Efficacy and tolerability of baclofen in a U.S. community population with alcohol use disorder: a dose-response, randomized, controlled trial.
Efficacy and tolerability of baclofen in a U.S. community population with alcohol use disorder: a dose-response, randomized, controlled trial.
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DOI：
10.1038/s41386-021-01055-w
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Gallop RJ
中科院分区：
文献类型：
--
作者：
Garbutt JC;Kampov-Polevoy AB;Pedersen C;Stansbury M;Jordan R;Willing L;Gallop RJ
识别酒精使用障碍（AUD）的新药对于改善治疗选择非常重要。巴氯芬是一种GABAB激动剂，已被确定为治疗AUD的潜在药物。在一项为期16周的双盲、随机、安慰剂对照试验中，我们研究了30和90 mg/天的巴氯芬与安慰剂的比较，并检查了剂量、性别和治疗前饮酒水平的影响。120例DSM-IV酒精依赖受试者（年龄46.1（sd = 10.1）岁，51.7%为男性）因不稳定的医学/精神疾病和/或尼古丁以外的药物依赖而被排除后随机分组。73名参与者完成了试验。巴氯芬的主效应为[%HDD（F（2，112）= 4.16，p = 0.018，d = 0.51 95%CI（0.06-0.95），HDD减少13.6）和%ABST（F（2，112）= 3.68，p = 0.028，d = 0.49 95%CI（0.04-0.93），禁欲天数增加12.9）]，并由90 mg/天剂量驱动。%HDD（F（2，110）= 5.48，p = 0.005）和%ABST（F（2，110）= 3.19，p = 0.045）均存在性别×剂量相互作用效应。与PBO相比，90 mg/天的男性显示出轻微的积极作用（%HDD t（110）= 1.88，p = 0.063，d = 0.36 95%CI（−0.09-0.80），HDD天数减少15.8天; %ABST t（110）= 1.68（p = 0.096，d = 0.32 95%CI（−0.12-0.76），ABST增加15.7天），30 mg/天无影响。女性在30毫克/天的剂量下表现出积极的效果（%HDD，t（110）= 3.19，p = 0.002，d = 0.61 95%CI（0.16-1.05），HDD日数减少26.3; %ABST t（110）= 2.73，p = 0.007，d = 0.52 95%CI（0.07-0.96），多25.4个ABST天），90 mg/天对%ABST的边际效应（p = 0.06），90 mg/天剂量组女性因镇静剂副作用而脱落/剂量减少的比例为59%，男性为5%。这些发现支持了巴氯芬对AUD有效的假设，并表明剂量和性别作为巴氯芬反应和耐受性的潜在调节因素需要进一步研究。
Identification of new medications for alcohol use disorder (AUD) is important for improving treatment options. Baclofen, a GABAB agonist, has been identified as a potential pharmacotherapy for AUD. In a 16-week double-blind, randomized, placebo-controlled trial, we investigated 30 and 90 mg/day of baclofen compared to placebo and examined effects of dose, sex, and level of pretreatment drinking. One hundred and twenty participants with DSM-IV alcohol dependence (age 46.1 (sd = 10.1) years, 51.7% male) were randomized after exclusion for unstable medical/psychiatric illness and/or dependence on drugs other than nicotine. Seventy-three participants completed the trial. A main effect of baclofen was found [%HDD (F(2,112) = 4.16, p = 0.018, d = 0.51 95%CI (0.06–0.95), 13.6 fewer HDD) and %ABST (F(2,112) = 3.68, p = 0.028, d = 0.49 95%CI (0.04–0.93), 12.9 more abstinent days)] and was driven by the 90 mg/day dose. A sex × dose interaction effect was present for both %HDD (F(2,110) = 5.48, p = 0.005) and %ABST (F(2,110) = 3.19, p = 0.045). Men showed a marginally positive effect for 90 mg/day compared to PBO (%HDD t(110) = 1.88, p = 0.063, d = 0.36 95%CI (−0.09–0.80), 15.8 fewer HDD days; %ABST t(110) = 1.68 (p = 0.096, d = 0.32 95%CI (−0.12–0.76), 15.7 more ABST)) with no effect for 30 mg/day. Women showed a positive effect for 30 mg/day (%HDD, t(110) = 3.19, p = 0.002, d = 0.61 95%CI (0.16–1.05), 26.3 fewer HDD days; %ABST t(110) = 2.73, p = 0.007, d = 0.52 95%CI (0.07–0.96), 25.4 more ABST days) with marginal effects for 90 mg/day on %ABST (p = 0.06) with drop-outs/dose reduction from sedative side-effects of 59% in women at 90 mg/day compared to 5% for men. These findings support the hypothesis that baclofen has efficacy in AUD and suggest that dose and sex be further explored as potential moderators of baclofen response and tolerability.
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