Predictive Role of Inflammatory Biomarkers in Electroconvulsive Therapy Response Among Patients With Major Depressive Disorder: A Systematic Review.

Abstract

Major depressive disorder (MDD) is a highly prevalent and disabling psychiatric condition associated with substantial morbidity and mortality. Although its pathophysiology remains incompletely understood, converging evidence implicates immune dysregulation and inflammatory mechanisms in its development. Electroconvulsive therapy (ECT) remains the most effective intervention for treatment-resistant depression; however, no validated biomarkers currently predict therapeutic response. This systematic review synthesizes current findings on the potential predictive value of inflammatory and immunologic biomarkers-particularly interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP)-for ECT outcomes in patients with MDD. A comprehensive literature search was conducted across PubMed, EMBASE, Cochrane, and PsycINFO without language or date restrictions, including adult patients (18 years or older) with MDD who received ECT and reported at least one target biomarker and a validated clinical outcome measure. Fifteen studies met the inclusion criteria, with IL-6, TNF-α, and CRP being the most frequently investigated markers. Several studies suggested that elevated baseline IL-6 and moderately increased CRP levels may predict a more favorable ECT response-particularly among women-yet findings were largely inconsistent, and no robust biomarker emerged as a reliable predictor. Overall, the evidence remains insufficient to establish interleukins or CRP as dependable predictors of antidepressant response to ECT in MDD. Substantial heterogeneity in methodology, small sample sizes, and variability in biomarker assays highlight the need for large-scale, standardized, longitudinal studies.