Optimal Dose of Baclofen for the Treatment of Alcohol Use Disorder: A Systematic Review and Dose-Response Meta-analysis.

Background and objectives

Baclofen, a traditional treatment for spasticity, is gaining interest for its use in alcohol use disorder (AUD). To assist clinicians in using baclofen for effective and safe treatment of AUD, we investigated the optimal target dosage of baclofen through a systematic review and dose-response meta-analysis.

Methods

We searched Cochrane, EMBASE, MEDLINE via PubMed, PsycINFO, ClinicalTrials.gov, and the International Clinical Trials Registry Platform for randomized controlled trials on 1 and 2 April 2024. Inclusion criteria were patients aged ≥ 18 years diagnosed with AUD according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, DSM-IV-TR, or International Classification of Diseases (ICD)-10, and treated with baclofen monotherapy. Continuous outcomes-percent days abstinent, drinks per drinking day, heavy drinking days (HDDs), craving, and anxiety-were analyzed as mean or standardized mean differences. Binary outcomes-relapse and dropout, including due to adverse events-were analyzed as odds ratios. Each outcome was assessed using the Cochrane Risk of Bias 2.0 tool. A one-stage random-effects dose-response meta-analysis was performed using restricted cubic splines with fixed knots at 10%, 50%, and 90% percentiles.

Results

A total of 14 trials (1344 patients) were included. Increasing the dose of baclofen up to 50-60 mg/day was associated with a higher percent days abstinent and reduced craving. However, a higher baclofen dose increases the risk of dropout due to adverse events. Commonly observed adverse events were drowsiness, sedation, somnolence and fatigue. Baclofen up to 50-60 mg/day did not significantly affect drinks per drinking day, HDDs, anxiety, relapse or dropout. Doses > 60 mg/day lacked reliable evaluation due to limited data and study heterogeneity.

Conclusions

Baclofen up to 50-60 mg/day may increase percent days abstinent and reduce craving, but may increase dropout due to adverse events. Clinicians should carefully consider individual patient factors when prescribing baclofen to patients with AUD.

COI Statement

Declarations. Competing Interests: K.K. has received speaker honoraria from Asahi Kasei Pharma Co., Ltd. R.S. has received research grants from the Osake-no-Kagaku Foundation and speaker honoraria from Otsuka Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Sumitomo Pharma Co., Ltd., and Takeda Pharmaceutical Co., Ltd. outside the submitted work. R.S. also reports employment at CureApp Inc., which has developed software as a medical device for AUD. In addition, RS holds pending patents: JP2022049590 A, US20220084673 A1, JP2022178215 A, JP2022070086, and JP2023074128 A. N.H. has received honoraria for speaking at educational events sponsored by Otsuka Pharmaceutical Co., Ltd., Viatris, and Takeda Pharmaceutical Co., Ltd. Y.F. has received consultancy fees from Panasonic and lecture fees from Otsuka Pharmaceutical Co., Ltd., outside the submitted work. The other authors have no conflicts of interest to declare. Funding: No funding. Data Availability: Data supporting the findings of this study are available at Open Science Framework ( https://osf.io/k3ca2/ ). Further data are available from the corresponding author upon reasonable request (kottanketty@gmail.com). Ethics Approval: Systematic reviews and dose-response meta-analyses do not require ethical approval because they use publicly accessible documents as evidence. Consent to Participate: Systematic reviews and dose-response meta-analyses use publicly accessible documents as evidence; therefore, there is no need to seek consent to participate. Consent to Publish: Systematic reviews and dose-response meta-analyses use publicly accessible documents as evidence; therefore, there consent for publication is not required. Code Availability: This codec is available in the Open Science Framework ( https://osf.io/k3ca2/ ). Additional data are available from the corresponding author upon request (kottanketty@gmail.com). Author Contributions: Conception and design of the study: K.K. Acquisition and analysis of data: K.K., E.I., T.K., and Y.F. Drafting the manuscript or figures: K.K. Critical revision of the manuscript: R.S., N.H., M.B., and Y.F. Supervision: R.S., M.B. and Y.F. All the authors have read and approved the final manuscript and agree to be accountable for the work.

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