Efficacy of infliximab in treatment-resistant depression: A systematic review and meta-analysis

Background: Treatment-resistant depression (TRD) denotes the therapeutic failure of at least two evidence-based, dose-based, and time-appropriate treatment regiments for major depressive disorder (MDD). Studies have suggested that alterations in proinflammatory cytokines play an important role in the pathophysiology of TRD, as well as a significant relationship between the number of failed treatment and the levels of tumor necrosis factor-alpha (TNF-alpha). Objective: Performed a systematic review and meta-analysis to evaluate the potential effect of the TNF-inhibitor Infliximab adjunct treatment in MDD, through randomized controlled trials (RCT). Methods: A search in the electronic databases was proceeded, on MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, Web of Science, IBECS, LILACS, PsycINFO, Congress Abstracts, and Grey literature (Google Scholar and the British Library) for studies published until April 2019. A search strategy was developed using the terms: "Mood disorder" OR "Depressive Disorder" OR "Bipolar disorder" AND "Infliximab" OR "tumor necrosis factor antagonist" as text words and Medical Subject Headings (i.e., MeSH and EMTREE). The therapeutic effects of adjunctive treatment with Infliximab were analyzed. The meta-analysis was performed including the results of the Hamilton Scale for Depression (HAM-D). Results: Four primary studies were included in the systematic review, with a total of 152 patients. The meta-analysis did not show a statistically significant effect of Infliximab as an adjuvant treatment for TRD. Limitations: Articles in this meta-analysis originate from the same country. The main treatments used were different among the included studies. Conclusion: Infliximab was not efficient in reducing depressive symptoms according to the HAM-D, only when the patients already had increased inflammatory genes, including TNF and C-reactive protein (CRP).