SSRI-antipsychotic combination in psychotic depression

Sertraline pharmacokinetics in the presence of olanzapine, a brief report from the STOP-PD study

Simon J C Davies, Benoit H. Mulsant, Alastair J. Flint, Barnett S. Meyers, Anthony J. Rothschild, Ellen M. Whyte, Margaret M. Kirshner, Denise Sorisio, Bruce G. Pollock, Robert Bies

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective 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. Methods 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. Results 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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)252-255
Number of pages4
JournalHuman Psychopharmacology
Volume31
Issue number3
DOIs
StatePublished - May 1 2016

Fingerprint

olanzapine
Sertraline
Antipsychotic Agents
Pharmacokinetics
Population

Keywords

  • olanzapine
  • pharmacokinetics
  • sertraline

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Pharmacology (medical)

Cite this

SSRI-antipsychotic combination in psychotic depression : Sertraline pharmacokinetics in the presence of olanzapine, a brief report from the STOP-PD study. / Davies, Simon J C; Mulsant, Benoit H.; Flint, Alastair J.; Meyers, Barnett S.; Rothschild, Anthony J.; Whyte, Ellen M.; Kirshner, Margaret M.; Sorisio, Denise; Pollock, Bruce G.; Bies, Robert.

In: Human Psychopharmacology, Vol. 31, No. 3, 01.05.2016, p. 252-255.

Research output: Contribution to journalArticle

Davies, SJC, Mulsant, BH, Flint, AJ, Meyers, BS, Rothschild, AJ, Whyte, EM, Kirshner, MM, Sorisio, D, Pollock, BG & Bies, R 2016, 'SSRI-antipsychotic combination in psychotic depression: Sertraline pharmacokinetics in the presence of olanzapine, a brief report from the STOP-PD study', Human Psychopharmacology, vol. 31, no. 3, pp. 252-255. https://doi.org/10.1002/hup.2532
Davies, Simon J C ; Mulsant, Benoit H. ; Flint, Alastair J. ; Meyers, Barnett S. ; Rothschild, Anthony J. ; Whyte, Ellen M. ; Kirshner, Margaret M. ; Sorisio, Denise ; Pollock, Bruce G. ; Bies, Robert. / SSRI-antipsychotic combination in psychotic depression : Sertraline pharmacokinetics in the presence of olanzapine, a brief report from the STOP-PD study. In: Human Psychopharmacology. 2016 ; Vol. 31, No. 3. pp. 252-255.
@article{e9d3e9ff8c8d41b9801fed726c55dd5b,
title = "SSRI-antipsychotic combination in psychotic depression: Sertraline pharmacokinetics in the presence of olanzapine, a brief report from the STOP-PD study",
abstract = "Objective 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. Methods 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. Results 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. Conclusion 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.",
keywords = "olanzapine, pharmacokinetics, sertraline",
author = "Davies, {Simon J C} and Mulsant, {Benoit H.} and Flint, {Alastair J.} and Meyers, {Barnett S.} and Rothschild, {Anthony J.} and Whyte, {Ellen M.} and Kirshner, {Margaret M.} and Denise Sorisio and Pollock, {Bruce G.} and Robert Bies",
year = "2016",
month = "5",
day = "1",
doi = "10.1002/hup.2532",
language = "English (US)",
volume = "31",
pages = "252--255",
journal = "Human Psychopharmacology",
issn = "0885-6222",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

TY - JOUR

T1 - SSRI-antipsychotic combination in psychotic depression

T2 - Sertraline pharmacokinetics in the presence of olanzapine, a brief report from the STOP-PD study

AU - Davies, Simon J C

AU - Mulsant, Benoit H.

AU - Flint, Alastair J.

AU - Meyers, Barnett S.

AU - Rothschild, Anthony J.

AU - Whyte, Ellen M.

AU - Kirshner, Margaret M.

AU - Sorisio, Denise

AU - Pollock, Bruce G.

AU - Bies, Robert

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Objective 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. Methods 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. Results 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. Conclusion 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.

AB - Objective 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. Methods 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. Results 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. Conclusion 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.

KW - olanzapine

KW - pharmacokinetics

KW - sertraline

UR - http://www.scopus.com/inward/record.url?scp=84963655959&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84963655959&partnerID=8YFLogxK

U2 - 10.1002/hup.2532

DO - 10.1002/hup.2532

M3 - Article

VL - 31

SP - 252

EP - 255

JO - Human Psychopharmacology

JF - Human Psychopharmacology

SN - 0885-6222

IS - 3

ER -