Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial

Abstract

Background: The pathophysiology of depression is associated with the hyperactivity of immune inflammatory responses. Cyclooxygenase-2 inhibitors such as celecoxib reduce the production of pro-inflammatory cytokines. The purpose of the present investigation was to assess the efficacy of celecoxib as an adjuvant agent in the treatment of major depression in a six-week double blind and placebo controlled trial. Methods: Forty adult outpatients who met the DSM-IV-TR criteria for major depression participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. Patients were allocated in a random fashion: 20 to fluoxetine 40 mg/day plus celecoxib 400 mg/day (200 mg bid) (morning and evening) and 20 to fluoxetine 40 mg/ day plus placebo. Patients were assessed by a psychiatrist at baseline and after 1, 2, 4, and 6 weeks after the medication started. Results: Although both protocols significantly decreased the score of Hamilton Rating Scale for Depression over the trial period, the combination of fluoxetine and celecoxib showed a significant superiority over fluoxetine alone in the treatment of symptoms of major depression. There were no significant differences in the two groups in terms of observed side effects. Conclusion: The results of this study suggest that celecoxib may be an effective adjuvant agent in the management of patients with major depression and anti-inflammatory therapies should be further investigated.

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

“…Of the 4 remaining trials, all were small (~n = 20 per group) and all used celecoxib versus placebo as an add-on to a conventional antidepressant in patients with major depression. The 4 studies showed a positive benefit for celecoxib at some point in the trial, although the one study conducted in Germany was plagued by a dropout rate of 50% in the celecoxib group and 60% in the placebo group (Muller et al, 2006), and of the remaining 3 studies, all of which were conducted in Iran, one showed no effect at 8 weeks (Hashemian et al, 2011); yet, for unclear reasons, in each meta-analysis, the more positive 4-week data from this study (that appear in the literature as an abstract) are included in the efficacy evaluation (Muller et al, 2006;Akhondzadeh et al, 2009;Hashemian et al, 2011;Abbasi et al, 2012). Of note, the Iranian group has also published positive data for celecoxib in OCD, acute bipolar mania, and depression in breast cancer, indicating an extraordinary efficacy that warrants further evaluation (Arabzadeh et al, 2015;Mohammadinejad et al, 2015;Shalbafan et al, 2015).…”

Antidepressant Augmentation With Anti-Inflammatory Agents

“…These authors searched electronic databases, reference lists, and other sources and identified 5 placebo-controlled RCTs of celecoxib for the treatment of unipolar (4 RCTs) or bipolar (1 RCT) depression in adults. Only data from the 4 unipolar depression RCTs [13][14][15][16] were included in the metaanalysis; one 15 of these 4 RCTs had not been published as a full paper. Three studies were conducted in Iran, [14][15][16] and 1, in Germany.…”

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).…”