SSRI-antipsychotic combination in psychotic depression: sertraline pharmacokinetics in the presence of olanzapine, a brief report from the STOP-PD study

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...

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Bibliographic Details
Published in:Human psychopharmacology 2016-05, Vol.31 (3), p.252-255
Main Authors: 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 R.
Format: Article
Language:English
Subjects:
Adult
Age Factors
Antipsychotic Agents - administration & dosage
Antipsychotic Agents - therapeutic use
Benzodiazepines - administration & dosage
Benzodiazepines - therapeutic use
Depressive Disorder, Major - drug therapy
Drug Interactions
Drug Therapy, Combination
Female
Half-Life
Humans
Male
Middle Aged
Models, Biological
Nonlinear Dynamics
Olanzapine
pharmacokinetics
Psychotic Disorders - drug therapy
Serotonin Uptake Inhibitors - administration & dosage
Serotonin Uptake Inhibitors - pharmacokinetics
Serotonin Uptake Inhibitors - therapeutic use
sertraline
Sertraline - administration & dosage
Sertraline - pharmacokinetics
Sertraline - therapeutic use
Sex Factors
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Summary: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 
ISSN:0885-6222
1099-1077
DOI:10.1002/hup.2532