Objective: To evaluate the efficacy and safety of Ganmai Dazao (GMDZ) decoction alone and in combination with antidepressant medication or psychotherapy for depression.
Methods: We searched seven electronic databases from inception to December 2025. Two assessors extracted the data and independently evaluated the methodological quality using the Cochrane risk of bias assessment.
Results: A total of 35 randomized controlled trials involving 3187 patients were included. Meta-analysis demonstrated that GMDZ decoction, either as monotherapy or in combination with antidepressants/psychotherapy, significantly reduced Hamilton Depression Scale (HAMD) scores (GMDZ group: standardized mean difference [SMD]: −0.63, 95% confidence interval [CI]: −1.01 to −0.26; combination therapy group: SMD: −1.87, 95% CI: −2.44 to −1.30), Hamilton Anxiety Scale scores (combination therapy group: mean difference [MD]: −4.23, 95% CI: −5.89 to −2.57), and Pittsburgh Sleep Quality Index scores (GMDZ group: MD: −3.56, 95% CI: −4.14 to −2.99; combination therapy group: MD: −3.60, 95% CI: −5.87 to −1.32), all statistically significant (P < .05). This effectively alleviated depressive and anxiety symptoms while improving sleep quality, with the combination therapy demonstrating greater efficacy in reducing HAMD scores. Regarding safety, adverse events primarily included nausea and dry mouth. The overall quality of the evidence was low.
Conclusion: GMDZ decoction effectively alleviated symptoms of depression and anxiety while improving sleep quality, with combination therapy demonstrating more pronounced effects in reducing HAMD scores. However, the included studies exhibited considerable heterogeneity, with some lacking clear allocation, concealment, or blinding protocols. More high-quality, large-sample, multicenter, randomized controlled trials are needed for further validation, given these limitations.
Funding
This study was supported by the Department of Science and Technology of Jilin Province (20240305077YY).
CRediT authorship contribution statement
Jiatong Dong: Data curation, investigation, software, visualization, and writing – original draft. Lisha Wang: Data curation, investigation, and methodology. Chenxuan Dong: Data curation, formal analysis, and investigation. Fangran Wang: Data curation, investigation, and writing – review & editing. Tianying Chang: Data curation, methodology, project administration, and writing – review & editing. Yingzi Cui: Conceptualization, methodology, supervision, validation, and writing – review & editing. Jiajuan Guo: Formal analysis, funding acquisition, supervision, and writing – review & editing.
Declaration of competing interest
The authors declare that there are no conflicts of interest.
| [1] |
Cui R. Editorial: a systematic review of depression. Curr Neuropharmacol. 2015; 13(4): 480.
|
| [2] |
Liu Q, He H, Yang J, Feng X, Zhao F, Lyu J . Changes in the global burden of depression from 1990 to 2017: findings from the Global Burden of Disease study. J Psychiatr Res. 2020; 126: 134-140.
|
| [3] |
Bromet E, Andrade LH, Hwang I, et al. Cross—national epidemiology of DSM—IV major depressive episode. BMC Med. 2011; 9: 90.
|
| [4] |
Shorey S, Ng ED, Wong CHJ . Global prevalence of depression and elevated depressive symptoms among adolescents: a systematic review and meta—analysis. Br J Clin Psychol . 2022; 61(2): 287-305.
|
| [5] |
Vas C, Jain A, Trivedi M, Jha MK, Mathew SJ . Pharmacotherapy for treatment—resistant depression: antidepressants and atypical antipsychotics. Psychiatr Clin. 2023; 46(2): 261-275.
|
| [6] |
Cuijpers P, Quero S, Dowrick C, Arroll B . Psychological treatment of depression in primary care: recent developments. Curr Psychiatry Rep. 2019; 21(12): 129.
|
| [7] |
Kessler RC, Soukup J, Davis RB, et al. The use of complementary and alternative therapies to treat anxiety and depression in the United States. Am J Psychiatr. 2001; 158(2): 289-294.
|
| [8] |
Dobrek L, Głowacka K . Depression and its phytopharmacotherapy: a narrative review. Int J Mol Sci. 2023; 24(5): 4772.
|
| [9] |
Zhuang W, Liu SL, Xi SY, et al. Traditional Chinese medicine decoctions and Chinese patent medicines for the treatment of depression: efficacies and mechanisms. J Ethnopharmacol. 2023; 307: 116272.
|
| [10] |
Fang ZN, Yang LL, Li Y, Zheng LM, Wang WD . Analysis of frequency of treatment for depression related diseases in Chinese medical classics. China J Tradit Chin Med Pharm. 2019; 34(4): 1734-1736 [Chinese].
|
| [11] |
Guo LH, Li CP . Translation: Zang Zao. Henan J Tradit Chin Med. 2009; 29(2): 113 [Chinese].
|
| [12] |
Zhang B, Ji J, Zhang X, et al. Gan—Mai—Da—Zao decoction ameliorates depressive—like behaviors in CUMS mice via the microbiota—metabolism—inflammation axis. Phytomedicine. 2025; 145: 157018.
|
| [13] |
Yeung WF, Chung KF, Ng KY, Yu YM, Tat—Chi Ziea E, Fung—Leung Ng B . A meta—analysis of the efficacy and safety of traditional Chinese medicine formula Ganmai Dazao decoction for depression. J Ethnopharmacol. 2014; 153(2): 309-317.
|
| [14] |
Kennedy SH, Ceniti AK . Unpacking major depressive disorder: from classification to treatment selection. Can J Psychiatr. 2018; 63(5): 308-313.
|
| [15] |
Kverno KS, Mangano E . Treatment—resistant depression: approaches to treatment. J Psychosoc Nurs Ment Health Serv. 2021; 59(9): 7-11.
|
| [16] |
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372: n71.
|
| [17] |
Higgins J, Thomas CJ, Cumpston M, et al. Cochrane handbook for systematic reviews of interventions. https://training.cochrane.org/handbook. Accessed June 20, 2024.
|
| [18] |
Higgins JPT, Thompson SG, Deeks JJ, Altman DG . Measuring inconsistency in meta—analyses. BMJ. 2003; 327(7414): 557-560.
|
| [19] |
Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004; 328(7454): 1490.
|
| [20] |
GRADEpro Web site. GRADEpro guideline development tool. https://www.gradepro.org/. Accessed January 19, 2026.
|
| [21] |
Balshem H, Helfand M, Schünemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011; 64(4): 401-406.
|
| [22] |
He YF, Tan B . Clinical observation on the treatment of depression with Ganmai Dazao decoction combined with clomipramine. Lishizhen Med Mater Med Res. 2006; 10: 2026-2027 [Chinese].
|
| [23] |
Gong JQ . Treatment of depression and anxiety with adjuvant Ganmai Dazao decoction in 38 convalescent patients. Acta Chin Med Pharmacol. 2008; 36(6): 62-64 [Chinese].
|
| [24] |
Li X, Tong LG . Treatment of post—PCI depression with modified Ganmai Dazao decoction: a report of 32 cases. Zhejiang J Tradit Chin Med. 2008;(2): 88-89 [Chinese].
|
| [25] |
Meng HQ, Suo JJ, Quan YP . A clinical study of the efficacy Ganmai Dazao Tang in treatment of post—stroke depression. Liaoning J Tradit Chin Med. 2008; 35(3): 384-385 [Chinese].
|
| [26] |
Wang YL, Gao Y, Wu LZ, Yin H . Clinical observation on modified Ganmai Dazao decoction in treating 30 cases of malignant tumor complicated with depression. Jiangsu J Tradit Chin Med. 2008; 40(12): 44-45 [Chinese].
|
| [27] |
Tang P, Liu JM . Clinical observation on Ganmai Dazao decoction in treating 38 cases of post—stroke depression. Sichuan Med J. 2009; 30(5): 709-710 [Chinese].
|
| [28] |
Zhou XY, Qin XD, Geng LF . Clinical observation on Ganmai Dazao decoction in treating 30 cases of post—stroke depression. J Sichuan Tradit Chin Med. 2009; 27(10): 75-76 [Chinese].
|
| [29] |
Xun X, He Q . Clinical observation on the treatment of 30 cases of post stroke depression with combination of TCM and Western Medicine. China Med Her. 2010; 7(18): 90-91 [Chinese].
|
| [30] |
Yin YX . Clinical observation on adjuvant therapy of Ganmai Dazao decoction for depression. Guide Chin Med. 2010; 8(29): 277-278 [Chinese].
|
| [31] |
Xu TS, Wan Q . Clinical study on modified Ganmai Dazao decoction in treating 32 cases of depression. Jiangsu J Tradit Chin Med. 2011; 43(9): 24-25 [Chinese].
|
| [32] |
Li H, Yu G, Li S, Tan Y . The efficacy of combined herbal medicine with paroxetine in the treatment of generalized anxiety disorder. China J Health Psychol. 2012; 20(4): 491-493 [Chinese].
|
| [33] |
Wu J, Wang HX, Wang CC . Clinical observation on therapeutic effect of integrated traditional Chinese and Western medicine in treating 60 cases of post—stroke depression. J Sichuan Tradit Chin Med. 2012; 30(9): 71-72 [Chinese].
|
| [34] |
Lin RF . Clinical observation on modified Ganmai Dazao decoction in treating 30 cases of depression (malnourishment of heart spirit pattern). Guangming J Chin Med. 2013; 28(11): 2456-2457 [Chinese].
|
| [35] |
Ma XJ, Zhao J, Feng ZY, et al. Effects of modified Ganmai Dazao decoction on neuroendocrine system in patients with climacteric depression. China J Chin Mater Med. 2014; 39(23): 4680-4684 [Chinese].
|
| [36] |
Zhang Y, Lyu S, Wang P, Liu J, Guo N . Supplemented Ganmai—Dazao decoction for malignant tumor—related depression: comparison with flupentixol and melitracen tablets. Int J Trad Chin Med. 2015; 37(6): 494-497 [Chinese].
|
| [37] |
Zhang E, Gao P, Chen P . Clinical observation on modified Ganmai Dazao decoction combined with flupentixol and melitracen tablets in treating 60 cases of postpartum depression. J Tradit Chin Med Res. 2015; 28(10): 19-21 [Chinese].
|
| [38] |
Shao Y . Effects of modified Ganmai Dazao decoction on sleep disorders and depressive states in postpartum women. Chin J Clin Rational Drug Use. 2016; 9(2): 38-39 [Chinese].
|
| [39] |
Xie XQ, Wang XJ . Medicinal and edible homologous and traditional Chinese medicine. China Health Care Nutr. 2016; 26(25): 27 [Chinese].
|
| [40] |
Xu DY, Zhao J, Yi J . Therapeutic effect of modified Ganmai Dazao decoction on yang—deficiency type menopausal depression and its influence on the neuroendocrine system. Mod J Integr Tradit Chin West Med. 2017; 26(17): 1910-1912 [Chinese].
|
| [41] |
Xu M . Clinical observation on integrated traditional Chinese and Western medicine in treating anxiety disorders after cerebral infarction. Guangming J Chin Med. 2017; 32(5): 724-726 [Chinese].
|
| [42] |
Ye JJ, Li G, Jia JH . Clinical observation of supplemented Ganmaidazao decoction in the treatment of 40 cases of cancer related depression. Smart Healthc. 2017; 3(9): 114-115 [Chinese].
|
| [43] |
Cao KY, Zheng K . Effects of modified Ganmai Dazao decoction on chemotherapy efficacy and sleep quality in patients with non—small cell lung cancer and depression. Mod Pract Med. 2018; 30(10): 1315-1317 [Chinese].
|
| [44] |
Chen S. Effect of modified Ganmai Dazao decoction on peri—menopausal patients with severe primary depression and its effects on neurotransmitters and inflammatory factors. Mod J Integr Tradit Chin West Med. 2018; 27(20): 2196—2198, 2202 [Chinese].
|
| [45] |
Huang J, Shen H, Wu Y, Zhou X, Li M . Effect of Jiawei Ganmai Dazao decoction combined with amitriptyline in patients with depression and anxiety after breast tumor resection and its effect on sleep and quality of life. Mod J Integr Tradit Chin West Med. 2019; 28(14): 1496-1499 [Chinese].
|
| [46] |
Li Y . Clinical efficacy analysis of Ganmai Dazao decoction for post—stroke depression. Guide Chin Med. 2019; 17(23): 162-163 [Chinese].
|
| [47] |
Li J, Yang D, Wang B, Shen J, Kang P . Effect of Jiawei Ganmai Dazao decoction combined with Deanxit in the treatment of depression after post stroke. World Chin Med. 2020; 15(22): 3447—3450, 3454 [Chinese].
|
| [48] |
Liu QY, Liu YZ . The effect of Jiawei Ganmai Dazao decoction in the treatment of female menopausal depression and its influence on psychological status. Psychol Monogr (Gen Appl). 2020; 15(21): 221-222 [Chinese].
|
| [49] |
Zeng J, Li A, Li L, Luo C, Zhang Y . Clinical observation on Ganmai Dazao decoction combined with venlafaxine in the treatment of post—stroke depression. Guangming J Chin Med. 2021; 36(21): 3679-3681 [Chinese].
|
| [50] |
Li GX . Clinical observation on modified Ganmai Dazao decoction in treating menopausal depression of yang—deficiency type. Diet Health. 2022;(16): 17-20 [Chinese].
|
| [51] |
Liu SJ, Hu XQ . Clinical study on Ganmai Dazao decoction in treating perimenopausal anxiety disorders of liver stagnation and kidney deficiency. J Pract Tradit Chin Med. 2022; 38(6): 898-899 [Chinese].
|
| [52] |
Wang J, Li Y, Wang H . Clinical effects of Ganmai Dazao Tang and escitalopram in the treatment of depression and the analysis of its safety. West J Tradit Chin Med. 2022; 35(7): 76-79 [Chinese].
|
| [53] |
Han QL, Lu WJ, Li SD . Effect of modified Ganmai Dazao decoction on menopausal depression in women and its influence on psychological status. Doctor. 2023; 8(1): 98-100 [Chinese].
|
| [54] |
Yu QY, Yu ZH, Dai YL . Application of Ganmai Dazao decoction combined with escitalopram in the treatment of depression. Psychol Monogr (Gen Appl). 2023; 18(12): 141-143 [Chinese].
|
| [55] |
Fei G, Yang F, Wang M, Shen Y, Li X, Zhao X . Effect of supplemented Ganmai Dazao decoction on intestinal microbiota and serum 5—HT in postpartum depression patients with deficiency of qi and blood. Chin J Microecol. 2024; 36(2): 211-217 [Chinese].
|
| [56] |
Hu K, Zhang R, Zhang B, Sun YL, Hu YK, Zhang ML . Influence of Ganmai Dazao decoction on depression. Guangming J Chin Med. 2024; 39(12): 2416-2418 [Chinese].
|
| [57] |
Culpepper L . Impact of anxious symptoms and comorbid anxiety disorders on functional impairment in depressed patients. J Clin Psychiatry. 2016; 77(5): e604.
|
| [58] |
Stone MB, Yaseen ZS, Miller BJ, Richardville K, Kalaria SN, Kirsch I . Response to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration: individual participant data analysis. BMJ. 2022; 378: e067606.
|
| [59] |
Borbély E, Simon M, Fuchs E, Wiborg O, Czéh B, Helyes Z . Novel drug developmental strategies for treatment—resistant depression. Br J Pharmacol. 2022; 179(6): 1146-1186.
|
| [60] |
Li YX, Cheng KC, Hsu CT, Cheng JT, Yang TT . Major plant in herbal mixture Gan—Mai—Da—Zao for the alleviation of depression in rat models. Plants. 2022; 11(3): 258.
|
| [61] |
Chen HS, Gu LJ, Yang YX, Guo JY . GABA and 5—HT systems are involved in the anxiolytic effect of Gan—Mai—Da—Zao decoction. Front Neurosci. 2019; 12: 1043.
|
| [62] |
Fang H, Tu S, Sheng J, Shao A . Depression in sleep disturbance: a review on a bidirectional relationship, mechanisms and treatment. J Cell Mol Med. 2019; 23(4): 2324-2332.
|
| [63] |
Zhang M, Ning G, Shou C, Lu Y, Hong D, Zheng X . Inhibitory effect of jujuboside A on glutamate—mediated excitatory signal pathway in hippocampus. Planta Med. 2003; 69(8): 692-695.
|
| [64] |
Zeng L, He T, Li H, et al. Core GRADE methodological system: core approach for evidence quality assessment and guideline development in GRADE. Eval Anal Drug Use Hosp China. 2025; 25(11): 1281—1285, 1290 [Chinese].
|
| [65] |
Dai L, Cheng CW, Tian R, et al. Standard protocol items for clinical trials with traditional Chinese medicine 2018: recommendations, explanation and elaboration (SPIRIT—TCM extension 2018). Chin J Integr Med. 2019; 25(1): 71-79.
|
| [66] |
Cheng CW, Wu TX, Shang HC, et al. CONSORT extension for Chinese herbal medicine formulas 2017: recommendations, explanation, and elaboration (traditional Chinese version). Ann Intern Med. 2017; 167(2): W7-W20.
|
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