Combined effect of antidepressant and anti-inflammatory drugs in an animal model of depressio

The delay in the onset of action of antidepressants remains one of the unsolved issues in the treatment of depression despite the availability of safe and effective drugs. It has been known for years that depression may share identical symptoms as those in inflammatory reaction and that immune function and inflammation markers are altered in psychiatric patients. This suggests to use anti-inflammatory drugs as an adjunctive therapy for depression. We previously demonstrated that the combination of acetylsalicylic acid (ASA) with Fluoxetine (FLX) accelerated and potentiated the effect of the antidepressant in the chronic escape model of depression (Brunello et al., 2006). These results, together with preliminary clinical data in major depressed nonresponder patients, suggest that ASA might accelerate the onset of action of SSRIs (Mendlewicz et al., 2006). Preclinical and clinical studies have recently reported that Escitalopram (ESC), the active enantiomer of citalopram, shows a faster onset of action compared to other antidepressants. The aim of our study was to compare the effect of one week of combined treatment with ESC plus ASA vs. ESC alone in the chronic escape deficit model of depression. Significant response after one week of treatment was present in about 50% of the animals receiving ESC (10 mg/kg/day) alone and in about 75% of the rats receiving ESC plus ASA (45 mg/kg/day). These results suggest that the co-administration of ASA with ESC increased the response to treatment in reverting the behavioural despair induced by stress in rats, thus confirming the specific effect of combined therapy.