Addiction Sciences Division, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston.
JAMA Intern Med. 2020 May 1;180(5):728-736. doi: 10.1001/jamainternmed.2020.0249.
Although an estimated 30 million people meet criteria for alcohol use disorder (AUD), few receive appropriate pharmacotherapy. A more personalized, symptom-specific, approach might improve efficacy and acceptance.
To examine whether gabapentin would be useful in the treatment of AUD, especially in those with the most alcohol withdrawal symptoms.
DESIGN, SETTING, AND PARTICIPANTS: This double-blind randomized clinical trial conducted between November 2014 and June 2018 evaluated gabapentin vs placebo in community-recruited participants screened and treated in an academic outpatient setting over a 16-week treatment period. A total of 145 treatment-seeking individuals who met Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for AUD and were not receiving other AUD intervention were screened, and 96 who also met recent alcohol withdrawal criteria were randomized to treatment after 3 abstinent days. Daily drinking was recorded, and percentage of disialo carbohydrate-deficient transferrin in the blood, a heavy drinking marker, was collected at baseline and monthly during treatment.
Gabapentin up to 1200 mg/d, orally, vs placebo along with 9 medical management visits (20 minutes each).
The percentage of individuals with no heavy drinking days and those with total abstinence were compared between treatment groups and further evaluated based on prestudy alcohol withdrawal symptoms.
Of 96 randomized individuals, 90 were evaluable (44 in the gabapentin arm and 46 in the placebo arm), with a mean (SD) age of 49.6 (10.1) years; 69 were men (77%) and 85 were white (94%). The evaluable participants had 83% baseline heavy drinking days (4 or more drinks/day for women, 5 or more for men) and met 4.5 alcohol withdrawal criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). More gabapentin-treated individuals had no heavy drinking days (12 of 44 participants [27%]) compared with placebo (4 of 46 participants [9%]), a difference of 18.6% (95% CI, 3.1-34.1; P = .02; number needed to treat [NNT], 5.4), and more total abstinence (8 of 44 [18%]) compared with placebo (2 of 46 [4%]), a difference of 13.8% (95% CI, 1.0-26.7; P = .04; NNT, 6.2). The prestudy high-alcohol withdrawal group had positive gabapentin effects on no heavy drinking days (P < .02; NNT, 3.1) and total abstinence (P = .003; NNT, 2.7) compared with placebo, while within the low-alcohol withdrawal group, there were no significant differences. These findings were similar for other drinking variables, where gabapentin was more efficacious than placebo in the high-alcohol withdrawal group only. Gabapentin caused more dizziness, but this did not affect efficacy.
These data, combined with others, suggest gabapentin might be most efficacious in people with AUD and a history of alcohol withdrawal symptoms. Future studies should evaluate sleep changes and mood during early recovery as mediators of gabapentin efficacy.
ClinicalTrials.gov Identifier: NCT02349477.
尽管约有 3000 万人符合酒精使用障碍（AUD）的标准，但很少有人接受适当的药物治疗。更个性化、症状特异性的方法可能会提高疗效和接受度。
研究加巴喷丁是否对 AUD 治疗有用，尤其是对那些酒精戒断症状最严重的患者。
设计、地点和参与者：这项双盲随机临床试验于 2014 年 11 月至 2018 年 6 月进行，在学术门诊环境中招募和治疗社区招募的参与者，评估加巴喷丁与安慰剂在 16 周治疗期间的疗效。共筛选了 145 名符合《精神障碍诊断与统计手册》（第五版）酒精使用障碍标准且未接受其他 AUD 干预的治疗寻求者，并随机分配了 96 名近期酒精戒断标准的患者在 3 天禁欲后接受治疗。记录每日饮酒量，并在基线和治疗期间每月采集血液中双唾液酸神经节苷脂缺乏转移蛋白的百分比，这是一个衡量大量饮酒的标志物。
加巴喷丁最高剂量为 1200mg/d，口服，与安慰剂一起使用，共 9 次医疗管理就诊（每次 20 分钟）。
比较两组治疗后无大量饮酒天数和完全戒断的患者比例，并根据研究前的酒精戒断症状进行进一步评估。
在随机的 96 名参与者中，有 90 名可评估（加巴喷丁组 44 名，安慰剂组 46 名），平均（SD）年龄为 49.6（10.1）岁；69 名参与者为男性（77%），85 名参与者为白人（94%）。可评估的参与者基线时大量饮酒天数占 83%（女性 4 天或以上，男性 5 天或以上），符合《精神障碍诊断与统计手册》（第五版）中 4.5 项酒精戒断标准。与安慰剂组（4 名参与者[9%]）相比，加巴喷丁组有更多的参与者无大量饮酒天数（44 名参与者中的 12 名[27%]），差异为 18.6%（95%CI，3.1-34.1；P=0.02；需要治疗的人数[NNT]，5.4），加巴喷丁组完全戒断的参与者也多于安慰剂组（44 名参与者中的 8 名[18%]），差异为 13.8%（95%CI，1.0-26.7；P=0.04；NNT，6.2）。在研究前高酒精戒断组中，与安慰剂相比，加巴喷丁对无大量饮酒天数（P<0.02；NNT，3.1）和完全戒断（P=0.003；NNT，2.7）的疗效更显著，而在低酒精戒断组中，加巴喷丁与安慰剂之间没有显著差异。这些发现与其他饮酒变量相似，加巴喷丁在高酒精戒断组的疗效优于安慰剂。加巴喷丁引起更多的头晕，但这并不影响疗效。
这些数据与其他数据相结合，表明加巴喷丁在有 AUD 和酒精戒断症状史的人群中可能最有效。未来的研究应该评估早期康复期间的睡眠变化和情绪作为加巴喷丁疗效的中介。
ClinicalTrials.gov 标识符：NCT02349477。
