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

Abstract

Signs of an inflammatory process, in particular increased pro-inflammatory cytokines and increased levels of prostaglandine E 2 (PGE 2 ), have repeatedly been described in major depression (MD). As cyclooxygenase-2 (COX-2) inhibitors inhibit the PGE 2 production and the production of pro-inflammatory cytokines, we performed a therapeutic trial with the COX-2 inhibitor celecoxib. In a prospective, double-blind, add-on study, 40 patients suffering from an acute depressive episode were randomly assigned to either reboxetine and celecoxib or to reboxetine plus placebo. After a wash-out period, 20 patients received 4-10 mg reboxetine plus placebo and 20 received reboxetine plus 400 mg celecoxib for 6 weeks. The treatment effect was calculated by analysis of variance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or reboxetine dose or plasma levels. Over 6 weeks, both groups of patients showed significant improvement in scores of the Hamilton Depression Scale. However, the celecoxib group showed significantly greater improvement compared to the reboxetine-alone group. Additional treatment with celecoxib has significant positive effects on the therapeutic action of reboxetine with regard to depressive symptomatology. Moreover, the fact that treatment with an anti-inflammatory drug showed beneficial effects on MD indicates that inflammation is related to the pathomechanism of the disorder, although the exact mechanisms remain to become elucidated.

Low tumor necrosis factor‐α levels predict symptom reduction during electroconvulsive therapy in major depressive disorder

“…Elevated TNFα levels have also been associated with suicide attempts and dissociative symptoms (Abbasi, Hosseini, Modabbernia, Ashrafi, & Akhondzadeh, 2012; Bizik et al., 2014). The nonsteroidal anti‐inflammatory drug celecoxib reportedly has a beneficial effect in patients with MDD as an adjuvant medication (Akhondzadeh et al., 2009; Kargar et al., 2014; Müller et al., 2006). Additionally, celecoxib reduced the TNFα level after an ECT series in patients with bipolar disorder (Dantzer, O'Connor, Lawson, & Kelley, 2011).…”

Influence of COX-2 and OXTR polymorphisms on treatment outcome in treatment resistant depression

“…The selection of SNPs under investigation was based on previous research suggesting a possible association between COX-2 (rs5275 and rs20417) and OXTR (rs53576 and rs2254298) genes and antidepressant treatment [10,20].…”

“…While the use of COX-2 inhibitors in association with reboxetine was found to increase symptomatological improvement in MDD patients [20], contrasting results have been reported regarding the potential role of OXT in depression [6,8,22,24,29]. This nonapeptide hormone has however been found to attenuate the stress response in both rats and humans [15].…”

“…An interesting inflammatory signaling pathway is the phospholipase/cyclooxygenase (COX)/prostaglandin (PGE) pathway. Indeed, increased pro-inflammatory cytokines and increased levels of PGE(2) have repeatedly been described in MDD [20]. COX-2 is 0304-3940/$ -see front matter © 2012 Elsevier Ireland Ltd. All rights reserved.…”

“…Furthermore, COX-2 can be induced in microglia and astrocytes in a variety of pathological conditions including hypoxia and excitotoxins [16]. Interestingly, COX-2 inhibitors, that inhibit the PGE(2) production, were recently found to increase reboxetine effects in MDD patients [20]. Another interesting protein that appears to be involved in inflammatory processes is oxytocin (OXT) [1].…”