Kotake Kazumasa, So Ryuhei, Hashimoto Nozomu, Imai Eriya, Kaneko Takao, Banno Masahiro, Furukawa Yuki
Department of Pharmacy, Zikei Hospital/Zikei Institute of Psychiatry, 100-2 Urayasu Honmachi, Minami-Ku, Okayama-shi, Okayama, 702-8508, Japan.
Scientific Research WorkS Peer Support Group (SRWS-PSG), Osaka, Japan.
CNS Drugs. 2025 May 10. doi: 10.1007/s40263-025-01188-2.
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.
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.
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.
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.
巴氯芬是一种治疗痉挛的传统药物，目前其在酒精使用障碍（AUD）治疗中的应用正受到越来越多的关注。为帮助临床医生有效且安全地使用巴氯芬治疗AUD，我们通过系统评价和剂量反应荟萃分析对巴氯芬的最佳目标剂量进行了研究。
我们于2024年4月1日和2日在Cochrane图书馆、EMBASE、通过PubMed检索的MEDLINE、PsycINFO、ClinicalTrials.gov以及国际临床试验注册平台上搜索关于随机对照试验的文献。纳入标准为年龄≥18岁、根据《精神疾病诊断与统计手册》（DSM）-IV、DSM-IV-TR或《国际疾病分类》（ICD）-10诊断为AUD且接受巴氯芬单一疗法治疗的患者。连续型结局指标——戒酒天数百分比、每日饮酒量、重度饮酒天数（HDDs）、渴望程度和焦虑水平——以均值或标准化均值差进行分析。二分类结局指标——复发和脱落（包括因不良事件导致的脱落）——以比值比进行分析。每个结局指标均使用Cochrane偏倚风险2.0工具进行评估。采用限制立方样条法进行单阶段随机效应剂量反应荟萃分析，固定节点位于第10、50和90百分位数处。
共纳入14项试验（1344例患者）。将巴氯芬剂量增至50 - 60毫克/天与更高的戒酒天数百分比及更低的渴望程度相关。然而，更高剂量的巴氯芬会增加因不良事件导致脱落的风险。常见的不良事件有嗜睡、镇静、昏睡和疲劳。剂量达50 - 60毫克/天的巴氯芬对每日饮酒量、HDDs、焦虑、复发或脱落无显著影响。由于数据有限和研究异质性，剂量>60毫克/天缺乏可靠评估。
剂量达50 - 60毫克/天的巴氯芬可能会增加戒酒天数百分比并降低渴望程度，但可能会因不良事件增加脱落率。临床医生在为AUD患者开具巴氯芬处方时应仔细考虑个体患者因素。
