Naltrexone may augment the effects of the nicotine patch for smoking cessation, according to the results of a double-blind, dose-ranging study reported in the March 27 issue of the Archives of Internal Medicine. As an added benefit in some patients, low-dose naltrexone therapy may also lead to weight reduction.

"Many smokers remain refractory to current therapies, which only partially address weight gain after smoking cessation," write Stephanie S. O'Malley, PhD, from Yale University School of Medicine in New Haven, Conn, and colleagues. "This study evaluated whether naltrexone hydrochloride augmentation of nicotine patch therapy improves smoking abstinence and reduces postcessation weight gain more than nicotine patch therapy alone and at what dose."

At an outpatient research center, 400 individuals who smoked 20 or more cigarettes daily were randomized to treatment for 6 weeks with a 21-mg nicotine patch and oral naltrexone (0, 25, 50, or 100 mg/day) Follow-up was for 1 year after randomization. The a priori specified main outcomes were prolonged 4-week cigarette abstinence after a 2-week grace period in the intent-to-treat sample, and weight gain in these abstainers.

In the intent-to-treat analysis, there were no significant differences in prolonged 4-week abstinence (P = .49) or 6-week continuous abstinence after the quit date (P = .12) during treatment. In 295 participants who completed treatment, the 100-mg dose was associated with higher continuous abstinence rates (71.6%) than was placebo (48%; odds ratio, 2.73; 95% confidence interval, 1.39 - 5.39; P < .01).

In the group of continuous abstainers, those receiving 25 mg of naltrexone gained significantly less weight (mean, 0.7 ± 0.31 kg) than did the placebo group (1.9 ± 0.33 kg; P < .01). Participants with prolonged abstinence and treatment completers had similar naltrexone dose effects on weight.

"The 100-mg dose of naltrexone hydrochloride appears the most promising for augmenting the efficacy of the nicotine patch on smoking cessation outcomes but requires further study," the authors write. "The significant weight reduction with low-dose naltrexone therapy suggests that it may be useful as a second-line treatment for weight-concerned smokers."

Study limitations are that the results of the treatment completer analysis must be interpreted cautiously, given the lack of significant effects in the intent-to-treat sample; possible inflation of smoking abstinence rates due to undetected smoking lapses; limited generalizability because of recruitment via advertisements and press releases, and predominantly white sample; insufficient power to detect effects on posttreatment outcomes; short duration of treatment; and type I error.

"The results of this dose-ranging study provide support for further testing of the efficacy of the 100-mg dose for smoking cessation," the authors conclude. "In the meantime, the benefit of low-dose naltrexone therapy on reducing weight gain may have immediate clinical utility for the subset of weight-concerned smokers."

The National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcohol Dependence, National Institutes of Health, the Robert Wood Johnson Foundation, and the Department of Veterans Affairs, Newington, Conn, supported this study. GlaxoSmithKline Inc, donated nicotine patches. Three authors have disclosed they are coinventors on a patent held by Yale University for smoking cessation treatments using naltrexone and related compounds. Several authors have disclosed relevant financial relationships with Alkermes Inc, the maker of an investigational injectable naltrexone; DuPont, the maker of naltrexone; GlaxoSmithKline Inc; Forest Laboratories; Lipha Pharmaceuticals; Ortho-McNeil, Inc; Bristol-Myers Squibb; Pfizer Inc; Sanofi-Aventis; Mallinckrodt Pharmaceuticals; and Johnson & Johnson.