Huperzine A for treatment of cognitive impairment in major depressive disorder: a systematic review of randomized controlled trials.
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.


OBJECTIVE
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.
The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China.
Wei
W
Zheng
China Clinical Research Center for Mental Disorders, Beijing, China, and Center of Depression, Beijing Institute for Brain Disorders, Beijing, China ; Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
Ying-Qiang
YQ
Xiang
School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Australia ; University of Notre Dame Australia / Marian Centre, Perth, Australia.
Gabor S
GS
Ungvari
Department of Psychiatry, Chinese University of Hong Kong, Hong Kong SAR, China.
F K Helen
FK
Chiu
Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia.
Chee
C
H Ng
Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
Ying
Y
Wang
Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao SAR, China.
Yu-Tao
YT
Xiang
adjunctive treatment; cognitive function; depression; huperzine A; meta-analysis