Psychiatric Drug Combination Approved for Weight Loss

When creating new colors, school children know that yellow and blue combine to make green; when creating novel pharmacotherapies, researchers have used a similar approach. The newest result for psychiatry is Contrave, approved last month by the Food and Drug Administration (FDA) for weight loss. This medication is a combination of naltrexone and bupropion extended release.

Contrave is the third medication approved by the FDA for weight loss. Naltrexone is an opioid receptor antagonist approved for the management of alcohol dependence and opioid dependence, and bupropion extended release is a weak norepinephrine-dopamine reuptake inhibitor approved as an antidepressant and pharmacological smoking-cessation aid. The new treatment option, manufactured by Takeda, is intended for people with a body mass index (BMI) of 30 or greater (obesity) or a BMI of 27 or greater (overweight) with one weight-related condition such as hypertension, type 2 diabetes, or hypercholesterolemia.

“Obesity continues to be a major public health concern,” said Jean-Marc Guettier, M.D., director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research. “When used as directed in combination with a healthy lifestyle that includes a reduced-calorie diet and exercise, Contrave provides another treatment option for chronic weight management.”

The effectiveness of Contrave was measured in multiple clinical trials with approximately 4,500 obese and overweight individuals, with and without significant weight-related conditions. All participants were on a reduced-calorie diet and a physical activity regimen.

Results in a trial with nondiabetic patients showed that 42 percent of participants taking Contrave were able to shed at least 5 percent of their body weight in a year, while only 17 percent of patients treated with placebo were able to do so. In a clinical trial with diabetes patients, those taking the combination drug were twice as likely to lose 5 percent of their body weight within a year than were control subjects. The most common adverse reactions reported included nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.

Because the medication contains bupropion, it has a boxed warning for increased risk of suicidal thinking and behavior and serious neuropsychiatric events. The exact neurochemical effects of the drug leading to weight loss are not yet fully understood, according to Takeda.

In an interview with Psychiatric News, Petros Levounis, M.D., M.A., chair of psychiatry at Rutgers New Jersey Medical School, said that approval of a novel pharmacological approach to treat obesity is one that should be applauded, since obesity is a public health issue that is critical for both physical and mental health.

“While the exact mechanism of action of the naltrexone/bupropion combination has not been elucidated, each drug has a proven success record in addiction treatment: bupropion for tobacco and naltrexone for alcohol and opioid use disorders. As we are starting to conceptualize food—and specifically sugar—as a bona fide addictive substance, Contrave has the potential of being a game changer in our battle against obesity.”

The FDA will further access the safety of Contrave by requiring the following postmarket studies:

Takeda plans to commercially launch Contrave by the end of the year. ■