Pro-inflammatory markers are associated with response to sequential pharmacotherapy in major depressive disorder: A CAN-BIND-1 report

Objective: There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD). Methods: In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10- 20 mg daily for 8 weeks. Responders continued escitalopram while non-responders received adjunctive aripiprazole 2-10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers - C-reactive protein, Interleukin (IL)-1β, IL-6, IL-17, Interferon gamma (IFN)-G, Tumour Necrosis Factor (TNF)-a, and Chemokine C-C motif ligand-2 (CCL-2) - measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyses to assess associations between inflammatory markers and treatment response. Results: Pre-treatment IFN-G and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. 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. Conclusion: Higher pre-treatment levels of IFN-G 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.