Nine traditional Chinese herbal formulas for the treatment of depression: an ethnopharmacology, phytochemistry, and pharmacology review.
“In summary, the current evidence supports the efficacy of Chinese herbal formulas in the treatment of depression, but additional large-scale randomized controlled clinical trials and sophisticated pharmacology studies should be performed.”
Neuropsychiatr Dis Treat. 2016 Sep 20;12:2387-2402. eCollection 2016.
Feng DD, Tang T, Lin XP, Yang ZY, Yang S, Xia ZA, Wang Y, Zheng P, Wang Y, Zhang CH.
Depression is a major mental disorder, and is currently recognized as the second-leading cause of disability worldwide. However, the therapeutic effect of antidepressants remains unsatisfactory. For centuries, Chinese herbal formulas (CHFs) have been widely used in the treatment of depression, achieving better therapeutic effects than placebo and having fewer side effects than conventional antidepressants.
Here, we review the ethnopharmacology, phytochemistry, and pharmacology studies of nine common CHFs: “banxia houpo” decoction, “chaihu shugansan”, “ganmaidazao” decoction, “kaixinsan”, “shuganjieyu” capsules, “sinisan”, “wuling” capsules, “xiaoyaosan”, and “yueju”.
Eight clinical trials and seven meta-analyses have supported the theory that CHFs are effective treatments for depression, decreasing Hamilton Depression Scale scores and showing few adverse effects. Evidence from 75 preclinical studies has also elucidated the multitarget and multipathway mechanisms underlying the antidepressant effect of the nine CHFs. Decoctions, capsules, and pills all showed antidepressant effects, ranked in descending order of efficacy. According to traditional Chinese medicine theory, these CHFs have flexible compatibility and mainly act by soothing the liver and relieving depression.
This review highlights the effective treatment choices and candidate compounds for patients, practitioners, and researchers in the field of traditional Chinese medicine.
In summary, the current evidence supports the efficacy of CHFs in the treatment of depression, but additional large-scale randomized controlled clinical trials and sophisticated pharmacology studies should be performed.
A meta-analysis of the efficacy and safety of traditional Chinese medicine formula Ganmai Dazao decoction for depression.
The overall results suggest that Ganmai Dazao (GMDZ) decoction has few side effects and the potential as an antidepressant. Adding GMDZ to antidepressants reduces side effects and enhances efficacy of antidepressants.
J Ethnopharmacol. 2014 Apr 28;153(2):309-17. doi: 10.1016/j.jep.2014.02.046. Epub 2014 Mar 12.
Yeung WF, Chung KF, Ng KY, Yu YM, Ziea ET, Ng BF.
ETHNOPHARMACOLOGICAL RELEVANCE: Ganmai Dazao (GMDZ) decoction is a traditional Chinese herbal formula commonly used for the treatment of depression. The objective of this study was to assess the efficacy and safety of GMDZ, either alone or as co-therapy, for depression.
MATERIALS AND METHODS: We systematically searched key databases (9 Chinese and 7 English) up until May 2013 for randomized controlled trials (RCTs). The primary outcomes were effective rate and self-rated or clinician-rated severity of depression. The secondary outcome was the occurrence of adverse events. Methodological quality of the RCTs was assessed by the Cochrane׳s risk of bias assessment.
RESULTS: Ten RCTs were included. All were written in Chinese and the methodological quality was generally low. Pooled analysis of 5 studies which compared GMDZ with antidepressants showed that GMDZ was significantly more efficacious than antidepressants in effective rate (risk ratio: 1.14, 95% CI: 1.02 to 1.27, P=0.02, I(2)=0%), but comparable in Hamilton Depression Rating Scale (HDRS) score (mean difference: -2.10, 95% CI: -4.62 to -0.41, P=0.10, I(2)=92%). With regard to the other 5 studies which compared GMDZ plus antidepressants with antidepressants alone, there was no significant difference in effective rate (risk ratio: 1.24, 95% CI: 0.99 to 1.55, P=0.07, I(2)=93%), but the end-point HDRS score was significantly lower in GMDZ antidepressants combination (mean difference: -4.25, 95% CI: -6.50 to -2.00, P=0.0002, I(2)=96%). Adverse events were more common with antidepressants than GMDZ (rate ratio: 0.52, 95% CI: 0.32 to 0.82, P=0.005, I(2)=37%) and in antidepressants alone compared to GMDZ antidepressants combination (rate ratio: 0.23, 95% CI: 0.08 to 0.68, P=0.08, I(2)=0%).
CONCLUSION: The overall results suggest that GMDZ has few side effects and the potential as an antidepressant. Adding GMDZ to antidepressants reduces side effects and enhances efficacy of antidepressants. However, due to the small number of studies and their limitations, further studies with better methodological quality and more comprehensive safety assessment are needed to determine the benefits and risks of GMDZ in the treatment of depression.
Rapid antidepressant effects of Yueju: A new look at the function and mechanism of an old herbal medicine.
“Preclinical and clinical studies demonstrate that Yueju confers rapid antidepressant effects. The common mechanisms shared both for ketamine and Yueju, as well as the novel mechanism specific to Yueju are examined. Yueju and GJ may have great clinic applicability and further more detailed studies are warranted.”
J Ethnopharmacol. 2017 May 5;203:226-232. doi: 10.1016/j.jep.2017.03.042. Epub 2017 Mar 24.
Ren L, Chen G.
ETHNOPHARMACOLOGICAL RELEVANCE: Yueju is a traditional herbal medicine which consists of five herbs and formulated to treat depression-related syndromes 800 years ago. Yueju is still widely prescribed to treat conditions which include digestive dysfunction and depression. Recently, Yueju has been shown to promote a fast-onset antidepressant effect clinically and in preclinical studies. Because conventional antidepressants have a delayed onset in treating depression, the novelty of Yueju’s rapid antidepressant effect and its underlying mechanism are of great significance both clinically and scientifically.
AIM OF THE STUDY: To review the use of Yueju for treatment of mood-related syndromes, and particularly its use in depression. To evaluate recent evidence of Yueju rapid antidepressant actions, based on new findings at behavioral and molecular levels. To suggest direction for future studies to address further scientific issues.
MATERIALS AND METHODS: Reports regarding to the history and current use of Yueju are summarized. Recent progress on rapid antidepressant effects of Yueju, the crucial constituent, Gardenia jasminoides J.Ellis (GJ) and other herbs, are reviewed.
RESULTS: The medical need for rapid antidepressant actions, as well as breakthrough findings using ketamine and its limitations are introduced. Studies with Yueju using a number of acute, subacute and chronic behavioral paradigms are compared with ketamine. Findings from clinical reports also support the rapid action of Yueju. Studies examine the contribution of the constituent herb GJ, in rapid antidepressant effects. Importantly, research into the mechanism of Yueju or GJ’s antidepressant response indicate the importance of up-regulation in the neural circuit responsible for antidepressant activity, and highlight common and specific molecular signaling by Yueju that may explain why this herb formula has unique antidepressant activity.
Preclinical and clinical studies demonstrate that Yueju confers rapid antidepressant effects. The common mechanisms shared both for ketamine and Yueju, as well as the novel mechanism specific to Yueju are examined. Yueju and GJ may have great clinic applicability and further more detailed studies are warranted.
Acupuncture for depression.
This 2018 Cochrane Database systematic review found only low-quality evidence that “The reduction in severity of depression was less when acupuncture was compared with control acupuncture than when acupuncture was compared with no treatment control, although in both cases, results were rated as providing low-quality evidence …“
Cochrane Database Syst Rev. 2018 Mar 4;3:CD004046. doi: 10.1002/14651858.CD004046.pub4. [Epub ahead of print]
Smith CA, Armour M, Lee MS, Wang LQ, Hay PJ.
BACKGROUND: Depression is recognised as a major public health problem that has a substantial impact on individuals and on society. People with depression may consider using complementary therapies such as acupuncture, and an increasing body of research has been undertaken to assess the effectiveness of acupuncture for treatment of individuals with depression. This is the second update of this review.
OBJECTIVES: To examine the effectiveness and adverse effects of acupuncture for treatment of individuals with depression.To determine:
- Whether acupuncture is more effective than treatment as usual/no treatment/wait list control for treating and improving quality of life for individuals with depression.
- Whether acupuncture is more effective than control acupuncture for treating and improving quality of life for individuals with depression.• Whether acupuncture is more effective than pharmacological therapies for treating and improving quality of life for individuals with depression.
- Whether acupuncture plus pharmacological therapy is more effective than pharmacological therapy alone for treating and improving quality of life for individuals with depression.
- Whether acupuncture is more effective than psychological therapies for treating and improving quality of life for individuals with depression.
- Adverse effects of acupuncture compared with treatment as usual/no treatment/wait list control, control acupuncture, pharmacological therapies, and psychological therapies for treatment of individuals with depression.
SEARCH METHODS: We searched the following databases to June 2016: Cochrane Common Mental Disorders Group Controlled Trials Register (CCMD-CTR), Korean Studies Information Service System (KISS), DBPIA (Korean article database website), Korea Institute of Science and Technology Information, Research Information Service System (RISS), Korea Med, Korean Medical Database (KM base), and Oriental Medicine Advanced Searching Integrated System (OASIS), as well as several Korean medical journals.
SELECTION CRITERIA: Review criteria called for inclusion of all published and unpublished randomised controlled trials comparing acupuncture versus control acupuncture, no treatment, medication, other structured psychotherapies (cognitive-behavioural therapy, psychotherapy, or counselling), or standard care. Modes of treatment included acupuncture, electro-acupuncture, and laser acupuncture. Participants included adult men and women with depression diagnosed by Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV), Research Diagnostic Criteria (RDC), International Statistical Classification of Diseases and Related Health Problems (ICD), or Chinese Classification of Mental Disorders Third Edition Revised (CCMD-3-R). If necessary, we used trial authors’ definitions of depressive disorder.
DATA COLLECTION AND ANALYSIS: We performed meta-analyses using risk ratios (RRs) for dichotomous outcomes and standardised mean differences (SMDs) for continuous outcomes, with 95% confidence intervals (CIs). Primary outcomes were reduction in the severity of depression, measured by self-rating scales or by clinician-rated scales, and improvement in depression, defined as remission versus no remission. We assessed evidence quality using the GRADE method.
MAIN RESULTS: This review is an update of previous versions and includes 64 studies (7104 participants). Most studies were at high risk of performance bias, at high or unclear risk of detection bias, and at low or unclear risk of selection bias, attrition bias, reporting bias, and other bias.
Acupuncture versus no treatment/wait list/treatment as usual. We found low-quality evidence suggesting that acupuncture (manual and electro-) may moderately reduce the severity of depression by end of treatment (SMD -0.66, 95% CI -1.06 to -0.25, five trials, 488 participants). It is unclear whether data show differences between groups in the risk of adverse events (RR 0.89, 95% CI 0.35 to 2.24, one trial, 302 participants; low-quality evidence).
Acupuncture versus control acupuncture (invasive, non-invasive sham controls). Acupuncture may be associated with a small reduction in the severity of depression of 1.69 points on the Hamilton Depression Rating Scale (HAMD) by end of treatment (95% CI -3.33 to -0.05, 14 trials, 841 participants; low-quality evidence). It is unclear whether data show differences between groups in the risk of adverse events (RR 1.63, 95% CI 0.93 to 2.86, five trials, 300 participants; moderate-quality evidence).
Acupuncture versus medication. We found very low-quality evidence suggesting that acupuncture may confer small benefit in reducing the severity of depression by end of treatment (SMD -0.23, 95% CI -0.40 to -0.05, 31 trials, 3127 participants). Studies show substantial variation resulting from use of different classes of medications and different modes of acupuncture stimulation. Very low-quality evidence suggests lower ratings of adverse events following acupuncture compared with medication alone, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) (mean difference (MD) -4.32, 95% CI -7.41 to -1.23, three trials, 481 participants).
Acupuncture plus medication versus medication alone. We found very low-quality evidence suggesting that acupuncture is highly beneficial in reducing the severity of depression by end of treatment (SMD -1.15, 95% CI -1.63 to -0.66, 11 trials, 775 participants). Studies show substantial variation resulting from use of different modes of acupuncture stimulation. It is unclear whether differences in adverse events are associated with different modes of acupuncture (SMD -1.32, 95% CI -2.86 to 0.23, three trials, 200 participants; very low-quality evidence).
Acupuncture versus psychological therapy. It is unclear whether data show differences between acupuncture and psychological therapy in the severity of depression by end of treatment (SMD -0.5, 95% CI -1.33 to 0.33, two trials, 497 participants; low-quality evidence). Low-quality evidence suggests no differences between groups in rates of adverse events (RR 0.62, 95% CI 0.29 to 1.33, one trial, 452 participants).
The reduction in severity of depression was less when acupuncture was compared with control acupuncture than when acupuncture was compared with no treatment control, although in both cases, results were rated as providing low-quality evidence.
The reduction in severity of depression with acupuncture given alone or in conjunction with medication versus medication alone is uncertain owing to the very low quality of evidence.
The effect of acupuncture compared with psychological therapy is unclear.
The risk of adverse events with acupuncture is also unclear, as most trials did not report adverse events adequately. Few studies included follow-up periods or assessed important outcomes such as quality of life. High-quality randomised controlled trials are urgently needed to examine the clinical efficacy and acceptability of acupuncture, as well as its effectiveness, compared with acupuncture controls, medication, or psychological therapies.