From the Addiction Sciences Division, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC.
J Addict Med. 2024;18(5):520-525. doi: 10.1097/ADM.0000000000001316. Epub 2024 May 31.
Alcohol consumption affects sleep both in healthy populations and in patients with alcohol use disorder (AUD). However, sleep has typically not been considered within AUD pharmacotherapy trials. We used data from a completed gabapentin clinical treatment trial to explore the medication's effect on patient-rated insomnia measured by a standard insomnia rating (Insomnia Severity Index [ISI]) and whether this influenced gabapentin's effects on alcohol consumption.
This study included 90 individuals with current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition AUD criteria reporting current or past alcohol withdrawal. Participants were assigned to placebo or gabapentin (up to 1200 mg/day) for a 16-week randomized controlled trial with percent heavy drinking days (PHDD) and percent abstinent days (PDA) as outcomes. Utilizing mixed-effects models, this study assessed medication effects on ISI over the trial. We then examined the interaction of baseline ISI and medication on drinking. Finally, given our previous finding of alcohol withdrawal influencing gabapentin efficacy, we added change in ISI as a potential "moderator" of the interaction of medication effects and alcohol withdrawal on drinking.
Sleep (ISI) improved more in those treated with gabapentin (60.6% reduction) compared with placebo (37.8% reduction; P = 0.013). Higher baseline ISI predicted drinking in gabapentin-treated individuals (lower PHDD [ P = 0.026] and higher (PDA [ P = 0.047]). ISI was an independent predictor of PHDD decrease and PDA increase ( P < 0.001; P = 0.002), but this did not significantly moderate gabapentin's effectiveness.
Although gabapentin positively impacts both alcohol use and sleep, its effect on drinking is not fully dependent on sleep improvement, implying a direct biological mechanism on alcohol use.
饮酒在健康人群和酒精使用障碍(AUD)患者中均会影响睡眠。然而,睡眠通常未被纳入 AUD 药物治疗试验中。我们使用已完成的加巴喷丁临床治疗试验的数据,来探讨该药物对患者自评失眠的影响,使用的评估工具为标准失眠评估量表(ISI),并探讨这是否会影响加巴喷丁对饮酒的影响。
本研究纳入了 90 名符合《精神障碍诊断与统计手册》第五版 AUD 标准的个体,这些个体报告目前或过去存在酒精戒断。参与者被随机分配至安慰剂或加巴喷丁(最高 1200mg/天)组,进行为期 16 周的随机对照试验,以重度饮酒天数(PHDD)和无饮酒天数(PDA)作为结局指标。本研究使用混合效应模型评估试验过程中 ISI 的药物效应。我们随后检查了 ISI 基线值和药物治疗的交互作用对饮酒的影响。最后,鉴于我们之前发现酒精戒断会影响加巴喷丁的疗效,我们将 ISI 的变化作为药物治疗效果和酒精戒断对饮酒影响的交互作用的潜在“调节剂”纳入分析。
与安慰剂组(ISI 降低 37.8%)相比,加巴喷丁组的睡眠(ISI)改善更明显(ISI 降低 60.6%;P = 0.013)。较高的基线 ISI 预示着加巴喷丁治疗个体的饮酒增加(较低的 PHDD[P = 0.026]和较高的 PDA[P = 0.047])。ISI 是 PHDD 减少和 PDA 增加的独立预测因子(P < 0.001;P = 0.002),但这并未显著调节加巴喷丁的疗效。
尽管加巴喷丁对饮酒和睡眠均有积极影响,但它对饮酒的影响并非完全依赖于睡眠改善,这暗示了其对饮酒的影响存在直接的生物学机制。