CASE REPORT article
Front. Psychiatry
Sec. Psychopharmacology
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1633198
This article is part of the Research TopicCase Reports in Psychopharmacology, volume IIIView all 7 articles
A case report -»I want more olanzapine.«: Pharmacogenetic Insights Into a Patient's Preference for High-Dose Olanzapine
Provisionally accepted
- 1University Psychiatric Clinic, Ljubljana, Slovenia
- 2Univerza v Ljubljani Medicinska fakulteta, Ljubljana, Slovenia
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Olanzapine is an effective antipsychotic agent, but its metabolism shows considerable interindividual variability.We present a case of a patient with treatment-resistant schizophrenia who consistently required and preferred high-dose olanzapine (40-60 mg/day) for symptom control. The patient reported improved motivation and energy following the reduction of adjunctive antipsychotics.Methods: The patient's clinical course and treatment history were retrospectively reviewed. Plasma olanzapine levels were measured to assess systemic drug exposure, and pharmacogenetic testing for CYP1A2, CYP2D6, CYP3A4, and CYP3A5 polymorphisms was performed using PCR-based genotyping.Results: Genotyping revealed CYP1A2 -163AA genotype, consistent with an ultrarapid metabolizer phenotype, and CYP2D6 *1/*9 genotype, indicating slightly reduced but overall normal enzyme activity. At 40 mg/day, the olanzapine trough level was 51 ng/mL-lower than expected for a nonsmoker-suggesting enhanced metabolic clearance. This pharmacokinetic profile, shaped by genetic predisposition and smoking, likely necessitated higher olanzapine doses to reach therapeutic levels. Discontinuation of haloperidol and risperidone was associated with improved subjective energy and engagement. Conclusion: This case illustrates how pharmacogenetic variability may influence antipsychotic efficacy and tolerability. The patient's ultrarapid CYP1A2 metabolism and smoking status likely reduced olanzapine exposure, warranting higher doses for clinical response. Pharmacogenetic profiling may provide valuable insights into individual treatment needs and support more personalized approaches in complex psychiatric cases.
Keywords: case report, CYP1A2, CYP2D6, Genetic polymorphism, olanzapine, Personalized psychopharmacotherapy, Pharmacogenetics, treatment resistance
Received: 22 May 2025; Accepted: 23 Jun 2025.
Copyright: © 2025 Korošec Hudnik, Kosmačin, Blagus, Dolzan, Bon and Pjevac. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Milica Pjevac, University Psychiatric Clinic, Ljubljana, Slovenia
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.