The use of cyclooxygenase-2 inhibitors in depression: a narrative review of the state of evidence


  • Alisha Abbas Department of Pharmacology, King George Medical University, Lucknow, Uttar Pradesh, India
  • Narendra Kumar Department of Pharmacology, King George Medical University, Lucknow, Uttar Pradesh, India
  • Reshma Choudhary Department of Pharmacology, King George Medical University, Lucknow, Uttar Pradesh, India



Depression, COX-2 inhibitors, Inflammation, Major depressive disorder, Celecoxib


Multiple lines of evidence suggest that inflammation contribute to the pathophysiology of depression. Various studies have found that patients with major depression have higher levels of pro-inflammatory cytokines like interleukin-1, interleukin-6, tumor necrosis factor-alpha and C-reactive protein. As a consequence of above findings this narrative literature review was done to look for the role of cyclooxygenase (COX)-2 inhibitors in the patients of depression. A web based search was done using the keywords like antidepressants, anti-inflammatory treatment, celecoxib, depression, neuro inflammation in well recognized databases like PubMed, Google scholar from the year 2006 to 2019 to come out with data that matches our inclusion criteria that have been pooled and critically analyzed. Although the exact mechanism remains to become elucidated the results suggest that COX-2 have beneficial role in treatment of depression and it may be used as an adjunct to the anti-depressant treatment as it may hasten the response to current treatment without any serious side effects.


Feltes KP, Doorduin J, Klein HC, Juárez-Orozco LE, Dierckx RA, Moriguchi-Jeckel CM, et al. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy. J Psychopharmacol. 2017;31(9):1149-65.

Hughes MM, Connor TJ, Harkin A. Stress-related immune markers in depression: implications for treatment. Int J Neuropsychopharmacol. 2016;19(6).

Rawdin BJ, Mellon SH, Dhabhar FS, Epel ES, Puterman E, Su Y, et al. Dysregulated relationship of inflammation and oxidative stress in major depression. Brain Behav Immun. 2013;31:143-52.

Smith RS. The macrophage theory of depression. Med Hypotheses. 1991;35(4):298-306.

Maes M, Bosmans E, De Jongh R, Kenis G, Vandoolaeghe E, Neels H. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine. 1997;9(11):853-8.

Dantzer R, Bluthe RM, Gheusi G, Cremona S, Laye S, Parnet P, et al. Molecular basis of sickness behavior. Ann New York Acad Sci. 1998;856(1):132-8.

Muller N, Riedel M, Schwarz MJ, Engel RR. Clinical effects of COX–2 inhibitors on cognition in schizophrenia. Europ Arch Psychiatr Clin Neurosci. 2005;255(2):149-51.

Sandrini M, Vitale G, Pini LA. Effect of rofecoxib on nociception and the serotonin system in the rat brain. Inflammation Res. 2002;51(3):154-9.

Myint AM, Kim YK, Verkerk R, Scharpe S, Steinbusch H, Leonard B. Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disorder. 2007;98(1):143-51.

Alamdarsaravi M, Ghajar A, Noorbala AA, Arbabi M, Emami A, Shahei F, et al. Efficacy and safety of celecoxib monotherapy for mild to moderate depression in patients with colorectal cancer: a randomized double-blind, placebo controlled trial. Psychiatr Res. 2017;255:59-65.

Mohammadinejad P, Arya P, Esfandbod M, Kaviani A, Najafi M, Kashani L, et al. Celecoxib versus diclofenac in mild to moderate depression management among breast cancer patients: A double-blind, placebo-controlled, randomized trial. Ann Pharmacotherap. 2015;49(9):953-61.

Jafari S, Ashrafizadeh SG, Zeinoddini A, Rasoulinejad M, Entezari P, Seddighi S, et al. Celecoxib for the treatment of mild‐to‐moderate depression due to acute brucellosis: a double‐blind, placebo‐controlled, randomized trial. J Clin Pharm Therapeut. 2015;40(4):441-6.

Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, et al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Molecular Psychiatr. 2006;11(7):680.

Akhondzadeh S, Jafari S, Raisi F, Nasehi AA, Ghoreishi A, Salehi B, et al. Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depression Anxiety. 2009;26(7):607-11.

Majd M, Hashemian F, Hosseini SM, Shariatpanahi MV, Sharifi A. A randomized, double-blind, placebo-controlled trial of celecoxib augmentation of sertraline in treatment of drug-naive depressed women: a pilot study. Iran J Pharmaceut Res. 2015;14(3):891.

Abbasi SH, Hosseini F, Modabbernia A, Ashrafi M, Akhondzadeh S. 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 Disorder. 2012;141(2-3):308-14.

Castillo MF, Murata S, Schwarz M, Schutze G, Moll N, Martin B, et al. Celecoxib augmentation of escitalopram in treatment-resistant bipolar depression and the effects on quinolinic acid. Neurol Psychiatr Brain Res. 2019;32:22-9.

Krause D, Myint AM, Schuett C, Musil R, Dehning S, Cerovecki A, et al. High kynurenine (a tryptophan metabolite) predicts remission in patients with major depression to add-on treatment with celecoxib. Frontiers Psychiatr. 2017;8:16.

Nery FG, Monkul ES, Hatch JP, Fonseca M, Zunta‐Soares GB, Frey BN, et al. Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double‐blind, randomized, placebo‐controlled study. Hum Psychopharmacol: Clin Exp. 2008;23(2):87-94.

Fourrier C, Sampson E, Mills NT, Baune BT. Anti-inflammatory treatment of depression: study protocol for a randomised controlled trial of vortioxetine augmented with celecoxib or placebo. Trials. 2018;19(1):447.

Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, et al. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proceedings Natl Acad Sci. 1994;91(25):12013-7.

Song C, Zhang XY, Manku M. Increased phospholipase A2 activity and inflammatory response but decreased nerve growth factor expression in the olfactory bulbectomized rat model of depression: effects of chronic ethyl-eicosapentaenoate treatment. J Neurosci. 2009;29(1):14-22.

Casolini P, Catalani A, Zuena AR, Angelucci L. Inhibition of COX‐2 reduces the age‐dependent increase of hippocampal inflammatory markers, corticosterone secretion, and behavioral impairments in the rat. J Neurosci Res. 2002;68(3):337-43.

Wohhleb ES, Hanke ML, Corona AW, Powell ND, La'Tonia MS, Bailey MT, et al. β-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat. J Neurosci. 2011;31(17):6277-88.

Xu C, Gu K, Yasen Y, Hou Y. Efficacy and safety of celecoxib therapy in osteoarthritis: a meta-analysis of randomized controlled trials. Med (Baltimore). 2016;95(20):e3585.




How to Cite

Abbas, A., Kumar, N., & Choudhary, R. (2019). The use of cyclooxygenase-2 inhibitors in depression: a narrative review of the state of evidence. International Journal of Basic & Clinical Pharmacology, 8(10), 2349–2353.



Review Articles