Trial reportClinical pharmacokinetics2015
The Impact of Sertraline Co-Administration on the Pharmacokinetics of Olanzapine: A Population Pharmacokinetic Analysis of the STOP-PD.
Trial report in Clinical pharmacokinetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Population pharmacokinetics analysis of olanzapine for Chinese psychotic patients based on clinical therapeutic drug monitoring data with assistance of meta-analysis.European journal of clinical pharmacology · 2016Pooled it
- Effect of olanzapine exposure on relapse and brain structure in patients with major depressive disorder with psychotic features.Molecular psychiatry · 2024Trial
- Associations of CYP2B6, CYP2C19, and CYP2D6 isoforms and phenoconversion with sertraline pharmacokinetics.PloS one · 2026Article
- The Impact of Smoking, Sex, Infection, and Comedication Administration on Oral Olanzapine: A Population Pharmacokinetic Model in Chinese Psychiatric Patients.European journal of drug metabolism and pharmacokinetics · 2021Article
- Population pharmacokinetics of olanzapine in children.British journal of clinical pharmacology · 2021Article
- PharmGKB summary: sertraline pathway, pharmacokinetics.Pharmacogenetics and genomics · 2020Article
- Prediction of olanzapine exposure in individual patients using physiologically based pharmacokinetic modelling and simulation.British journal of clinical pharmacology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
objectiveClinical evidence and expert opinion support using a combination of an antipsychotic and an antidepressant when treating major depression with psychotic features. We characterized the impact of sertraline co-administration on olanzapine clearance in psychotic depression using population pharmacokinetic methods.
methodsThe Study of Pharmacotherapy for Psychotic Depression (STOP-PD) randomized 259 participants to olanzapine plus placebo or olanzapine plus sertraline. Olanzapine was started at 2.5-5 mg/day and sertraline at 25-50 mg/day. Doses were increased to a maximum of 20 mg/day for olanzapine and 200 mg/day for sertraline. Up to four olanzapine concentration samples were collected during the 12-week trial and 12-week continuation phase. We used NONMEM (Version VII) for population pharmacokinetic analysis, assessing effects of the covariates sex, African American origin, smoking, age, and sertraline co-administration.
resultsPopulation pharmacokinetic analysis comprised 336 samples from 175 individuals. The structural model published by Bigos et al. was sufficient to describe the olanzapine data adequately: a one-compartment model with first-order absorption and elimination, using an additive residual error structure with the absorption rate constant fixed to 0.5. Sertraline co-administration significantly increased olanzapine apparent clearance (p < 0.005) by 25-35 % depending on the patient characteristics included. Male sex was associated with a significantly increased clearance. Age and race did not have a significant impact on clearance.
conclusionsContrary to expectations from the knowledge of cytochrome P450 interactions, sertraline increased olanzapine apparent clearance. Plausible explanations include patients treated with sertraline having poorer adherence to olanzapine, or the impact of sertraline inhibition of transporters resulting in increased intracellular concentrations and thus access to metabolizing enzymes.
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Registered trials
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