title: SSRI-antipsychotic combination in psychotic depression: sertraline pharmacokinetics in the presence of olanzapine, a brief report from the STOP-PD study.
abstract: We recently reported an unexpected interaction between olanzapine and sertraline in a population being treated for psychotic depression. Contrary to knowledge of cytochrome p450 interactions sertraline increased apparent clearance of olanzapine by 30%. Here we examined the pharmacokinetics of sertraline in the same population. Existing studies suggest that sertraline apparent clearance is significantly increased in male subjects and suggested an age/sex interaction.
  
  
  
  We studied subjects undergoing combination of sertraline/olanzapine treatment for psychotic depression in the Study of the Pharmacotherapy of Psychotic Depression. Nonlinear mixed effect modelling software was used to examine the sertraline pharmacokinetics, evaluating age, sex, race, and olanzapine exposure as covariates.
  
  
  
  Eighty-seven subjects (median age 62 years, 28 male subjects, 11 African-Americans) provided 138 samples for sertraline concentration. Olanzapine exposure had a 14.8-fold range. A one compartment model with combined residual error described the sertraline concentration data adequately. Half-life and sex effect on sertraline apparent clearance (males averaging 50% higher (p < 0.005); 96.6 l/h vs 64.8 in female subjects) were similar to previous reports. No other covariate (age, race or olanzapine exposure) had a significant impact on apparent clearance, and no age/sex interaction emerged.
  
  
  
  Sertraline pharmacokinetics were similar to historical descriptions in populations not taking antipsychotics. Unlike our unexpected finding that sertraline increases olanzapine apparent clearance, olanzapine exposure had no impact on sertraline pharmacokinetics. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Centre for Addiction and Mental Health, Toronto, Canada.|Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: Simon J C
authors.initials: SJ
authors.lastname: Davies
authors.affiliation: Centre for Addiction and Mental Health, Toronto, Canada.|Department of Psychiatry, University of Toronto, Toronto, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada.|Department of Psychiatry, University Health Network, Toronto, Canada.
authors.forename: Alastair J
authors.initials: AJ
authors.lastname: Flint
authors.affiliation: Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY, USA.
authors.forename: Barnett S
authors.initials: BS
authors.lastname: Meyers
authors.affiliation: University of Massachusetts Medical School and University of Massachusetts Memorial Health Care, Worcester, MA, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Rothschild
authors.affiliation: Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Whyte
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Kirshner
authors.affiliation: Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Sorisio
authors.affiliation: Centre for Addiction and Mental Health, Toronto, Canada.|Department of Psychiatry, University of Toronto, Toronto, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.affiliation: Centre for Addiction and Mental Health, Toronto, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.|Indiana Clinical and Translational Sciences Institute (CTSI), Indianapolis, IN, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Bies
mesh_terms: D000328:Adult; D000367:Age Factors; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D017711:Nonlinear Dynamics; D000077152:Olanzapine; D011618:Psychotic Disorders / Q000188:drug therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D020280:Sertraline / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012737:Sex Factors
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
keywords: olanzapine; pharmacokinetics; sertraline