AccScience Publishing / HPR / Online First / DOI: 10.36922/HPR026070036
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RESEARCH ARTICLE

Anti-inflammatory pharmacotherapy for depressive disorders: A network meta-analysis of double-blind, randomised, controlled, parallel-group clinical trials

Yan Bo1* ,  Youwei Wang2
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1 Department of Medicine, Northwest Minzu University, Lanzhou, Gansu, China
2 School of Medicine, Beihua University, Jilin City, Jilin, China
HPR, 026070036 https://doi.org/10.36922/HPR026070036
Received: 9 February 2026 | Revised: 21 June 2026 | Accepted: 1 July 2026 | Published online: 16 July 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Background: Neuroinflammation has emerged as a potential biological mechanism underlying depressive disorders and represents an increasingly investigated target for therapeutic intervention.

Objective: To compare the effects of pharmacological interventions evaluated within an inflammation-related framework on depressive symptom severity and inflammatory biomarker outcomes.

Methods: Randomised controlled trials reporting pharmacological interventions for depressive disorders were included. A frequentist fixed-effects network meta-analysis was conducted for depressive symptom severity at the end of randomised treatment. Treatments were ranked using surface under the cumulative ranking curve values. Exploratory pairwise meta-analyses were performed separately for tumour necrosis factor-alpha, interleukin-6, interferon-gamma, C-reactive protein, and interleukin-2.

Results: Eleven randomised controlled trial reports contributed to a sparse network of 10 active interventions. Using a frequentist fixed-effect network meta-analysis, escitalopram oxalate showed the largest estimated reduction in depressive symptom severity relative to the reference control node (mean difference [MD]: −13.03; 95% confidence interval [CI]: −24.54 to −1.52). Ketamine 0.5 mg/kg (MD: −5.16; 95% CI: −8.81 to −1.51) and selective serotonin reuptake inhibitor plus glycyrrhizic acid (MD: −4.35; 95% CI: −7.16 to −1.55) also showed estimates favouring intervention. Fluoxetine, fluoxetine plus triiodothyronine, infliximab, ketamine 0.2 mg/kg, minocycline, sumac, and vortioxetine plus celecoxib did not show statistically precise differences from the reference control node. Exploratory biomarker analyses showed no consistent pooled differences in inflammatory markers and substantial heterogeneity for several biomarkers.

Conclusion: Current evidence does not support a consistent class-wide benefit of inflammation-informed pharmacotherapy for depressive disorders. Although several interventions showed potentially favourable effects on depressive symptom severity, the evidence network was sparse, and most comparisons were based on single trials. Future trials should enrol biologically defined patient subgroups and use standardised clinical and biomarker outcomes.

Keywords
Depression disorders
Anti-inflammatory strategy
Randomised controlled trials
Pharmaceutical treatment
Network meta-analysis
Funding
None.
Conflict of interest
The authors declare no competing interests.
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