Comparative effect of vortioxetine and sertraline on clinical and inflammatory profile in Parkinson’s disease with comorbid depression

Background: Preclinical and clinical studies suggest that the multimodal antidepressant vortioxetine may offer a valuable therapeutic option in the treatment of depression associated with neurological disorders, including Parkinson's disease (PD). Objectives: To compare the effect of vortioxetine and the SSRI sertraline in the treatment of PD and comorbid depression, placing emphasis on peripheral inflammation markers. Methods: This is an observational longitudinal study. We have recruited 33 patients affected by PD with comorbid depression, evaluated for motor and non-motor symptoms, depression, and peripheral and soluble markers of inflammation at baseline and at the end of antidepressant treatment. Patients were divided into two groups treated with either vortioxetine (10-20 mg/day) or sertraline (50 mg/day) for 4 months. A group of 12 healthy controls was also used for comparative purposes. Results: At baseline PD patients showed a higher number of "classical" monocytes and a lower number of "non-classical" monocytes and myeloid dendritic cells (mDCs). The number and activity of DCs generated from isolated monocytes were also lower in PD patients. While both sertraline and vortioxetine treatment further reduced the number of mDCs, only vortioxetine had a restorative effect on CD40- and CD54-expressing DCs and their function. Both drugs display an antidepressant activity, but vortioxetine was superior to sertraline in improving cognitive function, anxiety, anhedonia, and apathy. Conclusion: These data evaluate for the first time the immunomodulatory effects of two different treatments in PD patients with comorbid depression, highlighting the greater immunomodulatory capacity of vortioxetine.