Efficacy and safety of baclofen for alcohol dependence: a randomized, double-blind, placebo-controlled trial.
BACKGROUND
Recent clinical trials and case-reports indicate that baclofen, a GABA(B) agonist, may have efficacy for alcohol dependence. Baclofen has been shown to enhance abstinence, to reduce drinking quantity, to reduce craving, and to reduce anxiety in alcohol-dependent individuals in 2 placebo-controlled trials in Italy. However, the clinical trial data with baclofen is limited. The purpose of the present study was to test the efficacy and tolerability of baclofen in alcohol dependence in the United States.


METHODS
The study was a double-blind, placebo-controlled, randomized study comparing 30 mg/d of baclofen to placebo over 12 weeks of treatment and utilizing 8 sessions of BRENDA, a low-intensity psychosocial intervention. One hundred and twenty-one subjects were screened to yield 80 randomized subjects (44 men) with randomization balanced for gender. Percent heavy drinking days was the primary outcome measure with other drinking outcomes, anxiety levels, and craving as secondary outcomes. Tolerability was examined.


RESULTS
Seventy-six percent of subjects completed the study. No difference by drug condition was seen in percentage of heavy drinking days where on-average rates were 25.5% (±23.6%) for placebo and 25.9% (±23.2%) for baclofen during treatment (t(73)=0.59, p=0.56). Similarly, no differences were seen by drug condition in percentage of days abstinent, time to first drink, or time to relapse to heavy drinking. Baclofen was associated with a significant reduction in state anxiety (F(1,73)= 5.39, p=0.02). Baclofen was well tolerated with only 2 individuals stopping baclofen because of adverse events. There were no serious adverse events.


CONCLUSIONS
Baclofen, a GABA(B) agonist, represents a possible new pharmacotherapeutic approach to alcohol dependence. Despite encouraging preclinical data and prior positive clinical trials with baclofen in Italy, the current trial did not find evidence that baclofen is superior to placebo in the treatment of alcohol dependence. Additional clinical trial work is necessary to establish whether baclofen does or does not have therapeutic efficacy in alcohol dependence and, if it does, what factors are predictive of response.
Garbutt
James C
JC
Department of Psychiatry, University of North Carolina at Chapel Hill, CB#7160, Chapel Hill, NC 27599-7160, USA. jc_garbutt@med.unc.edu
Kampov-Polevoy
Alexei B
AB
Gallop
Robert
R
Kalka-Juhl
Linda
L
Flannery
Barbara A
BA
D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy / Q000523:psychology; D000437:Alcoholism / Q000188:drug therapy* / Q000523:psychology; D001007:Anxiety / Q000150:complications / Q000523:psychology; D001418:Baclofen / Q000009:adverse effects / Q000627:therapeutic use*; D003863:Depression / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D018755:GABA Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D012008:Recurrence; D012727:Sex Characteristics; D012959:Socioeconomic Factors; D016896:Treatment Outcome; D055815:Young Adult
D018755:GABA Agonists; D001418:Baclofen