Effects of celecoxib augmentation of antidepressant or anxiolytic treatment on affective symptoms and inflammatory markers in patients with anxiety disorders: exploratory study

Abstract

Prolonged stress has been associated with elevated levels of circulating proinflammatory cytokines. Cyclo-oxygenase-2 inhibitors such as celecoxib exert anti-inflammatory effects and may enhance the response to antidepressant drug treatment in patients with depressive disorders, but their effect on anxiety symptoms in patients with anxiety disorders is uncertain. Patients with a primary diagnosis of an anxiety disorder, with stabilised symptoms, underwent either 6 weeks of celecoxib augmentation of continued treatment (n = 18) or continued 'treatment as usual' (n = 9). Assessments included the Warwick-Edinburgh mental well-being Scale (WEMWEBS), Hospital Anxiety and Depression Scale (HADS), Oxford questionnaire of emotional side effects of antidepressants (OQUESA) and Clinical Global Impression of Illness Severity (CGI-S). Venous blood samples were collected for assays of inflammatory cytokines. Patients who underwent celecoxib augmentation showed significant reductions in anxiety (HADS-A −3.17) and depressive (HADS-D −2.11) symptoms and in overall illness severity (CGI-S −1.11), and improvements in mental well-being (WEMWBS 7.5) and positive changes in emotional responsiveness (OQUESA-RP −3.56; OQUESA-AC −4.22): these were not seen with 'treatment as usual'. There were no significant changes in blood levels of inflammatory cytokines in either group. Celecoxib augmentation appeared associated with beneficial effects on anxiety and depressive symptoms and mental well-being. The findings from this pilot study merit further exploration within a double-blind, randomised placebo-controlled study.

Selective COX-2 Inhibitors: Road from Success to Controversy and the Quest for Repurposing

“…A meta-analysis of randomized clinical trials reported celecoxib to decrease depressive symptoms with reduced adverse effects; however, the mean estimate was claimed to be uncertain due to a high risk of bias and heterogeneity [ 71 ]. An exploratory study revealed that celecoxib augmentation of anxiolytic or antidepressant drugs exhibits positive effects on anxiety, depression, and mental well-being [ 72 ]. In contrast to these findings, recently published data of a placebo-controlled, double-blind, randomized trial reported that celecoxib augmentation of vortioxetine has no evidence of superior efficacy as compared to a placebo in mitigating depressive severity [ 73 ].…”

Biology of cyclooxygenase-2: An application in depression therapeutics

“…Cyclo-oxygen-ase-2 (COX-2) can regulate the occurrence and development of depression. In recent years, COX-2 inhibitors have been widely used in the treatment of depressed patients, and the drugs commonly used in clinical practice as COX-2 inhibitors are non-steroidal anti-inflammatory drugs (NSAIDs), all of which have varying degrees of efficacy in depression (111)(112)(113). Some natural compounds such 10.3389/fpsyt.2022.1037588 as xanthines, alkaloids, astragals, flavonoids, terpenoids and quinones also have the ability to inhibit COX-2 activity.…”

Clinical Utility of Fluid Biomarker in Depressive Disorder

“…Inflammatory biomarkers are an interesting area of investigation, given the known involvement of inflammation factors in the pathophysiology of depression [ 44 ], and a number of possible biomarkers are currently under investigation for diagnosis, outcome prediction, staging, and stratification of interventions [ 45 - 48 ]. However, at present there are no approved inflammatory biomarkers for use in routine clinical practice.…”