Background: Sex differences in regards to pharmacotherapy for alcoholism is a topic of concern following publications suggesting naltrexone, one of the longest approved treatments of alcoholism, is not as effective in women as in men. This study was conducted by combining 2 randomized placebo controlled clinical trials utilizing similar methodologies and personnel in which the data was amalgamated to evaluate sex effects in a reasonable sized sample.
Methods: A total of 211 alcoholics (57 female and 154 male) were randomized to the naltrexone/cognitive behavorial thearpy (CBT) or placebo/CBT arm of the 2 clinical trials analyzed. Baseline variables were examined for differences between sex and treatment groups via ANOVA for continuous variable or chi-squared test for categorical variables. All initial outcome analysis was conducted under an intent-to-treat analysis plan. Effect sizes for naltrexone over placebo were determined by Cohen's D (d).
Results: The effect size of naltrexone over placebo for the following outcome variables was similar in men and women [% days abstinent (PDA) d = 0.36, % heavy drinking days (PHDD) d = 0.36, and total standard drinks (TSD) d = 0.36]. Only for men were the differences significant secondary to the larger sample size (PDA p = 0.03; PHDD p = 0.03; TSD p = 0.04). There were a few variables (GGT at week-12 change from baseline to week-12: men d = 0.36, p = 0.05; women d = 0.20, p = 0.45 and drinks per drinking day: men d = 0.36, p = 0.05; women d = 0.28, p = 0.34) where the naltrexone effect size for men was greater than women. In women, naltrexone tended to increase continuous abstinent days before a first drink (women d = 0.46, p = 0.09 and men d = 0.00, p = 0.44).
Conclusions: The effect size of naltrexone over placebo appeared similar in women and men in our hands suggesting the findings of sex differences in naltrexone response might have to do with sample size and/or endpoint drinking variables rather than any inherent pharmacological or biological differences in response.