Studies on new pharmacological treatments for alcohol dependence - and the importance of objective markers of alcohol consumption

Abstract

This thesis will guide you through three randomized controlled trials (RCT) on three pharmacotherapies for alcohol dependence; the antidepressant drug mirtazapine, the smoking cessation drug varenicline and the glycine-uptake inhibitor Org 25935. The mirtazapine study was an investigator initiated single-center harm-reduction study with alcohol consumption measured by self-report in a diary as main outcome. The results indicated that mirtazapine reduced alcohol consumption in males with heredity for alcohol use disorder (AUD). The Org 25935 study was an international multi-center study with abstinence as treatment goal, main time to relapse and alcohol consumption was measured by self-report collected by the Time Line Follow Back method (TLFB). All subjects reduced their drinking compared to baseline, but Org 25935 failed to show superiority over placebo. The varenicline study was an investigator initiated multi-center harm-reduction study. In this study alcohol consumption was measured both by self-report in a diary and by alcohol biomarkers. In the analysis of self-reported data, varenicline failed to show efficacy, however, in the biomarker analysis varenicline reduced alcohol consumption compared to placebo. The direct alcohol marker phosphatidylethanol (PEth) was superior to the indirect biomarkers CDT and GGT in measuring alcohol consumption.