Effect of celecoxib add-on treatment on symptoms and serum IL-6 concentrations in patients with major depressive disorder: randomized double-blind placebo-controlled study

J Affect Disord. 2012 Dec 10;141(2-3):308-14. doi: 10.1016/j.jad.2012.03.033. Epub 2012 Apr 18.


Background: It has been proposed that the mechanism of the antidepressant effect of celecoxib is linked to its anti-inflammatory action and particularly its inhibitory effect on pro-inflammatory cytokines (e.g. interleukin-6(IL-6)). We measured changes in serum IL-6 concentrations and depressive symptoms following administration of celecoxib in patients with major depressive disorder (MDD).

Methods: In a randomized double-blind placebo-controlled study, 40 patients with MDD and Hamilton Depression Rating Scale-17 items (Ham-D) score ≥18 were randomly assigned to either celecoxib (200mg twice daily) or placebo in addition to sertraline (200mg/day) for 6 weeks. Outcome measures were serum IL-6 concentrations at baseline and week 6, and Ham-D scores at baseline and weeks 1, 2, 4, and 6.

Results: The celecoxib group showed significantly greater reduction in serum IL-6 concentrations (mean difference (95%CI)=0.42(0.30 to 0.55) pg/ml, t(35)=6.727, P<0.001) as well as Ham-D scores (mean difference (95%CI)=3.35(1.08 to 5.61), t(38)=2.99, P=0.005) than the placebo group. The patients in the celecoxib group experienced more response (95%) and remission (35%) than the placebo group (50% and 5%, P=0.003 and 0.04 respectively). Baseline serum IL-6 levels were significantly correlated with baseline Ham-D scores (r=0.378, P=0.016). Significant correlation was observed between reduction of Ham-D scores and reduction of serum IL-6 levels at week 6 (r=0.673, P<0.001).

Limitations: We did not measure other inflammatory biomarkers.

Conclusions: We showed that the antidepressant activity of celecoxib might be linked to its capability of reducing IL-6 concentrations. Moreover, supporting previous studies we showed that celecoxib is both safe and effective as an adjunctive antidepressant (Registration number: IRCT138903124090N1).

Publication types

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

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / therapeutic use*
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Biomarkers / blood
  • Celecoxib
  • Depressive Disorder, Major / blood
  • Depressive Disorder, Major / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Pyrazoles / administration & dosage
  • Pyrazoles / therapeutic use*
  • Sertraline / therapeutic use
  • Sulfonamides / administration & dosage
  • Sulfonamides / therapeutic use*


  • Antidepressive Agents
  • Biomarkers
  • Interleukin-6
  • Pyrazoles
  • Sulfonamides
  • Celecoxib
  • Sertraline