Marina Sagud1, Matea Nikolac Perkovic2, Bjanka Vuksan-Cusa1,3, Anja Maravic4, Dubravka Svob Strac2, Alma Mihaljevic Peles1, Maja Zivkovic4, Zorana Kusevic1, Nela Pivac5. 1. Department of Psychiatry, School of Medicine, Clinical Hospital Centre Zagreb, University of Zagreb, Zagreb, Croatia. 2. Rudjer Boskovic Institute, Division of Molecular Medicine, Bijenicka cesta 54, 10 000, Zagreb, Croatia. 3. Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia. 4. Clinics for Psychiatry Vrapce, Zagreb, Croatia. 5. Rudjer Boskovic Institute, Division of Molecular Medicine, Bijenicka cesta 54, 10 000, Zagreb, Croatia. npivac@irb.hr.
Abstract
BACKGROUND: Various antidepressants occupy brain serotonin transporter (SERT), decrease platelet serotonin (5-HT) concentration, and normalize reduced plasma brain-derived neurotrophic factor (BDNF) concentrations in depressed patients. Vortioxetine is a recently introduced antidepressant with a multimodal mechanism of action. In addition to SERT inhibition, vortioxetine acts via different 5-HT receptors. To further elucidate its mechanism of action, we have investigated the effects of vortioxetine on platelet 5-HT and plasma BDNF concentrations in patients with major depression. METHODS: Platelet 5-HT and plasma BDNF concentrations were determined in 44 healthy subjects at baseline and in 44 depressed patients before and after 4 weeks of treatment with vortioxetine (5-15 mg daily). Platelet 5-HT concentration was determined using the ortho-phthalaldehyde-enhanced fluorometric method, and plasma BDNF concentration using a commercial enzyme-linked immunosorbent assay (Quantikine ELISA, R&D Systems). RESULTS: At baseline, platelet 5-HT concentrations did not differ between depressed and control subjects, but plasma BDNF values were lower (p = 0.011; ω = 0.80) in depressed patients than in healthy subjects. Vortioxetine treatment significantly (p < 0.0001; ω = 0.80) decreased platelet 5-HT concentration and significantly (p = 0.004; ω = 0.80) increased plasma BDNF concentration in depressed patients compared to their baseline values. Age, gender, and smoking were not significantly associated with platelet 5-HT and plasma BDNF concentrations. CONCLUSION: Despite a novel mechanism of action, vortioxetine shares some common effects with other antidepressants. This study is the first to show that, in addition to clinical improvement, 4 weeks of treatment with vortioxetine (5-15 mg daily), decreased platelet 5-HT and increased plasma BDNF concentrations in depressed patients.
BACKGROUND: Various antidepressants occupy brain serotonin transporter (SERT), decrease platelet serotonin (5-HT) concentration, and normalize reduced plasma brain-derived neurotrophic factor (BDNF) concentrations in depressedpatients. Vortioxetine is a recently introduced antidepressant with a multimodal mechanism of action. In addition to SERT inhibition, vortioxetine acts via different 5-HT receptors. To further elucidate its mechanism of action, we have investigated the effects of vortioxetine on platelet 5-HT and plasma BDNF concentrations in patients with major depression. METHODS: Platelet 5-HT and plasma BDNF concentrations were determined in 44 healthy subjects at baseline and in 44 depressedpatients before and after 4 weeks of treatment with vortioxetine (5-15 mg daily). Platelet 5-HT concentration was determined using the ortho-phthalaldehyde-enhanced fluorometric method, and plasma BDNF concentration using a commercial enzyme-linked immunosorbent assay (Quantikine ELISA, R&D Systems). RESULTS: At baseline, platelet 5-HT concentrations did not differ between depressed and control subjects, but plasma BDNF values were lower (p = 0.011; ω = 0.80) in depressedpatients than in healthy subjects. Vortioxetine treatment significantly (p < 0.0001; ω = 0.80) decreased platelet 5-HT concentration and significantly (p = 0.004; ω = 0.80) increased plasma BDNF concentration in depressedpatients compared to their baseline values. Age, gender, and smoking were not significantly associated with platelet 5-HT and plasma BDNF concentrations. CONCLUSION: Despite a novel mechanism of action, vortioxetine shares some common effects with other antidepressants. This study is the first to show that, in addition to clinical improvement, 4 weeks of treatment with vortioxetine (5-15 mg daily), decreased platelet 5-HT and increased plasma BDNF concentrations in depressedpatients.
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