Experimental Research on the Interactions between Selective COX-2 Inhibitors and Antidepressants

Several studies have suggested an association between depression and inflammation (reviewed in 1, 2, 3, 4). Treatment with pro-inflammatory agents (Calmette-Guerin bacillus, endotoxins) causes depressive symptoms (5, 6, 7). Non-steroidal antiinflammatory agents, NSAIDs, particularly the COX-2 selective ones (e.g., celecoxib) showed promising results in the augmentation of the antidepressant effect in clinical studies on major depression or depressive symptomatology. The antidepressant activity of celecoxib was apparent both in the assessment of the frequency of the remissions, and in the assessment of the therapeutic response (reviewed in 8). Contrary to these studies, there is evidence that NSAIDs decrease the antidepressant effects of the antidepressant drugs. Certain NSAIDs showed depressant effects in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) clinical trial (concomitant administration of NSAIDs and antidepressants was shown to decrease the responder percentage to 45% in major depression, vs. 55% responder percentage when antidepressants were given without NSAIDs) (9). There is experimental evidence of antidepressant effects of NSAIDs in laboratory animals, particularly mice and rats, but also two studies showing that certain NSAIDs have depressant activity when given alone or in association with serotonin-specific reuptake inhibitors, SSRI (9, 10, 11, 12).