Psy-World

Cortisol and cytokine levels are only partially normalised after long term treatment with SSRIs in major depressive disorder.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis function is a common feature in major depressive disorder with hypercortisolism and variations in pro-inflammatory cytokine levels. In previous studies the effects of antidepressant therapy on the altered regulation of the neuroendocrine and immune systems have been evaluated over short periods of time varying from minutes to 16 weeks. A recent study measured changes in cortisol and cytokine levels during a chronic treatment for one year with selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder (MDD). Thirty one patients diagnosed with MDD were administered SSRI (19 fluoxetine, 7 paroxetine, 5 sertraline) for 52 weeks. Patients were evaluated monthly using the 21-items Hamilton Depression Scale (HDRS). Blood and urine samples were taken from patients at baseline and week (W) 5, 20, 36, and 52 of antidepressant treatment for determination of levels of interleukin IL-1beta, IL-10, IL-2, IFN-gamma, IL-4, IL-13, and 24-h urine cortisol. At baseline, the mean HDRS score was 20.28 ± 2.07. Clinical remission, with a mean HDRS score of 2.57 ± 3.8, was reached at W20 and was maintained until the end of the study. Baseline levels of cortisol, IL-4, IL-13 (Th2) and IL-10 were higher in MDD patients than in healthy volunteers. At W20 the levels of IL-2 and IL-1beta increased but without changes in cortisol. At W52 cortisol levels were significantly reduced (p < 0.01), levels of IL-1beta and IFN-gamma were increased and those of Th2 cytokines were decreased. These results suggest that the use of SSRIs for more than a year (maintenance phase) is justified for a full restoration of the HPA axis function, which might be involved in the reduction of the incidence of relapsing periods of depression. Hernández ME, Mendieta D, Martínez-Fong D, Loría F, Moreno J, Estrada I, Bojalil R, Pavón L (2008). Variations in circulating cytokine levels during 52 week course of treatment with SSRI for major depressive disorder. Eur Neuropsychopharmacol 18:917-924. Updated November 2008