title: Differentiated effects of the multimodal antidepressant vortioxetine on sleep architecture: Part 1, a pharmacokinetic/pharmacodynamic comparison with paroxetine in healthy men.
abstract: 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.
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, UK sue.wilson@imperial.ac.uk.
authors.forename: Sue
authors.initials: S
authors.lastname: Wilson
authors.affiliation: Lundbeck A/S, Clinical and Quantitative Pharmacology, Copenhagen-Valby, Denmark.
authors.forename: Astrid-Maria
authors.initials: AM
authors.lastname: Højer
authors.affiliation: Lundbeck A/S, Clinical and Quantitative Pharmacology, Copenhagen-Valby, Denmark.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Buchberg
authors.affiliation: Lundbeck A/S, Clinical and Quantitative Pharmacology, Copenhagen-Valby, Denmark.
authors.forename: Johan
authors.initials: J
authors.lastname: Areberg
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D017374:Paroxetine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D017286:Polysomnography / Q000379:methods; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D012895:Sleep, REM / Q000187:drug effects*; D013440:Sulfides / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000078784:Vortioxetine; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D013440:Sulfides; D000078784:Vortioxetine
keywords: Sleep; serotonin; vortioxetine