David Edberg1, Debra Hoppensteadt2, Amanda Walborn2, Jawed Fareed2, James Sinacore3, Angelos Halaris4. 1. Department of Psychiatry and Behavioral Neuroscience, Loyola University Stritch School of Medicine, Chicago, IL, USA. 2. Department of Pathology, Loyola University Stritch School of Medicine, Chicago, IL, USA. 3. Department of Public Health Sciences, Loyola University Stritch School of Medicine, Chicago, IL, USA. 4. Department of Psychiatry and Behavioral Neuroscience, Loyola University Stritch School of Medicine, Chicago, IL, USA. Electronic address: ahalaris@lumc.edu.
Abstract
BACKGROUND: Neuroinflammation plays a role in the pathophysiology of Bipolar Disorder Depression (BDD) and altered levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1, aka CCL2) have been reported. This study reports specifically on MCP-1 levels, as a potential marker of BDD and/or treatment response in patients receiving combination treatment with thecyclooxygenase-2 inhibitor, celecoxib (CBX). METHODS: In this randomized, 10-week, double-blind, two-arm, placebo-controlled study, 47 patients with treatment resistant BDD received eitherescitalopram (ESC) + CBX, or ESC + placebo (PBO). Plasma MCP-1 levels were measured at 3 time points in the BDD subjects, and in a healthy control (HC) group. Depression severity was quantified using the Hamilton Depression Scale (HAMD-17). RESULTS: The CBX group had significantly lower HAMD-17 scores vs. PBO at week 4 (P = 0.026) and week 8 (P = 0.002). MCP-1 levels were not significantly different in BDD vs. HC subjects at baseline (P = 0.588), nor in CBX vs. PBO groups at week 8 (P = 0.929). Week 8 HAMD-17 scores and MCP-1 levels were significantly negatively correlated in treatment non-responders to CBX or PBO (P = 0.050). Non-responders had significantly lower MCP-1 levels vs. responders at weeks 4 (P = 0.049) and 8 (P = 0.014). MCP-1 was positively correlated with pro-inflammatory analytes in the PBO group and with anti-inflammatory analytes in the CBX group. CONCLUSIONS: Combination treatment reduced treatment resistance and augmented antidepressant response. Baseline plasma MCP-1 levels were not altered in BDD patients. Since non-responders had lower levels of MCP-1, elevated MCP-1 may indicate a better response to CBX + SSRI treatment.
RCT Entities:
BACKGROUND: Neuroinflammation plays a role in the pathophysiology of Bipolar Disorder Depression (BDD) and altered levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1, aka CCL2) have been reported. This study reports specifically on MCP-1 levels, as a potential marker of BDD and/or treatment response in patients receiving combination treatment with the cyclooxygenase-2 inhibitor, celecoxib (CBX). METHODS: In this randomized, 10-week, double-blind, two-arm, placebo-controlled study, 47 patients with treatment resistant BDD received either escitalopram (ESC) + CBX, or ESC + placebo (PBO). Plasma MCP-1 levels were measured at 3 time points in the BDD subjects, and in a healthy control (HC) group. Depression severity was quantified using the Hamilton Depression Scale (HAMD-17). RESULTS: The CBX group had significantly lower HAMD-17 scores vs. PBO at week 4 (P = 0.026) and week 8 (P = 0.002). MCP-1 levels were not significantly different in BDD vs. HC subjects at baseline (P = 0.588), nor in CBX vs. PBO groups at week 8 (P = 0.929). Week 8 HAMD-17 scores and MCP-1 levels were significantly negatively correlated in treatment non-responders to CBX or PBO (P = 0.050). Non-responders had significantly lower MCP-1 levels vs. responders at weeks 4 (P = 0.049) and 8 (P = 0.014). MCP-1 was positively correlated with pro-inflammatory analytes in the PBO group and with anti-inflammatory analytes in the CBX group. CONCLUSIONS: Combination treatment reduced treatment resistance and augmented antidepressant response. Baseline plasma MCP-1 levels were not altered in BDD patients. Since non-responders had lower levels of MCP-1, elevated MCP-1 may indicate a better response to CBX + SSRI treatment.