Celecoxib augmentation of escitalopram in treatment-resistant bipolar depression and the effects on Quinolinic Acid

Objectives

Treatment-resistance is high in bipolar disorder and is associated with a pro-inflammatory state and diversion of tryptophan toward the kynurenine pathway. This study as part of a large clinical trial, sought to determine, if modulation of the inflammatory response by inhibiting cyclooxygenase-2 (COX-2) with celecoxib combined with escitalopram, would convert treatment-resistant bipolar depression to response or remission and whether blood levels of quinolinic acid (QA) differ from healthy controls and change with treatment response.

Methods

This was a randomized, double-blind, two-arm, placebo-controlled study. Subjects who met study criteria were randomized to receive escitalopram + celecoxib, or escitalopram + placebo. Inflammation biomarkers and kynurenine pathway intermediates were determined at baseline and weeks 4 and 8.

Results

Patients receiving the celecoxib combination showed improved response and higher remission rate. All patients had significantly lower QA levels at baseline compared to healthy controls. QA values did not change significantly over time, but a downtrend was noted through treatment. Responders had marginally lower QA values than non-responders. Factors that might have led to low QA levels may include prior exposure to a variety of psychoactive agents.

Conclusions

Although QA did not significantly change, symptom reduction and remission occurred more frequently in the celecoxib group, demonstrating the beneficial effect of inflammation modulation.