Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, Huaxi MR Research Center, West China Hospital, Sichuan University, Sichuan, China.
Bipolar Disord. 2021 Nov;23(7):707-714. doi: 10.1111/bdi.13039. Epub 2021 Jan 15.
Previous studies and meta-analyses suggested that N-acetylcysteine (NAC) was superior to placebo in improving depression in bipolar disorder. However, more recent data, including two larger trials, found that NAC was no more effective than placebo. We conducted a meta-analysis to appraise the possible efficacy of NAC in treating bipolar depression.
A systematic review and meta-analysis of double-blind, placebo-controlled trials of NAC as a treatment augmentation strategy for bipolar depression was carried out in PubMed (1966-2020). We utilized random-effect analysis to evaluate improvement in depressive symptoms from baseline to endpoint as the primary efficacy measure.
Six trials including 248 patients were included. Treatment augmentation with NAC showed a moderate effect size favoring NAC over placebo (d = 0.45, 95% C.I.: 0.06-0.84). There was substantial heterogeneity (I = 49%). Meta-regression analyses did not identify any moderator that might explain variation in heterogeneity, including baseline depressive symptom scores, mean NAC dose, or duration of study.
Results from six clinical trials suggest that treatment augmentation with NAC for bipolar depression appears to be superior to placebo, with a moderate effect size, but a large confidence interval. Larger clinical trials, investigating possible moderating factors, such as NAC dose, treatment duration, baseline depression severity, or chronicity of illness, are warranted.
先前的研究和荟萃分析表明，N-乙酰半胱氨酸（NAC）在改善双相情感障碍中的抑郁症状方面优于安慰剂。然而，最近的数据，包括两项更大规模的试验，发现 NAC 并不比安慰剂更有效。我们进行了一项荟萃分析，以评估 NAC 治疗双相情感障碍抑郁的可能疗效。
在 PubMed（1966-2020 年）中对 NAC 作为双相情感障碍抑郁增效治疗的双盲、安慰剂对照试验进行了系统评价和荟萃分析。我们采用随机效应分析来评估从基线到终点抑郁症状的改善作为主要疗效指标。
纳入了六项试验，共 248 名患者。NAC 的增效治疗显示出对 NAC 优于安慰剂的中等效应大小（d=0.45，95%置信区间：0.06-0.84）。存在很大的异质性（I=49%）。元回归分析未发现任何可能解释异质性变异的调节因素，包括基线抑郁症状评分、NAC 平均剂量或研究持续时间。
六项临床试验的结果表明，NAC 治疗双相情感障碍抑郁似乎优于安慰剂，具有中等的效应大小，但置信区间较大。需要更大规模的临床试验，研究可能的调节因素，如 NAC 剂量、治疗持续时间、基线抑郁严重程度或疾病慢性程度。
