Exploring the impact of gender and reproductive status on outcomes in a randomized clinical trial of naltrexone augmentation of nicotine patch

In a series of exploratory analyses, we examined the roles of gender, reproductive status and negative affect on smoking abstinence in subjects participating in a large (n = 385) 6-week randomized clinical trial (RCT) of nicotine patch therapy, with varying doses of oral naltrexone (0 mg, 25 mg, 50 mg, 100 mg) treatment. Negative affect was assessed daily during the first post-quit week via telephone interactive voice response (IVR). Weight and adverse events were recorded weekly. In the intent to treat sample, the effects of dose on continuous abstinence were non-significant in the overall model for men and women. In the 295 study completers, there was a significant effect of dose on continuous abstinence in women only (F = 8.53, p = 0.04). In the 100 mg group, 71% of women were continuously abstinent compared to 41% in the placebo group (p < 0.05). Women in the active naltrexone groups gained less weight (F = 2.91, df = 3, p = 0.04). Women in the 100 mg vs. placebo group were less adherent with medication (F = 3.19, p < 0.05). These effects were not significant in men. Naltrexone treatment condition (100 mg vs. placebo, p = 0.02, odds ratio (OR) = 0.28), gender (OR = 0.55 p = 0.09), and IVR ratings of negative affect (OR 1.02, p = 0.04) predicted abstinence at Week 1 in study completers. Menstrual cycle status on quit day had a modest affect on abstinence. These data suggest that naltrexone dose, gender, and negative affect play a role in smoking abstinence, particularly in the early stages of treatment. When used in conjunction with nicotine replacement therapy, naltrexone dose may be important in women.