Two phase III studies have found that a combination of naltrexone SR/bupropion SR can produce weight loss in overweight and obese women, regardless of menopausal status. The two-drug formulation is being developed as the experimental anti-obesity drug Contrave.

One of the studies compared two formulations of the drug to placebo in 1482 women, just under half of whom completed the 56-week study in each treatment group. The intent-to-treat analysis found women given 32 mg naltrexone plus 360 mg bupropion lost 6.2% of their mean body weight, compared to 5.3% for women on the lower-dose formulation (16 mg naltrexone plus 360 mg bupropion). Women in the placebo group lost 1.2%. Researchers also reported that women who received Contrave "had improved responsiveness to their food cravings and had an easier time controlling what they were eating." A per protocol analysis showed that women in the treatment groups lost 7 to 8% of their body weight. In the other study, 32 mg naltrexone/360 mg bupropion formulation was compared to placebo in 713 women, all of whom also received 28 group sessions of counseling on diet, exercise and behaviour. Overall, 58% of the women completed the study. At 56 weeks, the women in the treatment group had lost 9.8% of their mean body weight, compared to 5.7% for women in the placebo group (no statistical data available from Reuters report). Both studies found greater improvements in weight-related quality of life for the women in the treatment groups than for women on placebo. All effects were similar for pre- and peri- and postmenopausal women. In both studies, the most frequent side effects were nausea, headache and gastrointestinal side effects.

In February 2011, the FDA declined to approve the drug, Contrave as there was concern about the link to increased pulse rate and blood pressure, and the company was asked to conduct a long-term clinical trial to show that treatment would not increase the risk of heart attacks.