Objective:

Although gabapentin has demonstrated efficacy in mitigating alcohol withdrawal symptoms and preventing relapse drinking in individuals with alcohol use disorder (AUD), the neurobiological mechanisms of action underlying these therapeutic effects remain unknown. The present study evaluated changes in GABA and glutamate levels in the dorsal anterior cingulate cortex (dACC) as candidate mechanisms of action.

Methods:

In a 16-week randomized clinical trial, 68 adults with AUD, including a history of alcohol withdrawal syndrome, received 1,200 mg/day of gabapentin (N=37) or placebo (N=31) and nine medical management visits after ≥72 hours of abstinence. Proton MR spectroscopy (¹H-MRS) estimates of dACC levels of GABA (N=67) and glutamate (N=64) were acquired before start of treatment and again approximately 14 days after randomization. Percent days abstinent was reported via timeline followback interview.

Results:

The effects of gabapentin on GABA and glutamate levels were significantly associated with participants’ percent days abstinent during early treatment. Specifically, gabapentin was associated with greater increases in glutamate and greater decreases in GABA levels in participants who remained mostly or entirely abstinent, and yet the opposite in participants who drank on more than half of the days preceding the second scan. Furthermore, gabapentin-treated participants with greater increases in glutamate levels during early treatment had significantly more percent days abstinent across the remainder of the study, relative to placebo-treated participants.

Conclusions:

In addition to providing insight into the mechanisms through which gabapentin may promote abstinence in individuals with AUD, this study also provides evidence for a biomarker of efficacious treatment that may be used to evaluate other glutamatergic or GABAergic medications for AUD and related conditions.

中文翻译：

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加巴喷丁对背侧前扣带回 GABA 和谷氨酸水平的影响及其与戒酒在酒精使用障碍中的关系：一项随机临床试验

客观的：

尽管加巴喷丁已证明在减轻酒精戒断症状和预防酒精使用障碍 (AUD) 患者复发饮酒方面的功效，但这些治疗效果背后的神经生物学作用机制仍然未知。本研究评估了背侧前扣带皮层 (dACC) 中 GABA 和谷氨酸水平的变化作为候选的作用机制。

方法：

在一项为期 16 周的随机临床试验中，68 名患有 AUD 的成年人（包括有酒精戒断综合征病史）接受了 1,200 毫克/天的加巴喷丁（N=37）或安慰剂（N=31），并在≥72 小时后接受了 9 次医疗管理访问的禁欲。在治疗开始前和随机化后约 14 天再次获得 GABA (N=67) 和谷氨酸 (N=64) 的 dACC 水平的质子 MR 光谱 ( ^{1 H-MRS) 估计值。}通过时间线跟进采访报告了戒酒的百分比。

结果：

加巴喷丁对 GABA 和谷氨酸水平的影响与参与者在早期治疗期间的戒断天数显着相关。具体而言，加巴喷丁与大部分或完全戒酒的参与者的谷氨酸增加更多和 GABA 水平的减少有关，而在第二次扫描前一半以上的时间里饮酒的参与者则相反。此外，与安慰剂治疗的参与者相比，在早期治疗期间谷氨酸水平增加较多的加巴喷丁治疗参与者在研究的其余部分中的禁欲天数显着增加。

结论：

除了深入了解加巴喷丁可能促进 AUD 患者戒断的机制外，本研究还为有效治疗的生物标志物提供了证据，该生物标志物可用于评估其他谷氨酸能或 GABA 能药物治疗 AUD 和相关疾病。