Winterlind Emma L, Malone Samantha G, Setzer Michael R, Murphy Mikela A, Saunders David, Gray Joshua C
Uniformed Services University of the Health Sciences, Department of Medical and Clinical Psychology, Bethesda, MD, 20814.
Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817.
medRxiv. 2024 Aug 26:2024.05.13.24306839. doi: 10.1101/2024.05.13.24306839.
N-acetylcysteine (NAC) may serve as a novel pharmacotherapy for substance use and substance craving in individuals with substance use disorders (SUDs), possibly through its potential to regulate glutamate. Though prior meta-analyses generally support NAC's efficacy in reducing symptoms of craving, individual trials have found mixed results. The aims of the this updated meta-analysis were to (1) examine the efficacy of NAC in treating symptoms of craving in individuals with a SUD and (2) explore subgroup differences, risk of bias, and publication bias across trials. Database searches of PubMed, Cochrane Library, and ClinicalTrials.gov were conducted in June and July of 2023 to identify relevant randomized control trials (RCTs). The meta-analysis consisted of 9 trials which analyzed data from a total of 623 participants. The most targeted substance in the clinical trials was alcohol (3/9; 33.3%), followed by tobacco (2/9; 22.2%) and multiple substances (2/9; 22.2%). Meta-analysis, subgroup analyses, and leave-one-out analyses were conducted to examine treatment effect on craving symptoms and adverse events (AEs). Risk of bias assessments, Egger's tests, and funnel plot tests were conducted to examine risk of bias and publication bias. NAC did not significantly outperform placebo in reducing symptoms of craving in the meta-analysis (SMD = 0.189, 95% CI = -0.015 - 0.393). Heterogeneity was very high in the meta-analysis (99.26%), indicating that findings may have been influenced by clinical or methodological differences in the study protocols. Additionally, results indicate that there may be publication bias present. Overall, our findings are contrary to those of prior meta-analyses, suggesting limited impact of NAC on substance craving. However, the high heterogeneity and presence of publication bias identified warrants cautious interpretation of the meta-analytic outcomes.
N-乙酰半胱氨酸（NAC）可能成为治疗物质使用障碍（SUDs）患者物质使用及渴求的新型药物疗法，这可能是通过其调节谷氨酸的潜力实现的。尽管先前的荟萃分析总体上支持NAC在减轻渴求症状方面的疗效，但个别试验结果不一。本次更新荟萃分析的目的是：（1）检验NAC治疗SUD患者渴求症状的疗效；（2）探讨各试验间的亚组差异、偏倚风险和发表偏倚。2023年6月和7月对PubMed、Cochrane图书馆和ClinicalTrials.gov进行了数据库检索，以识别相关随机对照试验（RCT）。该荟萃分析包括9项试验，共分析了623名参与者的数据。临床试验中最常针对的物质是酒精（3/9；33.3%），其次是烟草（2/9；22.2%）和多种物质（2/9；22.2%）。进行了荟萃分析、亚组分析和逐一剔除分析，以检验对渴求症状和不良事件（AE）的治疗效果。进行了偏倚风险评估、Egger检验和漏斗图检验，以检验偏倚风险和发表偏倚。在荟萃分析中，NAC在减轻渴求症状方面并未显著优于安慰剂（标准化均数差=0.189，95%可信区间=-0.015-0.393）。荟萃分析中的异质性非常高（99.26%），表明研究结果可能受到研究方案中临床或方法学差异的影响。此外，结果表明可能存在发表偏倚。总体而言，我们的研究结果与先前的荟萃分析结果相反，表明NAC对物质渴求的影响有限。然而，所识别出的高异质性和发表偏倚使得对荟萃分析结果的解释需谨慎。
