Modulation of the inflammatory response benefits treatment-resistant bipolar depression: A randomized clinical trial

J Affect Disord. 2020 Jan 15;261:145-152. doi: 10.1016/j.jad.2019.10.021. Epub 2019 Oct 13.


Objective: The goal of this study was to reduce treatment resistance and enhance antidepressant response in patients with treatment-resistant bipolar depression (TRBDD) by modulating inflammatory activation.

Methods: Forty-seven TRBDD patients completed a randomized, double-blind, placebo (PBO)-controlled two-arm study using celecoxib (CBX), a cyclooxygenase 2 (COX-2) inhibitor, in combination with escitalopram (ESC). The Hamilton Depression (17-Item) and the Hamilton Anxiety Rating Scales were used to quantify symptom severity. Self-rating instruments included BDI, BAI and QLES-Q questioner. An adverse events inventory was used, and the possibility of bleeding diathesis was monitored. Complete blood count (CBC), prothrombin time (PT), and activated partial thromboplastin time (APTT) were determined. Comparison of mood scores between the CBX and PBO groups were conducted using a mixed ANOVA and an Independent Sample Student t-test.

Results: The CBX adjunctive treatment produced significantly more responders and remitters than the PBO arm. Compared to the PBO group (n = 20), the CBX group (n = 27) experienced lower depression severity through the entire course of the study, showing significant decrease in depression and anxiety scores as early as week 1. Except for initial mild nausea, no adverse events were reported and study medications were well tolerated.

Conclusions: Modulation of the inflammatory response through targeted inhibition of the enzyme COX-2 by means of CBX reduces TRBDD and augments and accelerates treatment response in an efficacious and safe manner. Future studies should replicate these findings and additionally investigate whether prolonged administration of CBX is required to maintain remission by adding a discontinuation phase to the study design.

Trial registration: ID: NCT01479829.

Keywords: Bipolar disorder; Celecoxib; Escitalopram; Inflammation; Treatment resistance.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antidepressive Agents / therapeutic use
  • Bipolar Disorder / drug therapy*
  • Celecoxib / administration & dosage
  • Celecoxib / therapeutic use*
  • Citalopram / therapeutic use
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antidepressive Agents
  • Cyclooxygenase 2 Inhibitors
  • Citalopram
  • Celecoxib

Associated data