, Volume 233, Issue 17, pp 3259–3267 | Cite as

A prospective, longitudinal study of platelet serotonin and plasma brain-derived neurotrophic factor concentrations in major depression: effects of vortioxetine treatment

  • Marina Sagud
  • Matea Nikolac Perkovic
  • Bjanka Vuksan-Cusa
  • Anja Maravic
  • Dubravka Svob Strac
  • Alma Mihaljevic Peles
  • Maja Zivkovic
  • Zorana Kusevic
  • Nela Pivac
Original Investigation



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.


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).


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.


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.


Antidepressants Depression Plasma BDNF Platelet serotonin Vortioxetine 



This study was supported by the University of Zagreb, Project Code: BM126, and the Croatian Psychiatric Association. The authors thank Marin Kirigin, MD, for editing the English language.

Compliance with ethical standards

Study procedures were approved by the local Ethics Committees. Informed consent was obtained from all participants. All procedures were in accordance with the ethical standards laid out in Helsinki Declaration of 1975 (as revised in 1983).

Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Marina Sagud
    • 1
  • Matea Nikolac Perkovic
    • 2
  • Bjanka Vuksan-Cusa
    • 1
    • 3
  • Anja Maravic
    • 4
  • Dubravka Svob Strac
    • 2
  • Alma Mihaljevic Peles
    • 1
  • Maja Zivkovic
    • 4
  • Zorana Kusevic
    • 1
  • Nela Pivac
    • 2
  1. 1.Department of Psychiatry, School of Medicine, Clinical Hospital Centre ZagrebUniversity of ZagrebZagrebCroatia
  2. 2.Rudjer Boskovic Institute, Division of Molecular MedicineZagrebCroatia
  3. 3.Faculty of MedicineJosip Juraj Strossmayer University of OsijekOsijekCroatia
  4. 4.Clinics for Psychiatry VrapceZagrebCroatia

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