Objectives: A growing body of evidence strongly suggests that inşammatory process and immune responses are involved in the pathophysiology of depression. While depression itself is considered a heterogeneous disorder, the involvement of immune system further complicates the matter. Meanwhile, several antidepressant medications (e.g. şuoxetine) have been reported to exert immunomodulatory properties, which may affect human immune system and may partly contribute to their efficacy. Moreover, it must be noted that immune response/system profoundly varies between the genders due to differences in sex hormones. However, there have been no controlled studies investigating the benefits of celecoxib augmentation therapy in treatment-naïve women with depression. To increase the homogeneity of the study population, the present study was designed to examine the antidepressant effects of celecoxib augmentation of sertraline in the treatment of female drug-naïve patients with depression for 8 weeks.
Methods: Forty female patients diagnosed with first episode of major depression according to DSM-IV-TR criteria were recruited for this study. The inclusion criteria were: 1. First episode of major depression, 2. Female gender, 3. Antidepressant-naïve, 4. Age between 18 and 50 years, and 5. Hamilton depression rating scale (17 items) score ranging from 18 to 36. The patients with history of other psychiatric disorders, significant suicidal ideation, liver and kidney dysfunction, and cardiovascular disorders were excluded. The patients were randomly assigned into two equal groups receiving either sertraline 50-100 mg/day plus celecoxib 100 mg twice daily or sertraline 50-100 mg/day plus placebo twice daily. The participants were assessed by Hamilton depression and anxiety rating scale at baseline, and 4th and 8th weeks of the treatment. The data were analyzed by Mann-Whitney U test and Fisher's exact test. The trial was registered in Iranian Registry of Clinical Trials (IRCT registration number: IRCT201009043106N3). This study was approved by Azad University Pharmaceutical Sciences Ethics Committee (No: 4114).
Results: No significant differences were observed between two groups regarding demographicals characteristics and the Hamilton depression score at baseline. The mean Hamilton depression score decreased from 26.14 (SD=5.51) at baseline to 12.42 (SD=5) at 4th week and from 26.22 (SD=5.38) at baseline to 17.33 (SD=5.24) at 4th week in the celecoxib and placebo groups, respectively. Celecoxib group showed significantly greater decrease in Hamilton scores compared to placebo (P< 0.05) at the end of week 4. The mean decrease in Hamilton score was greater in the treatment group compared to placebo over 8 weeks, although it was not statistically significant. In addition, remission rate (HamD scores <= 7) was significantly higher in the celecoxib group compared to placebo group (57% and 11% respectively, P<0.05).
Conclusion: It can be suggested that celecoxib augmentation therapy may accelerate the onset of therapeutic action of sertraline and also result in higher remission rate at the endpoint of treatment. The results of present study substantiate the hypothesis that add-on treatment with anti-inşammatory agents can be beneficial in the management of depression.