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

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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.

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Acknowledgments

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.

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    Authors and Affiliations

    1. Department of Psychiatry, School of Medicine, Clinical Hospital Centre Zagreb, University of Zagreb, Zagreb, Croatia

      Marina Sagud, Bjanka Vuksan-Cusa, Alma Mihaljevic Peles & Zorana Kusevic

    2. Rudjer Boskovic Institute, Division of Molecular Medicine, Bijenicka cesta 54, 10 000, Zagreb, Croatia

      Matea Nikolac Perkovic, Dubravka Svob Strac & Nela Pivac

    3. Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia

      Bjanka Vuksan-Cusa

    4. Clinics for Psychiatry Vrapce, Zagreb, Croatia

      Anja Maravic & Maja Zivkovic

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    1. Marina Sagud
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    2. Matea Nikolac Perkovic
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    6. Alma Mihaljevic Peles
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    9. Nela Pivac
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    Corresponding author

    Correspondence to Nela Pivac.

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    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).

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    The authors declare that they have no conflicts of interest.

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    Marina Sagud and Matea Nikolac Perkovic contributed equally to this work.

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    Sagud, M., Nikolac Perkovic, M., Vuksan-Cusa, B. et al. A prospective, longitudinal study of platelet serotonin and plasma brain-derived neurotrophic factor concentrations in major depression: effects of vortioxetine treatment. Psychopharmacology 233, 3259–3267 (2016). https://doi.org/10.1007/s00213-016-4364-0

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    • DOI: https://doi.org/10.1007/s00213-016-4364-0

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