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Microbiota-Targeted Therapies for Adults with Major Depressive Disorder Compared with Antidepressants: A Systematic Review and Network Meta-Analysis

24 Pages Posted: 10 May 2023

See all articles by Shilin Zhao

Shilin Zhao

The Chinese University of Hong Kong - Department of Medicine & Therapeutics

Suisha Liang

The University of Hong Kong - School of Public Health

Jun Tao

The University of Hong Kong - School of Public Health

Ye Peng

The Chinese University of Hong Kong - Department of Medicine & Therapeutics

Siqi Chen

Shenzhen Maternity & Child Healthcare Hospital

Hogan Wai

The University of Hong Kong - School of Public Health

Feng-Ying Chung

Taipei Medical University - Department of Internal Medicine

Zhen Sin

The Chinese University of Hong Kong (CUHK) - The Jockey Club School of Public Health and Primary Care

Matthew Wong

The Chinese University of Hong Kong - Department of Medicine & Therapeutics

Wing Chang

The University of Hong Kong - Department of Psychiatry

Michael Yuxuan Ni

The University of Hong Kong - School of Public Health

Francis KL Chan

The Chinese University of Hong Kong - Department of Medicine & Therapeutics

Siew C. Ng

The Chinese University of Hong Kong - Department of Medicine & Therapeutics

Hein Min Tun

The Chinese University of Hong Kong - Department of Medicine & Therapeutics

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Abstract

Background: Despite recent advances in antidepressants in treating major depression (MDD), their usage is marred by adverse effects and social stigmas. Probiotics may be an efficacious adjunct or standalone treatment, potentially circumventing the aforementioned issues with antidepressants. However, there is a lack of head-to-head clinical trials between these two interventions. As such, we aim to compare the efficacy and acceptability of these two interventions in treating MDD. 

Methods: We searched six e-databases for double-blinded, randomized controlled trials published between 2015 and 2022. We included placebo-controlled trials of antidepressants and microbiota-targeted interventions used for the treatment of MDD adults (≥18 years old). Standardized mean difference (SMD) of depressive symptom scores from individual trials were pooled for network meta-analysis (PROSPERO No. CRD42020222305). 

Findings: Forty-two eligible trials covering 22 interventions were identified, of which 16 were found to be effective in MDD treatment and the certainty of evidence was moderate to very low. Compared to placebo, SMDs ranged from -0.16 (95% credible interval [CrI] -0.30 to -0.04) for venlafaxine and -0.81 (-1.06 to -0.52) for escitalopram. Probiotics administered with antidepressants were found to be more effective than both placebo and venlafaxine alone in reducing MDD symptoms (SMD, 95% CrI: -0.59, -0.82 to -0.34 and -0.41, -0.70 to -0.14, respectively). Long-term treatment (≥8 weeks) using probiotics showed the same tolerability as antidepressants. In addition, probiotics ranked the second highest in the treatment hierarchy after escitalopram. 

Interpretation: Probiotics, compared with antidepressants and placebo, may be efficacious as an adjunct or standalone therapy for treating MDD.

Funding: This study was funded by the Health and Medical Research Fund of the Food and Health Bureau (Ref. No.: CFS-HKU2), the Government of the Hong Kong SAR.

Declaration of Interest: The authors declare no competing interests.

Keywords: comparative efficacy, microbiota-targeted therapies, probiotics, antidepressants, major depressive disorder, network meta-analysis

Suggested Citation

Zhao, Shilin and Liang, Suisha and Tao, Jun and Peng, Ye and Chen, Siqi and Wai, Hogan and Chung, Feng-Ying and Sin, Zhen and Wong, Matthew and Chang, Wing and Ni, Michael Yuxuan and Chan, Francis KL and Ng, Siew C. and Tun, Hein Min, Microbiota-Targeted Therapies for Adults with Major Depressive Disorder Compared with Antidepressants: A Systematic Review and Network Meta-Analysis. Available at SSRN: https://ssrn.com/abstract=4442854 or http://dx.doi.org/10.2139/ssrn.4442854

Shilin Zhao

The Chinese University of Hong Kong - Department of Medicine & Therapeutics ( email )

Suisha Liang

The University of Hong Kong - School of Public Health ( email )

Jun Tao

The University of Hong Kong - School of Public Health ( email )

Ye Peng

The Chinese University of Hong Kong - Department of Medicine & Therapeutics ( email )

Siqi Chen

Shenzhen Maternity & Child Healthcare Hospital ( email )

Hogan Wai

The University of Hong Kong - School of Public Health ( email )

Feng-Ying Chung

Taipei Medical University - Department of Internal Medicine ( email )

Zhen Sin

The Chinese University of Hong Kong (CUHK) - The Jockey Club School of Public Health and Primary Care ( email )

Matthew Wong

The Chinese University of Hong Kong - Department of Medicine & Therapeutics ( email )

Wing Chang

The University of Hong Kong - Department of Psychiatry ( email )

Michael Yuxuan Ni

The University of Hong Kong - School of Public Health ( email )

Francis KL Chan

The Chinese University of Hong Kong - Department of Medicine & Therapeutics ( email )

Siew C. Ng

The Chinese University of Hong Kong - Department of Medicine & Therapeutics ( email )

Hein Min Tun (Contact Author)

The Chinese University of Hong Kong - Department of Medicine & Therapeutics ( email )

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