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。.
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.
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