Comparative Efficacy and Acceptability of Anti-inflammatory Agents on Major Depressive Disorder: A Network Meta-Analysis

Abstract

Background: With the growing importance of research about the association between neuroinflammation and major depressive disorder (MDD), anti-inflammatory agents have been used as a new antidepressant therapy in clinical practice. We conducted a network meta-analysis (NMA) with up-to-date evidence to compare different anti-inflammatory agents for improving the treatment of MDD patients.Methods: To identify eligible randomized clinical trials, four databases (i.e, the Cochrane Library, Web of Science, PubMed and Embase) were searched from inception date to May 31, 2020. Anti-inflammatory agents were defined as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, cytokine inhibitors, statins, pioglitazone, minocycline, N-acetylcysteine (NAC) and omega-3 fatty acid (Omega-3 FA). The main outcomes of this NMA were efficacy, acceptability and remission rate. Risk ratio (RR) was adopted for dichotomous outcomes, and the confidence interval (CI) was set at 95%. STATA 14.0 and R 3.6.3 were used to conduct the NMA. The study protocol was registered with PROSPERO (CRD42020182531).Results: A total of 39 studies, involving 2871 participants, were included in quantitative data synthesis. For efficacy, NSAIDs (RR=0.50, 95%CI: 0.26-0.73) and pioglitazone (RR=0.45, 95%CI: 0.20-0.84) were more favorable than placebo. With respect to acceptability, NSAIDs were more acceptable than placebo (RR=0.89, 95%CI: 0.77-0.99) and minocycline (RR=1.22, 95%CI: 1.03-1.49). For remission, NSAIDs were more superior than placebo (RR=0.48, 95%CI: 0.27-0.79) and Omega-3 FA (RR=2.01, 95%CI: 1.09-3.90), while NACs were more favorable than placebo (RR=0.39, 95%CI: 0.13-0.99). Based on the surface under the cumulative ranking curve (SUCRA) value, corticosteroids (0.86) were the best anti-inflammatory agent for MDD patients in terms of efficacy, but the head-to-head comparisons for the efficacy of glucocorticoids and other agents were not statistically significant. As for acceptability, NSAIDs (0.81) were much better than other anti-inflammatory agents. Besides, NAC (0.80) was the best anti-inflammatory agent in the terms of remission.Conclusions: In summary, we found that corticosteroids were more superior than other agents in terms of efficacy according to the SUCRA value. However, this result must be interpreted with caution because the head-to-head comparisons for the efficacy of glucocorticoids and other agents did not reach statistical significance. NSAIDs were recommended for acceptability and NAC for remission rate.

Microglia Loss and Astrocyte Activation Cause Dynamic Changes in Hippocampal [18F]DPA-714 Uptake in Mouse Models of Depression

“…We speculate that anti-inflammatory drugs used prior to microglia loss (within 1 week of stress) may prevent microglial reductions during the future course of the disease, thus reversing depression. The efficacy of anti-inflammatory drugs against depression has long been debated (Hang et al, 2021;Kloiber et al, 2021), and this controversy may partly be associated with alterations in the state of hippocampal microglia during depression. The use of anti-inflammatory drugs may improve depressive symptoms only when microglia are activated.…”

Current Perspectives on Pharmacological and Non-Pharmacological Interventions for the Inflammatory Mechanism of Unipolar Depression

“…Eventually, the results of a network meta-analysis imply that corticosteroids have a greater antidepressant capacity than other anti-inflammatory agents, but the head-to-head comparisons identified no statistically significant difference between these classes [ 71 ].…”

Montelukast induces beneficial behavioral outcomes and reduces inflammation in male and female rats

“…Inflammatory mediators (such as prostaglandin [PG] E2, interleukin [IL]-6, and tumor necrosis factor [TNF]-a), which regulate brain function, proliferation, differentiation, and survival of brain cells, have also shown interconnection to psychiatric disorders (5,14). To this end, pharmacotherapeutic strategies targeting neuroinflammatory components have been arduously explored in quest to further effective medicinal approaches to mental illness (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26); this pursuit is of particular pertinence given the untoward side-effects, low adherence rates and limited positive outcomes associated with most available psychiatric medications today (2, 27).…”