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. 2016 Apr 25;28(2):64-71.
doi: 10.11919/j.issn.1002-0829.216003.

Huperzine A for Treatment of Cognitive Impairment in Major Depressive Disorder: A Systematic Review of Randomized Controlled Trials

Free PMC article

Huperzine A for Treatment of Cognitive Impairment in Major Depressive Disorder: A Systematic Review of Randomized Controlled Trials

Wei Zheng et al. Shanghai Arch Psychiatry. .
Free PMC article


Background: Acetylcholinesterase (AChE) inhibitors have been shown to be effective in treating cognitive impairment in animal models and in human subjects with major depressive disorder (MDD). Huperzine A (HupA), a Traditional Chinese Medicine derived from a genus of clubmosses known as Huperzineserrata, is a powerful AChE inhibitor that has been used as an adjunctive treatment for MDD, but no meta-analysis on HupA augmentation for MDD has yet been reported.

Aim: Conduct a systematic review and meta-analysis of randomized controlled trials (RCTS) about HupA augmentation in the treatment of MDD to evaluate its efficacy and safety.

Methods: Two evaluators independently searched nine English-language and Chinese-language databases, selected relevant studies that met pre-determined inclusion criteria, extracted data about outcome and safety, and conducted quality assessments and data synthesis.

Results: Three low-quality RCTs (pooled n=238) from China were identified that compared monotherapy antidepressant treatment for depression versus combined treatment with antidepressants and HupA. Participants in the studies ranged from 16 to 60 years of age. The average duration of adjunctive antidepressant and HupA treatment in the studies was only 6.7 weeks. All three studies were open label and non-blinded, so their overall quality was judged as poor. Meta-analysis of the pooled sample found no significant difference in the improvement in depressive symptoms between the two groups (weighted mean difference: -1.90 (95%CI: -4.23, 0.44), p=0.11). However, the adjunctive HupA group did have significantly greater improvement than the antidepressant only group in cognitive functioning (as assessed by the Wisconsin Card Sorting Test and the Wechsler Memory Scale-Revised) and in quality of life. There was no significant difference in the incidence of adverse drug reactions between groups.

Conclusions: The data available on the effectiveness and safety of adjunctive treatment using HupA in patients with MDD who are receiving antidepressants is insufficient to arrive at a definitive conclusion about its efficacy and safety. Pooling of the data from three low-quality RCTs from China found no advantage of adjunctive HupA in the treatment of depressive symptoms, but adjunctive treatment with HupA was associated with a faster resolution of the cognitive symptoms that frequently accompany MDD.

背景: 乙酰胆碱酯酶(Acetylcholinesterase, AChE)抑制剂在重性抑郁障碍(Major Depressive Disorder, MDD)的动物模型和人类患者中已被证实可以有效地治疗认知障碍。石杉碱甲(Huperzine A, HupA)是一种来自于被称为蛇足石杉(Huperzineserrata)的石松属传统中医药,是一种强有力的AChE抑制剂,已被用于抑郁症的辅助治疗,但有尚无关石杉碱甲对MDD的强化治疗作用的meta分析。.

目标: 对有关石杉碱甲强化治疗抑郁症的随机对照试验进行系统综述和meta分析,评估其疗效及安全性。.

方法: 两位评估者独立检索9个英文和中文数据库,选择符合预先确定的纳入标准的相关研究,提取有关疗效和安全性的数据,并进行质量评估和数据拟合合成。.

结果: 纳入了三项中国低质量的随机对照试验(总共n=238),这些试验比较了单用抗抑郁药治疗抑郁症与抗抑郁药和石杉碱甲的联合治疗,试验中的被试从16岁到60岁。研究中石杉碱甲辅助抗抑郁药治疗的平均时间仅为6.7周。这三项研究都是公开标签未使用盲法,所以他们的总体质量评定为差。总体样本的Meta分析发现两组抑郁症状的改善没有显著性差异(差异加权差为-1.90,95%CI可信区间为-4.23至0.44,p=0.11)。然而,石杉碱甲辅助治疗组比单用抗抑郁药治疗组在认知功能和生活质量方面有显著改善(如威斯康星卡片分类测验、韦氏记忆量表修订的评估)。组间药物不良反应的发生率无显著性差异。.

结论: 有关在接受抗抑郁药的MDD患者使用HupA辅助治疗的疗效和安全性的可获取数据不足,难以得出有关其疗效和安全性的明确结论。汇集国内3项低质量的RCT数据没有发现采用辅助使用HupA治疗抑郁症状的优势,但辅助使用HupA与更快改善经常伴随MDD出现的认知症状相关。.

中文全文: 本文全文中文版从2016年8月25日起在可供免费阅览下载.

Keywords: adjunctive treatment; cognitive function; depression; huperzine A; meta-analysis.

Conflict of interest statement

The authors report no conflict of interest in conducting this study and preparing the manuscript.


Figure 1
Figure 1. Identification of included studies
Figure 2
Figure 2
Adjunctive Huperzine A for MDD: forest plot for improvement in depressive symptoms assessed by change in total score of the Hamilton Depression Scale

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Grant support

The study was supported by the Start-up Research Grant (SRG2014-00019-FHS) and the Multi-Year Research Grant (MYRG2015-00230-FHS) from the University of Macau. Trial registration number: CRD42015024796 (

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