Comparison of inflammatory markers as moderators of depression outcomes: A CO-MED study

Background: Prior work suggests some individual immunomarkers may be useful moderators of treatment response between antidepressant medications. The relative moderating effect of individual immunomarkers remains unclear. It is also unknown whether combinations of immunomarkers have a superior moderating effect compared to any individual immunomarker. Methods: Baseline immunomarker levels were assayed using multiplex from a subset of participants in the CO-MED trial (n = 143). Individual and combinations of 19 immunomarkers were modeled as moderators between the three treatment arms (escitalopram monotherapy, escitalopram-bupropion and venlafaxine-mirtazapine) across a variety of depression outcomes. Results: Only IL-13 demonstrated a consistent moderating effect across all depression outcome measures. High IL-13 (>20 pg/ml) was associated with higher remission rates to bupropion-escitalopram (67%) versus escitalopram (24%) whereas low IL-13 was associated higher remission rates to escitalopram (59%) versus bupropion-escitalopram (38%). A similar, but weaker moderating effect was observed with venlafaxine-mirtazapine versus escitalopram. The addition of multiple immunomarkers did not consistently improve predictive modeling. Limitations: This is a secondary analysis of a single clinical trial with a relatively small sample size per treatment arm. The testing of specific individual and combinations of biomarkers was data-driven. Conclusions: Among 19 immunomarkers, Il-13 was the best single moderator of treatment outcome. Combinations of immunomarkers were not meaningfully superior to Il-13.