Journal reference: Garbutt JC, Kampov-Polevoy AB, Gallop R, Kalka-Juhl L, Flannery BA. Efficacy and safety of baclofen for alcohol dependence: a randomized, double-blind, placebo-controlled trial. Alcohol Clin Exp Res 2010 Nov;34(11):1849-57
Published: November 2010
|Baclofen cannot be recommended as a routine treatment for alcohol use disorders
This article was published in the November 2017 edition of Medical Observer, under the title, “A panacea for alcohol cravings” (pp. 60-61). (PDF)
Jorge, an unemployed 35-year-old factory worker living with alcohol dependence, saw me recently at the GP Unit. As we talked about his drinking, I recalled a recent conference presentation on the use of baclofen as a treatment for alcohol use disorders. What is the evidence for this therapy?
What is the effect of baclofen, used as a treatment in people living with alcohol use disorders, on the rate of abstinence.
What does the research evidence say?
Step 1: The Cochrane Library
A protocol for a systematic review on this topic exists in the Cochrane Library, but it has yet to be completed and published.
Step 2: TripDatabase
I conducted a search using the TripDatabase PICO search tool (Participant: “alcohol use disorder”, Intervention: “baclofen”, Comparator: “placebo”, Outcomes: “abstinence”). This identified another yet-to-be-published systematic review underway, published in the PROSPERO register from the University of York Centre of Reviews and Dissemination. I limited the search results to primary research only, which identified 8 randomised trials. None of the published randomised trials can be considered definitive. The paper by Garbutt et al. (2010) published in the journal, “Alcoholism, clinical and experimental research”  was designated as being estimated at low risk of bias by TripDatabase, and in a population without significant comorbidity (relevant to Jorge). I’ll look at this paper in detail, and will briefly cover some of the other studies in the discussion.
I will use the randomised controlled trial appraisal sheet from the Centre for Evidence Based Medicine .
Participants: who was studied?
80 adults from the USA, aged 18-60 recruited through newspaper and radio advertisements, meeting DSM-IV criteria for current alcohol dependence, with at least 2 heavy drinking days per week on average during the 4 weeks prior to screening. Important exclusions: clinically significant medical disease (e.g., cirrhosis) and psychiatric illness (e.g., psychosis), positive urine toxicology, and pregnant women.
Out of 121 participants screened, 80 were randomised, and 61 competed the study. The mean age of the participants was about 50 years, with approximately 25 years of alcohol use. The mean number of (US) standard drinks per day was 7 (approx. 10 Australian standard drinks).
Intervention: what was the exposure?
baclofen 10 mg, three-times-a-day, over 12 weeks, with 8 sessions of a low-intensity psychosocial intervention
Comparator: what was the control/alternative?
placebo tablets, but otherwise the same as the intervention group
Outcomes: what was measured?
Primary outcome: the percentage of heavy drinking days, and percentage of abstinence
Internal validity: are the trial results valid?
Randomised patient assignment?
Yes. The randomisation process was computer generated, and stratified by gender.
Groups similar at the start?
Mostly. The groups were largely similar (see Table 1 from the paper) .
Groups treated equally apart from assigned treatment?
All patients accounted for?
No. Almost a quarter (24%) of the participants did not complete the study. The analysis was conducted on an intention-to-treat basis (see Stat Facts).
Measures objective? Or patients and clinicians kept blinded?
Yes/Probably. There was some validation of patient reported drinking behaviours with the use of breathalysers. The study appeared to have been double-blinded, though the effectiveness of blinding was not reported.
What were the results?
Primary outcomes (baclofen vs placebo):
- No meaningful difference in the average percentage of heavy drinking days:
- 25.9% vs 25.5%, p = 0.56
- No meaningful difference in the average percentage of abstinent days:
- 49.9% vs 50.6%, p = 0.50
- No statistically significant differences were found between groups for craving or depression.
- The baclofen group did have lower levels of anxiety severity.
Discussion and conclusion
Almost a quarter of participants dropped out of this study, which is usually considered significant. This might not affect the overall conclusion, however, as the direction of bias would be towards exaggerating the beneficial effect of baclofen. In this study, baclofen was not statistically or clinically superior to placebo on either the proportion of heavy drinking days, or abstinent days over 3 months.
Earlier case reports and open labelled studies have suggested that baclofen might be an effective treatment for alcohol use disorders. Data from randomised trials have varied. Most of the studies have been small, of short duration, in cohorts with significant comorbidity (e.g., cirrhosis), and some potentially problematic outcome measures.
In my assessment of all the randomised trials that I could identify, those that reported benefit from baclofen [3-7] have tended to be very small (all less than 100 participants), less recent and possibly at higher risk of bias. The trials that did not find a benefit of baclofen over placebo [1, 8, 9] were more recent, and possibly at lower risk of bias. Notably, the largest study (180 participants) in a US Veteran Affairs population with comorbid chronic HCV published this year did not find a beneficial effect with baclofen.
The empirical evidence does not support the use of baclofen as a routine treatment for alcohol use disorders. This was not a treatment I recommended to Jorge.
In randomised trials, noncompliance (to the study protocol) and missing outcomes (e.g., participant drop outs) can lead to exaggerated estimates of treatment effects. One way to address this is for the data to be analysed according to the “intention-to-treat” principle – to include all participants who were randomised in the study .
- Garbutt JC, Kampov-Polevoy AB, Gallop R, Kalka-Juhl L, Flannery BA. Efficacy and safety of baclofen for alcohol dependence: a randomized, double-blind, placebo-controlled trial. Alcohol Clin Exp Res 2010 Nov;34(11):1849-57.
- Centre for Evidence-Based Medicine. Critical Appraisal tools. 2014 [cited 2017 Oct 13]; Available from: http://www.cebm.net/critical-appraisal/
- Addolorato G, Caputo F, Capristo E, et al. Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol and alcoholism 2002 Sep-Oct;37(5):504-8.
- Addolorato G, Leggio L, Ferrulli A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet 2007 Dec 08;370(9603):1915-22.
- Leggio L, Ferrulli A, Zambon A, et al. Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection. Addictive behaviors 2012 Apr;37(4):561-4.
- Morley KC, Baillie A, Leung S, Addolorato G, Leggio L, Haber PS. Baclofen for the Treatment of Alcohol Dependence and Possible Role of Comorbid Anxiety. Alcohol and alcoholism 2014 Nov;49(6):654-60.
- Leggio L, Zywiak WH, Edwards SM, Tidey JW, Swift RM, Kenna GA. A preliminary double-blind, placebo-controlled randomized study of baclofen effects in alcoholic smokers. Psychopharmacology (Berl) 2015 Jan;232(1):233-43.
- Ponizovsky AM, Rosca P, Aronovich E, Weizman A, Grinshpoon A. Baclofen as add-on to standard psychosocial treatment for alcohol dependence: a randomized, double-blind, placebo-controlled trial with 1 year follow-up. J Subst Abuse Treat 2015 May;52:24-30.
- Hauser P, Fuller B, Ho SB, Thuras P, Kern S, Dieperink E. The safety and efficacy of baclofen to reduce alcohol use in veterans with chronic hepatitis C: a randomized controlled trial. Addiction 2017 Jul;112(7):1173-83.
- Gupta SK. Intention-to-treat concept: A review. Perspect Clin Res 2011 Jul;2(3):109-12.