title: Lack of Effect of Vortioxetine on the Pharmacokinetics and Pharmacodynamics of Ethanol, Diazepam, and Lithium.
abstract: Because the multimodal antidepressant vortioxetine is likely to be coadministered with other central nervous system (CNS)-active drugs, potential drug-drug interactions warrant examination.
  
  
  
  These studies evaluated whether there are pharmacokinetic and/or pharmacodynamic interactions between vortioxetine and ethanol, diazepam, or lithium.
  
  
  
  This series of phase I studies included healthy men and women (only men in the lithium study) aged 18-45 years. The ethanol study was a randomized, double-blind, two-parallel group, four-period crossover study in which subjects received a single dose of vortioxetine (20 or 40 mg) or placebo with or without ethanol, and the diazepam study was a randomized, double-blind, placebo-controlled, two-sequence, two-period crossover study in which subjects received a single dose of diazepam following multiple doses of vortioxetine 10 mg/day or placebo. These two studies evaluated the effect of coadministration on standardized psychomotor parameters and on selected pharmacokinetic parameters of each drug. The lithium study was a single-blind, single-sequence study evaluating the effect of multiple doses of vortioxetine 10 mg/day on the steady-state pharmacokinetics of lithium.
  
  
  
  Concomitant administration of vortioxetine and single doses of either ethanol or diazepam had no significant effect on the psychomotor performance of subjects compared with administration of ethanol or diazepam alone. Vortioxetine had no significant effect on the pharmacokinetics of ethanol, diazepam, or lithium, and ethanol had no significant effect on the pharmacokinetics of vortioxetine.
  
  
  
  Concomitant administration of these agents with vortioxetine was generally well tolerated, with no clinically relevant drug-drug pharmacokinetic or pharmacodynamic interactions identified.
authors.affiliation: Clinical Pharmacology, Takeda Development Center Americas, Inc., One Takeda Parkway, Deerfield, IL, 60015, USA. grace.chen@takeda.com.
authors.forename: Grace
authors.initials: G
authors.lastname: Chen
authors.affiliation: Clinical Science, Takeda Development Center Americas, Inc., One Takeda Parkway, Deerfield, IL, 60015, USA.
authors.forename: George G
authors.initials: GG
authors.lastname: Nomikos
authors.affiliation: Pharmacovigilance, Takeda Development Center Americas, Inc., One Takeda Parkway, Deerfield, IL, 60015, USA.
authors.forename: John
authors.initials: J
authors.lastname: Affinito
authors.affiliation: Analytical Science, Takeda Development Center Americas, Inc., One Takeda Parkway, Deerfield, IL, 60015, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003975:Diazepam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008094:Lithium / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D013440:Sulfides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000078784:Vortioxetine; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D013440:Sulfides; D000431:Ethanol; D000078784:Vortioxetine; D008094:Lithium; D003975:Diazepam