Case Report: I want more olanzapine: pharmacogenetic insights into a patient's preference for high-dose olanzapine
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 report...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1633198/full |
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| author | Liam Korošec Hudnik Ivo Kosmačin Tanja Blagus Vita Dolžan Jurij Bon Jurij Bon Milica Pjevac Milica Pjevac |
| author_facet | Liam Korošec Hudnik Ivo Kosmačin Tanja Blagus Vita Dolžan Jurij Bon Jurij Bon Milica Pjevac Milica Pjevac |
| author_sort | Liam Korošec Hudnik |
| collection | DOAJ |
| description | 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.MethodsThe 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.ResultsGenotyping 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 non-smoker—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.ConclusionThis 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. |
| format | Article |
| id | doaj-art-5842771bfdac4d1d8822d03df4cb059a |
| institution | Kabale University |
| issn | 1664-0640 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj-art-5842771bfdac4d1d8822d03df4cb059a2025-08-20T03:50:06ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-07-011610.3389/fpsyt.2025.16331981633198Case Report: I want more olanzapine: pharmacogenetic insights into a patient's preference for high-dose olanzapineLiam Korošec Hudnik0Ivo Kosmačin1Tanja Blagus2Vita Dolžan3Jurij Bon4Jurij Bon5Milica Pjevac6Milica Pjevac7Centre for Clinical Psychiatry, University Psychiatric Clinic Ljubljana, Ljubljana, SloveniaCentre for Clinical Psychiatry, University Psychiatric Clinic Ljubljana, Ljubljana, SloveniaPharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaPharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaCentre for Clinical Psychiatry, University Psychiatric Clinic Ljubljana, Ljubljana, SloveniaDepartment of Psychiatry, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaCentre for Clinical Psychiatry, University Psychiatric Clinic Ljubljana, Ljubljana, SloveniaDepartment of Psychiatry, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaOlanzapine 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.MethodsThe 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.ResultsGenotyping 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 non-smoker—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.ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1633198/fullcase reportCYP1A2CYP2D6genetic polymorphismolanzapinepersonalized psychopharmacotherapy |
| spellingShingle | Liam Korošec Hudnik Ivo Kosmačin Tanja Blagus Vita Dolžan Jurij Bon Jurij Bon Milica Pjevac Milica Pjevac Case Report: I want more olanzapine: pharmacogenetic insights into a patient's preference for high-dose olanzapine Frontiers in Psychiatry case report CYP1A2 CYP2D6 genetic polymorphism olanzapine personalized psychopharmacotherapy |
| title | Case Report: I want more olanzapine: pharmacogenetic insights into a patient's preference for high-dose olanzapine |
| title_full | Case Report: I want more olanzapine: pharmacogenetic insights into a patient's preference for high-dose olanzapine |
| title_fullStr | Case Report: I want more olanzapine: pharmacogenetic insights into a patient's preference for high-dose olanzapine |
| title_full_unstemmed | Case Report: I want more olanzapine: pharmacogenetic insights into a patient's preference for high-dose olanzapine |
| title_short | Case Report: I want more olanzapine: pharmacogenetic insights into a patient's preference for high-dose olanzapine |
| title_sort | case report i want more olanzapine pharmacogenetic insights into a patient s preference for high dose olanzapine |
| topic | case report CYP1A2 CYP2D6 genetic polymorphism olanzapine personalized psychopharmacotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1633198/full |
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