Differentiated effects of the multimodal antidepressant vortioxetine on sleep architecture: Part 1, a pharmacokinetic/pharmacodynamic comparison with paroxetine in healthy men

J Psychopharmacol. 2015 Oct;29(10):1085-91. doi: 10.1177/0269881115599387. Epub 2015 Aug 7.


We compared the effect of vortioxetine, paroxetine and placebo after three days of dosing on sleep architecture. This was a randomised, double-blind, four-way crossover, placebo-controlled, multiple-dose study in 24 healthy young men. Subjects received 20mg vortioxetine, 40 mg vortioxetine, 20mg paroxetine or placebo for three consecutive days in four different periods with at least three weeks between them. Polysomnography and blood sampling for pharmacokinetic analysis were performed on the pre-dose night and nights 1 and 3 of dosing in each period. Plasma concentrations of vortioxetine and paroxetine during the polysomnography measurement were used to estimate SERT occupancies using published relationships in healthy subjects.All three active treatments significantly increased REM onset latency and decreased time spent in REM sleep. In the pharmacokinetic/pharmacodynamics analysis significant relationships were found between REM onset latency and time spent in REM sleep and vortioxetine/paroxetine exposure. The relation between REM suppression parameters and SERT occupancy was significantly different between vortioxetine and paroxetine, despite the same SERT occupancy. This indicates that vortioxetine has a different clinical pharmacological profile from paroxetine, which may explain the differences in adverse effect profile of the two drugs, for instance the lower incidence of nausea, weight gain and sexual dysfunction with vortioxetine.

Keywords: Sleep; serotonin; vortioxetine.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / blood
  • Antidepressive Agents, Second-Generation / pharmacokinetics*
  • Antidepressive Agents, Second-Generation / pharmacology*
  • Cross-Over Studies
  • Double-Blind Method
  • Healthy Volunteers
  • Humans
  • Male
  • Paroxetine / blood
  • Paroxetine / pharmacokinetics*
  • Paroxetine / pharmacology*
  • Piperazines / blood
  • Piperazines / pharmacokinetics*
  • Piperazines / pharmacology*
  • Polysomnography / methods
  • Selective Serotonin Reuptake Inhibitors / blood
  • Selective Serotonin Reuptake Inhibitors / pharmacokinetics
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Sleep, REM / drug effects*
  • Sulfides / blood
  • Sulfides / pharmacokinetics*
  • Sulfides / pharmacology*
  • Vortioxetine
  • Young Adult


  • Antidepressive Agents, Second-Generation
  • Piperazines
  • Serotonin Uptake Inhibitors
  • Sulfides
  • Vortioxetine
  • Paroxetine