Abstract

There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD). In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10-20mg daily for 8weeks. Responders continued escitalopram while non-responders received adjunctive aripiprazole 2-10mg daily for 8weeks. Plasma levels of pro-inflammatory markers-C-reactive protein, interleukin (IL)-1β, IL-6, IL-17, interferon-gamma (IFN)-Γ, tumor necrosis factor (TNF)-α, and Chemokine C-C motif ligand-2 (CCL-2)-measured at baseline, and after 2, 8 and 16weeks were included in logistic regression analyzes to assess associations between inflammatory markers and treatment response. Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16. Higher pre-treatment levels of IFN-Γ and CCL-2 were associated with non-response to escitalopram. Increasing levels of these pro-inflammatory markers may be associated with non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.

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