SHORT COMMUNICATION 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 1,2 *, Benoit H. Mulsant 1,2,3 , Alastair J. Flint 2,4 , Barnett S. Meyers 5 , Anthony J. Rothschild 6 , Ellen M. Whyte 7 , Margaret M. Kirshner 8 , Denise Sorisio 7 , Bruce G. Pollock 1,2,3 , Robert R. Bies 1,3,9 and for the STOP-PD study group 1 Centre for Addiction and Mental Health, Toronto, Canada 2 Department of Psychiatry, University of Toronto, Toronto, Canada 3 Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada 4 Department of Psychiatry, University Health Network, Toronto, Canada 5 Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY USA 6 University of Massachusetts Medical School and University of Massachusetts Memorial Health Care, Worcester, MA USA 7 Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA USA 8 Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA USA 9 Indiana Clinical and Translational Sciences Institute (CTSI), Indianapolis, IN USA Objective We recently reported an unexpected interaction between olanzapine and sertraline in a population being treated for psychotic depres- sion. 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 concentra- tion. 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); 96.6l/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. Copyright © 2016 John Wiley & Sons, Ltd. key words—sertraline; olanzapine; pharmacokinetics INTRODUCTION The selective serotonin reuptake inhibitor (SSRI) antide- pressant sertraline is considered a first line treatment of depression (Mulsant et al., 2014; Cleare et al., 2015) and several anxiety disorders (Baldwin et al., 2014). In meta-analysis, sertraline ranked highly among 12 antide- pressants for both efficacy in depression and tolerability (Cipriani et al., 2009). In major depression with psychotic features (‘psychotic depression’) clinical evidence and guidelines recommend use of an antidepressant and anti- psychotic in combination (Wijkstra et al., 2015). The Study of the Pharmacotherapy of Psychotic Depression (STOP-PD) (Meyers et al., 2009) is the largest placebo- controlled randomized trial for treatment of psychotic *Correspondence to: S. J. C. Davies, Centre for Addiction and Men- tal Health, 1001 Queen Street West, Toronto, ON, M6J 1H4, Canada. E-mail: simon_davies@camh.net Presentations: These data were presented as a poster at the British Associa- tion for Psychopharmacology Summer Meeting, Bristol, July 2015. Received 13 August 2015 Revised 11 February 2016 Accepted 24 February 2016 Copyright © 2016 John Wiley & Sons, Ltd. human psychopharmacology Hum. Psychopharmacol Clin Exp 2016; 31: 252–255 Published online 6 April 2016 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/hup.2532