Interleukin-6 Levels and Response to Selective Serotonin Reuptake Inhibitor Treatment in Major Depressive Disorder in a Tertiary Care Center

Abstract Background: The inflammatory hypothesis for major depressive disorder (MDD) proposes the role of systemic and neuroinflammation in its pathogenesis. Interleukin-6 (IL-6) is promising as a biomarker for MDD, and prior research warrants further investigation of its role, especially concerning the treatment and prognosis of MDD. Aim: Accordingly, our objective was to assess IL-6 levels in MDD, study changes in IL-6 with selective serotonin reuptake inhibitor (SSRI) treatment, and correlate response/nonresponse to treatment with IL-6 levels. Materials and Methods: We enrolled 40 patients diagnosed with MDD (new onset/off medications since ≥9 months). Patients were prescribed an SSRI (escitalopram/sertraline/fluoxetine) and assessed over three visits – initial, 15 days, and 6 weeks. IL-6 and depression severity (using a 17-item Hamilton Depression Rating Scale – [HAMD-17]) were recorded at baseline and 6 weeks. Results: The mean IL-6 levels ( n = 40) were elevated at baseline, with levels significantly higher in males. In patients completing all follow-ups ( n = 24), IL-6 levels decreased at 6 weeks, with sertraline causing the highest decrease. Responders to treatment recorded lower baseline levels, and a greater, significant reduction in IL-6 compared to nonresponders. For predicting response, baseline IL-6 and HAMD-17 showed high positive and low negative predictive values, though statistically nonsignificant. Conclusion: Our study findings indicate high baseline inflammation (IL-6) in MDD, which decreases with SSRI treatment at 6 weeks. Sertraline has the highest anti-inflammatory activity. Response to treatment is correlated with a significant reduction in IL-6. These findings highlight the role of inflammation, particularly IL-6, in the genesis, treatment, and prognosis of depression, and reveal interesting trends for response prediction using baseline IL-6.