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

Abstract

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 (0mg, 25mg, 50mg, 100mg) 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 100mg 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 100mg vs. placebo group were less adherent with medication (F=3.19, p<0.05). These effects were not significant in men. Naltrexone treatment condition (100mg 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.