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Original research
Efficacy and safety of anti-inflammatory agents for the treatment of major depressive disorder: a systematic review and meta-analysis of randomised controlled trials
  1. Shuang Bai1,
  2. Wenliang Guo2,
  3. Yangyang Feng1,
  4. Hong Deng1,
  5. Gaigai Li1,
  6. Hao Nie1,
  7. Guangyu Guo1,
  8. Haihan Yu1,
  9. Yang Ma1,
  10. Jiahui Wang1,
  11. Shiling Chen1,
  12. Jie Jing1,
  13. Jingfei Yang1,
  14. Yingxin Tang1,
  15. Zhouping Tang1
  1. 1 Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  2. 2 Department of Neurology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  1. Correspondence to Professor Zhouping Tang, Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; ddjtzp{at}; Dr Yingxin Tang; yingxintang{at}


Objectives To systematically review the efficacy and safety of anti-inflammatory agents for patients with major depressive disorders.

Methods We searched the literature to identify potentially relevant randomised controlled trials (RCTs) up to 1 January 2019. The primary outcome was efficacy, measured by mean changes in depression score from baseline to endpoint. Secondary outcomes included response and remission rates and quality of life (QoL). Safety was evaluated by incidence of classified adverse events. Heterogeneity was examined using the I2 and Q statistic. Pooled standard mean differences (SMDs) and risk ratios (RRs) were calculated. Subgroup meta-analyses were conducted based on type of treatment, type of anti-inflammatory agents, sex, sponsor type and quality of studies.

Results Thirty RCTs with 1610 participants were included in the quantitative analysis. The overall analysis pooling from 26 of the RCTs suggested that anti-inflammatory agents reduced depressive symptoms (SMD −0.55, 95% CI −0.75 to −0.35, I2=71%) compared with placebo. Higher response (RR 1.52, 95% CI 1.30 to 1.79, I2=29%) and remission rates (RR 1.79, 95% CI 1.29 to 2.49, I2=41%) were seen in the group receiving anti-inflammatory agents than in those receiving placebo. Subgroup analysis showed a greater reduction in symptom severity in both the monotherapy and adjunctive treatment groups. Subgroup analysis of non-steroidal anti-inflammatory drugs, omega-3 fatty acids, statins and minocyclines, respectively, disclosed significant antidepressant effects for major depressive disorder (MDD). For women-only trials, no difference in changes of depression severity was found between groups. Subanalysis stratified by sponsor type and study quality led to the same outcomes in favour of anti-inflammatory agents in both subgroups. Changes of QoL showed no difference between the groups. Gastrointestinal events were the only significant differences between groups in the treatment periods.

Conclusions Results of this systematic review suggest that anti-inflammatory agents play an antidepressant role in patients with MDD and are reasonably safe.

  • antidepressant effects
  • anti-inflammatory agents
  • major depressive disorder
  • meta-analysis
  • systematic review

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  • Contributors SB, WG, YF, HD, GL, ZT and YT were responsible for study concept and design. SB, WG, YF, HD, GL, HN, GG, HY, YM, JW, SC, JJ, JY, ZT and YT were responsible for the acquisition, analysis and interpretation of data. SB, WG, SC, JJ and JY drafted the manuscript. SB, WG, YF, HD, ZT and YT critically revised the manuscript for important intellectual content. ZT obtained the funding and was responsible for study supervision.

  • Funding This study was supported by funds from the National Natural Science Foundation of China, grant number: 81873750, URL:, recipient: ZPT.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.