The safety and efficacy of baclofen to reduce alcohol use in veterans with chronic hepatitis C: a randomized controlled trial

Background and Aims: Alcohol use disorders (AUDs) are common among people with chronic hepatitis C (HCV) and accelerate the development of fibrosis and cirrhosis caused by HCV. Baclofen, a gamma-aminobutyric acid (GABA) beta-receptor agonist, differs from medications for AUDs currently approved by the United States Food and Drug Administration (FDA), as it is metabolized primarily through the kidneys. The primary outcome of this study was to compare baclofen with a placebo in the percentage of days abstinent from alcohol. Design: A double-blind, placebo-controlled randomized trial. Setting: Hepatology clinics in four separate US Veteran Affairs Medical Centers in the United States. Participants: One hundred and eighty Veteran men and women older than 18 years with chronic HCV, a comorbid AUD and current alcohol use. Intervention and Comparator: Oral baclofen was given at dosages of 0 (placebo) or 30 mg/day over 12 weeks with concomitant manual-guided counseling. Measurements: The primary measurement was percentage of days abstinent during the 12-week study period between the baclofen and placebo groups [measured by time-line follow-back (TLFB)]. Secondary measurements were the percentage of Veterans who achieved complete abstinence, the percentage of Veterans who achieved no heavy drinking between weeks 4 and 12 of the study, alcohol craving, anxiety, depression and post-traumatic stress disorder (PTSD). Findings: Primary outcome: compared with placebo, baclofen did not improve the percentage of days abstinent. For all subjects there were significant reductions from baseline to 12 weeks in percentage of days abstinent from 37.0% [standard error (SE) = 2.7] to 68.6% (SE = 2.8, F_(1151.1) = 66.1, P < 0.001). However, there was no statistically significant difference between groups for change in percentage of days abstinent over the 12-week study period [absolute difference 1.3% (−9.1 to 1.7%), F_(1152.6) = 0.005, P = 0.95]. Secondary outcomes: Of subjects who completed the first 4 weeks of the study, 8.9% (15 of 168) achieved complete abstinence; 10.1% (nine of 89) in the placebo group and 7.6% (six of 79) in the baclofen group [χ² ₍₁₎ = 0.33, odds ratio (OR) = 0.73 (0.24–2.15)]. The percentage of no heavy drinking for all subjects between weeks 4 and 12 was 20.2% (34 of 168), but no statistically significant differences were found between placebo 15.7% (14 of 89) and baclofen 25.3% (20 of 79) [χ² ₍₁₎ = 2.38, OR = 1.82 (0.85–3.90)]. There were significant reductions for all subjects in all other secondary variables over the course of the study, but no differences between groups. Measures of various biomarkers of alcohol use did not change significantly throughout the course of the study for either the baclofen or placebo groups. Conclusions: Baclofen administered at 30 mg/day does not appear to be superior to placebo in increasing abstinence or in reducing alcohol use, cravings for alcohol or anxiety among people with alcohol use disorder.