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. 2023 Jan 13;1(1):CD012557.
doi: 10.1002/14651858.CD012557.pub3.

Baclofen for alcohol use disorder

Roberta Agabio  1 , Rosella Saulle  2 , Susanne Rösner  3 , Silvia Minozzi  2
Affiliations

Baclofen for alcohol use disorder

Roberta Agabio et al. Cochrane Database Syst Rev. .

Abstract

Background: Alcohol use disorder (AUD) is one of the most widespread psychiatric disorders leading to detrimental consequences to people with this disorder and others. Worldwide, the prevalence of heavy episodic drinking (30-day prevalence of at least one occasion of 60 g of pure alcohol intake among current drinkers) is estimated at 20% and the prevalence of AUD at 5% of the adult general population, with highest prevalence in Europe and North America. Therapeutic approaches, including pharmacotherapy, play an important role in treating people with AUD. This is an update of a Cochrane Review first published in 2018.

Objectives: To evaluate the benefits and harms of baclofen on achieving and maintaining abstinence or reducing alcohol consumption in people with AUD compared to placebo, no treatment or any other pharmacological relapse prevention treatment.

Search methods: We used standard, extensive Cochrane search methods. The latest search was 22 November 2021.

Selection criteria: Randomised controlled trials (RCTs) of at least four weeks' treatment duration and 12 weeks' overall study duration comparing baclofen for AUD treatment with placebo, no treatment or other treatments.

Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were 1. relapse, 2. frequency of use, 3. amount of use, 4. adverse events, 5. dropouts from treatment and 6. dropouts from treatment due to adverse events. Our secondary outcomes were 7. craving, 8. anxiety, 9. depression and 10. frequency of most relevant adverse events.

Main results: We included 17 RCTs (1818 participants) with a diagnosis of alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition or International Classification of Diseases 10th edition criteria. Mean age was 46.5 years and 70% were men. Ten studies compared baclofen to placebo or another medication; seven compared two baclofen doses to placebo or another medication. Globally, 15 studies compared baclofen to placebo, two baclofen to acamprosate and two baclofen to naltrexone. In 16 studies, participants received psychosocial treatments. We judged most studies at low risk of selection, performance, detection (subjective outcome), attrition and reporting bias. Ten studies detoxified participants before treatment; in seven studies, participants were still drinking at the beginning of treatment. Treatment duration was 12 weeks for 15 RCTs and longer in two studies. Baclofen daily dose was 30 mg to 300 mg: 10 RCTs used low doses (30 mg or less); eight RCTs medium doses (above 30 and 100 mg or less) and four RCTs high doses (above 100 mg). Compared to placebo, moderate-certainty evidence found that baclofen probably decreases the risk to relapse (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.77 to 0.99; 12 studies, 1057 participants). This result was confirmed among detoxified participants but not among other subgroups of participants. High-certainty evidence found that baclofen increases the percentage of days abstinent (mean difference (MD) 9.07, 95% CI 3.30 to 14.85; 16 studies, 1273 participants). This result was confirmed among all subgroups of participants except non-detoxified or those who received medium doses. There was no difference between baclofen and placebo in the other primary outcomes: heavy drinking days (standardised mean difference (SMD) -0.18, 95% CI -0.48 to 0.11; 13 studies, 840 participants; moderate-certainty evidence); number of drinks per drinking days (MD -0.45, 95% CI -1.20 to 0.30; 9 studies, 392 participants; moderate-certainty evidence); number of participants with at least one adverse event (RR 1.05, 95% CI 0.99 to 1.11; 10 studies, 738 participants; high-certainty evidence); dropouts (RR 0.88, 95% CI 0.74 to 1.03; 17 studies, 1563 participants; high-certainty evidence); dropouts due to adverse events (RR 1.39, 95% CI 0.89 to 2.18; 16 studies, 1499 participants; high-certainty evidence). These results were confirmed by subgroup analyses except than for the dropouts that resulted lower among participants who received high doses of baclofen and studies longer than 12 weeks. Compared to placebo, there was no difference in craving (SMD -0.16, 95% CI -0.37 to 0.04; 17 studies, 1275 participants), anxiety (MD -0.01, 95% CI -0.14 to 0.11; 15 studies, 1123 participants) and depression (SMD 0.07, 95% CI -0.12 to 0.27; 11 studies, 1029 participants). Concerning the specific adverse events, baclofen increases fatigue, dizziness, somnolence/sedation, dry mouth, paraesthesia and muscle spasms/rigidity. There was no difference in the other adverse events. Compared to acamprosate, one study (60 participants) found no differences in any outcomes but the evidence was very uncertain: relapse (RR 1.25, 95% CI 0.71 to 2.20; very low-certainty evidence); number of participants with at least one adverse event (RR 0.63, 95% CI 0.23 to 1.69; very low-certainty evidence); dropouts (RR 0.56, 95% CI 0.21 to 1.46; very low-certainty evidence); dropouts due to adverse events (RR 0.33, 95% CI 0.01 to 7.87; very low-certainty evidence) and craving (MD 5.80, 95% CI -11.84 to 23.44); and all the adverse events evaluated. Compared to naltrexone, baclofen may increase the risk of relapse (RR 2.50, 95% CI 1.12 to 5.56; 1 study, 60 participants; very low-certainty evidence) and decrease the number of participants with at least one adverse event (RR 0.35, 95% CI 0.15 to 0.80; 2 studies, 80 participants; very low-certainty evidence) but the evidence is very uncertain. One study (60 participants) found no difference between baclofen and naltrexone in the dropouts at the end of treatment (RR 1.00, 95% CI 0.32 to 3.10; very low-certainty evidence), craving (MD 2.08, 95% CI -3.71 to 7.87), and all the adverse events evaluated.

Authors' conclusions: Baclofen likely reduces the risk of relapse to any drinking and increases the percentage of abstinent days, mainly among detoxified participants. It does not increase the number of participants with at least one adverse event, those who dropout for any reason or due to adverse events. It probably does not reduce number of heavy drinking days and the number of drinks per drinking days. Current evidence suggests that baclofen may help people with AUD in maintaining abstinence. The results of comparisons of baclofen with acamprosate and naltrexone were mainly based on only one study.

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Conflict of interest statement

RA: none.

RS: none.

SR: none.

SM: none.

Figures

1
1
PRISMA study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
4
4
5
5
6
6
7
7
8
8
1.1
1.1. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 1: Relapse: return to any drinking at end of treatment
1.2
1.2. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 2: Frequency of use: % days abstinence at end of treatment
1.3
1.3. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 3: Frequency of use: heavy drinking days at end of treatment
1.4
1.4. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 4: Amount of use: drinks per drinking days at end of treatment
1.5
1.5. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 5: Adverse events: number of participants with at least one adverse event at end of treatment
1.6
1.6. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 6: Dropouts at end of treatment
1.7
1.7. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 7: Dropouts due to adverse events
1.8
1.8. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 8: Craving
1.9
1.9. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 9: Anxiety
1.10
1.10. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 10: Depression
1.11
1.11. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 11: Adverse events: fatigue, tiredness
1.12
1.12. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 12: Adverse events: insomnia
1.13
1.13. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 13: Adverse events: pain (diverse)
1.14
1.14. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 14: Adverse events: vertigo, dizziness
1.15
1.15. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 15: Adverse events: constipation
1.16
1.16. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 16: Adverse events: somnolence, sleepiness, drowsiness or sedation
1.17
1.17. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 17: Adverse events: muscle pain
1.18
1.18. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 18: Adverse events: dry mouth
1.19
1.19. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 19: Adverse events: nausea
1.20
1.20. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 20: Adverse events: skin rash
1.21
1.21. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 21: Adverse events: headaches
1.22
1.22. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 22: Adverse events: paraesthesia/numbness
1.23
1.23. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 23: Adverse events: diarrhoea
1.24
1.24. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 24: Adverse events: tinnitus
1.25
1.25. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 25: Adverse events: muscle spasm/rigidity
1.26
1.26. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 26: Adverse events: hyperhidrosis
1.27
1.27. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 27: Adverse events: nasopharyngitis
1.28
1.28. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 28: Adverse events: decrease appetite/anorexia
1.29
1.29. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 29: Adverse events: dysgeusia/ageusia
1.30
1.30. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 30: Adverse events: tremor
1.31
1.31. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 31: Adverse events: weakness
1.32
1.32. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 32: Adverse events: vomiting
1.33
1.33. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 33: Adverse events: urinary frequency
1.34
1.34. Analysis
Comparison 1: Baclofen versus placebo (all studies), Outcome 34: Adverse events: shortness of breath
2.1
2.1. Analysis
Comparison 2: Baclofen versus placebo (divided into low, medium and high doses of baclofen), Outcome 1: Relapse: return to any drinking at end of treatment
2.2
2.2. Analysis
Comparison 2: Baclofen versus placebo (divided into low, medium and high doses of baclofen), Outcome 2: Frequency of use: % days abstinence at end of treatment
2.3
2.3. Analysis
Comparison 2: Baclofen versus placebo (divided into low, medium and high doses of baclofen), Outcome 3: Frequency of use: % of heavy drinking days at end of treatment
2.4
2.4. Analysis
Comparison 2: Baclofen versus placebo (divided into low, medium and high doses of baclofen), Outcome 4: Amount of use: drinks per drinking days at end of treatment
2.5
2.5. Analysis
Comparison 2: Baclofen versus placebo (divided into low, medium and high doses of baclofen), Outcome 5: Adverse events: number of participants with at least one adverse event at end of treatment
2.6
2.6. Analysis
Comparison 2: Baclofen versus placebo (divided into low, medium and high doses of baclofen), Outcome 6: Dropouts at end of treatment
2.7
2.7. Analysis
Comparison 2: Baclofen versus placebo (divided into low, medium and high doses of baclofen), Outcome 7: Dropouts due to adverse events
3.1
3.1. Analysis
Comparison 3: Baclofen versus placebo (divided into 12‐week and longer than 12‐week studies), Outcome 1: Relapse: return to any drinking at end of treatment
3.2
3.2. Analysis
Comparison 3: Baclofen versus placebo (divided into 12‐week and longer than 12‐week studies), Outcome 2: Frequency of use: % days abstinence at end of treatment
3.3
3.3. Analysis
Comparison 3: Baclofen versus placebo (divided into 12‐week and longer than 12‐week studies), Outcome 3: Frequency of use: % of heavy drinking days at end of treatment
3.4
3.4. Analysis
Comparison 3: Baclofen versus placebo (divided into 12‐week and longer than 12‐week studies), Outcome 4: Amount of use: drink per drinking days at end of treatment
3.5
3.5. Analysis
Comparison 3: Baclofen versus placebo (divided into 12‐week and longer than 12‐week studies), Outcome 5: Adverse events: number of participants with at least one adverse event at end of treatment
3.6
3.6. Analysis
Comparison 3: Baclofen versus placebo (divided into 12‐week and longer than 12‐week studies), Outcome 6: Dropouts at end of treatment
3.7
3.7. Analysis
Comparison 3: Baclofen versus placebo (divided into 12‐week and longer than 12‐week studies), Outcome 7: Dropout due to adverse events
4.1
4.1. Analysis
Comparison 4: Baclofen versus placebo (divided into detoxified and non‐detoxified participants), Outcome 1: Relapse: return to any drinking at end of treatment
4.2
4.2. Analysis
Comparison 4: Baclofen versus placebo (divided into detoxified and non‐detoxified participants), Outcome 2: Frequency of use: % days abstinence at end of treatment
4.3
4.3. Analysis
Comparison 4: Baclofen versus placebo (divided into detoxified and non‐detoxified participants), Outcome 3: Frequency of use: % of heavy drinking days at end of treatment
4.4
4.4. Analysis
Comparison 4: Baclofen versus placebo (divided into detoxified and non‐detoxified participants), Outcome 4: Amount of use: drink per drinking days at end of treatment
4.5
4.5. Analysis
Comparison 4: Baclofen versus placebo (divided into detoxified and non‐detoxified participants), Outcome 5: Adverse events: number of participants with at least one adverse event at end of treatment
4.6
4.6. Analysis
Comparison 4: Baclofen versus placebo (divided into detoxified and non‐detoxified participants), Outcome 6: Dropouts at end of treatment
4.7
4.7. Analysis
Comparison 4: Baclofen versus placebo (divided into detoxified and non‐detoxified participants), Outcome 7: Dropouts due to adverse events
5.1
5.1. Analysis
Comparison 5: Baclofen versus acamprosate, Outcome 1: Relapse: return to any drinking at end of treatment
5.2
5.2. Analysis
Comparison 5: Baclofen versus acamprosate, Outcome 2: Adverse events: number of participants with at least one adverse event at end of treatment
5.3
5.3. Analysis
Comparison 5: Baclofen versus acamprosate, Outcome 3: Dropouts at end of treatment
5.4
5.4. Analysis
Comparison 5: Baclofen versus acamprosate, Outcome 4: Dropouts due to adverse events
5.5
5.5. Analysis
Comparison 5: Baclofen versus acamprosate, Outcome 5: Craving
5.6
5.6. Analysis
Comparison 5: Baclofen versus acamprosate, Outcome 6: Adverse events: fatigue, tiredness
5.7
5.7. Analysis
Comparison 5: Baclofen versus acamprosate, Outcome 7: Adverse events: vertigo, dizziness
5.8
5.8. Analysis
Comparison 5: Baclofen versus acamprosate, Outcome 8: Adverse events: nausea
5.9
5.9. Analysis
Comparison 5: Baclofen versus acamprosate, Outcome 9: Adverse events: skin rash
5.10
5.10. Analysis
Comparison 5: Baclofen versus acamprosate, Outcome 10: Adverse events: decrease appetite/anorexia
5.11
5.11. Analysis
Comparison 5: Baclofen versus acamprosate, Outcome 11: Adverse events: acidity
5.12
5.12. Analysis
Comparison 5: Baclofen versus acamprosate, Outcome 12: Adverse events: palpitations
6.1
6.1. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 1: Relapse: return to any drinking at end of treatment
6.2
6.2. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 2: Adverse events: number of participants with at least one adverse event at end of treatment
6.3
6.3. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 3: Dropouts at end of treatment
6.4
6.4. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 4: Craving
6.5
6.5. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 5: Adverse events: fatigue, tiredness
6.6
6.6. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 6: Adverse events: insomnia
6.7
6.7. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 7: Adverse events: vertigo, dizziness
6.8
6.8. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 8: Adverse events: somnolence, sleepiness, drowsiness or sedation
6.9
6.9. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 9: Adverse events: nausea
6.10
6.10. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 10: Adverse events: decrease appetite/anorexia
6.11
6.11. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 11: Adverse events: tremor
6.12
6.12. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 12: Adverse events: acidity
6.13
6.13. Analysis
Comparison 6: Baclofen versus naltrexone, Outcome 13: Adverse events: erectile dysfunction
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References

References to studies included in this review

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Morley 2018‐MD {published and unpublished data}
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Muller 2015 {published data only}
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Rigal 2020 {published and unpublished data}
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References to studies excluded from this review

Addolorato 2002 {published data only}
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Flannery 2004 {published data only}
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Gupta 2017 {published data only}
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Jose 2019 {published data only}
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Kumar 2020b {published data only}
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Leggio 2013 {published data only}
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References to studies awaiting assessment

Karthik 2018 {published data only}
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Sharma 2012 {published data only}
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References to ongoing studies

CTRI/2011/11/002154 {published data only}
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