Department of Medical and Clinical Psychology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, Maryland, USA.
Addict Biol. 2024 Nov;29(11):e70001. doi: 10.1111/adb.70001.
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 this updated meta-analysis were to (1) examine the efficacy of NAC in treating symptoms of craving in individuals with 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 analysed 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 the treatment effect on craving symptoms and adverse events (AEs). Risk of bias assessments, Egger's tests and funnel plot tests were conducted to examine the 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 a 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）可能作为一种新的药物治疗方法，用于治疗物质使用障碍（SUD）患者的物质使用和物质渴求，其作用机制可能是通过调节谷氨酸。尽管先前的荟萃分析普遍支持 NAC 降低渴求症状的疗效，但个别试验的结果却存在差异。本项更新的荟萃分析旨在：（1）评估 NAC 治疗 SUD 患者渴求症状的疗效；（2）探索试验间的亚组差异、偏倚风险和发表偏倚。2023 年 6 月至 7 月，我们对 PubMed、Cochrane Library 和 ClinicalTrials.gov 数据库进行了检索，以确定相关的随机对照试验（RCT）。该荟萃分析共纳入 9 项试验，分析了来自 623 名参与者的数据。临床试验中最针对的物质是酒精（3/9；33.3%），其次是烟草（2/9；22.2%）和多种物质（2/9；22.2%）。进行荟萃分析、亚组分析和逐个剔除分析，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。NAC 在降低渴求症状方面并不优于安慰剂（SMD=0.189，95%CI=-0.015-0.393）。荟萃分析中的异质性非常高（99.26%），表明研究方案中的临床或方法学差异可能影响了研究结果。此外，结果表明可能存在发表偏倚。总体而言，我们的发现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，高异质性和发表偏倚的存在，需要对荟萃分析结果进行谨慎解释。
