment of obesity,” he said. “Putting the two together does not result in additive weight loss. Other chronic diseases like diabetes and hypertension use combination drug therapy. If one antihypertensive drug does not give a sufficient drop in blood pressure, one adds another until the goal of a normal blood pressure is met. The combination of bupropion and naltrexone gives weight loss that is more than one gets by adding the weight loss of bupropion alone to the weight loss with naltrexone alone. Thus, naltrexone-bupropion is bringing obesity into an era of combination drugs that already has had great success in treating diabetes and hypertension.”

As for cravings, Dr. Greenway said that most medications for obesity have targeted the appetite centers in the brain. Naltrexone and bupropion do this too, but they also target the reward system, which is new.

“Bupropion is used to help people who want to stop smoking and naltrexone is used to help those that are addicted to cocaine or alcohol,” he said. “Thus, the combination of naltrexone and bupropion may be particularly helpful for those people who find that their cravings interfere with their ability to stay on a weight-loss diet.”

Dr. Greenway said it is important that FDA approve a drug for the treatment of obesity.

“The obesity field needs more options for treatment,” he said. “So, naltrexone-bupropion and the other drugs with new drug applications pending at FDA will all be very important to the effective treatment of obesity with medications.”

Eight authors disclosed financial and other ties to pharmaceutical and/or medical device companies, including Orexigen Therapeutics, which provided funding for the study. One author holds 3 patents for treatment-related obesity.