World Health Organization risk drinking levels as a treatment outcome measure in topiramate trials.

BACKGROUND Although abstinence has traditionally been considered the only suitable outcome for alcohol treatment, reduced drinking is also associated with improved functioning and medical and psychiatric outcomes. The World Health Organization (WHO) risk drinking levels (RDLs) have been shown to be valid outcome measures in treatment trials for alcohol use disorder (AUD). METHODS We conducted a secondary analysis of two 12-week, randomized controlled trials (RCTs), in which a total of 308 individuals with problematic alcohol use received topiramate or placebo treatment. We compared the utility of the WHO RDLs with other treatment outcomes, including self-reported measures of alcohol consumption, alcohol-related problems, and quality of life, and the biomarker gamma-glutamyltransferase. RESULTS Topiramate treatment was associated with small effect sizes for both a 1-level (d = 0.26) and a 2-level (d = 0.19) reduction in WHO RDL, effects that were not significant after correction for multiple comparisons. No heavy drinking days, one of the outcome measures recommended by the US Food and Drug Administration for alcohol medication registration trials, also exhibited a small effect (0.21), while an effect size for abstinence could not be calculated. There were medium effects of topiramate on continuous measures of percent heavy drinking days (d = 0.49) and alcohol-related problems (d = 0.41). CONCLUSIONS Topiramate is an efficacious pharmacotherapy for AUD. Although continuous measures of drinking and alcohol-related problems yielded larger effect sizes than the WHO RDLs, the latter nonetheless provide a categorical alternative for use in both clinical care and pharmacotherapy trials.