Naltrexone Reduction of Long-Term Smoking Cessation Weight Gain in Women But Not Men: A Randomized Controlled Trial

Background: The opioid antagonist naltrexone has shown promise to reduce weight gain during active treatment, but longer-term studies have not been conducted. The goal was to examine effects of naltrexone on weight gain over long-term follow-up in men and women who quit smoking. Methods: Weight was examined at baseline and 6- and 12-month follow-up in the two largest randomized, double-blind, placebo-controlled trials of naltrexone in nicotine dependence. For 6-12 weeks after the quit date, participants were randomly assigned to receive naltrexone or placebo. Behavioral counseling and open-label nicotine patch were also included for the first 4-6 weeks. Of the 700 participants in the combined intent-to-treat sample, there were 159 (77 women) biochemically verified abstinent smokers at 6 months, and 115 (57 women) of them remained abstinent at 12 months. Changes in weight (in kilograms or in percentage) and body mass index from baseline to the follow-ups were assessed for these participants. Results: Weight gain was significantly lower for women treated with naltrexone compared with placebo (6 months, 3.3 vs. 5.5 kg; 12 months, 5.9 vs. 7.4 kg, respectively). Increases in body mass index and percentage body weight gain were also significantly lower in women treated with naltrexone versus placebo. These effects were not observed in men. Conclusion: The results provide evidence for naltrexone as the first pharmacotherapy to reduce postsmoking cessation weight gain among women.