Case report: Avoiding intolerance to antipsychotics through a personalized treatment approach based on pharmacogenetics
IntroductionThe standard approach to treatment in psychiatry is known as “treatment as usual” (TAU), in which the same types of treatment are administered to a group of patients. TAU often requires numerous dose adjustments and medication changes due to ineffectiveness and/or the occurrence of adver...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1363051/full |
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| author | Liam Korošec Hudnik Tanja Blagus Sara Redenšek Trampuž Vita Dolžan Jurij Bon Jurij Bon Milica Pjevac |
| author_facet | Liam Korošec Hudnik Tanja Blagus Sara Redenšek Trampuž Vita Dolžan Jurij Bon Jurij Bon Milica Pjevac |
| author_sort | Liam Korošec Hudnik |
| collection | DOAJ |
| description | IntroductionThe standard approach to treatment in psychiatry is known as “treatment as usual” (TAU), in which the same types of treatment are administered to a group of patients. TAU often requires numerous dose adjustments and medication changes due to ineffectiveness and/or the occurrence of adverse drug reactions (ADRs). This process is not only time-consuming but also costly. Antipsychotic medications are commonly used to treat various psychiatric disorders such as schizophrenia and mood disorders. Some of the inter-individual differences in efficacy and ADRs observed in psychopharmacotherapy can be explained by genetic variability in the pharmacokinetics and pharmacodynamics of antipsychotics. A better understanding of (in)efficacy and possible ADRs can be achieved by pharmacogenetic analysis of genes involved in the metabolism of antipsychotics. Most psychotropic drugs are metabolized by genetically variable CYP2D6, CYP1A2, CYP3A4, and CYP2C19 enzymes. To demonstrate the utility of pharmacogenetic testing for tailoring antipsychotic treatment, in this paper, we present the case of a patient in whom a pharmacogenetic approach remarkably altered an otherwise intolerant or ineffective conventional TAU with antipsychotics.MethodsIn this case report, we present a 60-year-old patient with psychotic symptoms who suffered from severe extrapyramidal symptoms and a malignant neuroleptic syndrome during treatment with risperidone, fluphenazine, aripiprazole, brexpiprazole, and olanzapine. Therefore, we performed a pharmacogenetic analysis by genotyping common functional variants in genes involved in the pharmacokinetic pathways of prescribed antipsychotics, namely, CYP2D6, CYP3A4, CYP3A5, CYP1A2, ABCB1, and ABCG2. Treatment recommendations for drug–gene pairs were made according to available evidence-based pharmacogenetic recommendations from the Dutch Pharmacogenetics Working Group (DPWG) or Clinical Pharmacogenetics Implementation Consortium (CPIC).ResultsPharmacogenetic testing revealed a specific metabolic profile and pharmacokinetic phenotype of the patient, which in retrospect provided possible explanations for the observed ADRs. Based on the pharmacogenetic results, the choice of an effective and safe medication proved to be much easier. The psychotic symptoms disappeared after treatment, while the negative symptoms persisted to a lesser extent.ConclusionWith the case presented, we have shown that taking into account the pharmacogenetic characteristics of the patient can explain the response to antipsychotic treatment and associated side effects. In addition, pharmacogenetic testing enabled an informed choice of the most appropriate drug and optimal dose adjustment. This approach makes it possible to avoid or minimize potentially serious dose-related ADRs and treatment ineffectiveness. However, due to the complexity of psychopathology and the polypharmacy used in this field, it is of great importance to conduct further pharmacokinetic and pharmacogenetic studies to better assess gene–drug and gene–gene–drug interactions. |
| first_indexed | 2024-04-24T22:40:48Z |
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| language | English |
| last_indexed | 2024-04-24T22:40:48Z |
| publishDate | 2024-03-01 |
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| series | Frontiers in Psychiatry |
| spelling | doaj.art-c43f758e11c2456d86aa50de181909412024-03-19T04:43:37ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402024-03-011510.3389/fpsyt.2024.13630511363051Case report: Avoiding intolerance to antipsychotics through a personalized treatment approach based on pharmacogeneticsLiam Korošec Hudnik0Tanja Blagus1Sara Redenšek Trampuž2Vita Dolžan3Jurij Bon4Jurij Bon5Milica Pjevac6Centre 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, 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, SloveniaIntroductionThe standard approach to treatment in psychiatry is known as “treatment as usual” (TAU), in which the same types of treatment are administered to a group of patients. TAU often requires numerous dose adjustments and medication changes due to ineffectiveness and/or the occurrence of adverse drug reactions (ADRs). This process is not only time-consuming but also costly. Antipsychotic medications are commonly used to treat various psychiatric disorders such as schizophrenia and mood disorders. Some of the inter-individual differences in efficacy and ADRs observed in psychopharmacotherapy can be explained by genetic variability in the pharmacokinetics and pharmacodynamics of antipsychotics. A better understanding of (in)efficacy and possible ADRs can be achieved by pharmacogenetic analysis of genes involved in the metabolism of antipsychotics. Most psychotropic drugs are metabolized by genetically variable CYP2D6, CYP1A2, CYP3A4, and CYP2C19 enzymes. To demonstrate the utility of pharmacogenetic testing for tailoring antipsychotic treatment, in this paper, we present the case of a patient in whom a pharmacogenetic approach remarkably altered an otherwise intolerant or ineffective conventional TAU with antipsychotics.MethodsIn this case report, we present a 60-year-old patient with psychotic symptoms who suffered from severe extrapyramidal symptoms and a malignant neuroleptic syndrome during treatment with risperidone, fluphenazine, aripiprazole, brexpiprazole, and olanzapine. Therefore, we performed a pharmacogenetic analysis by genotyping common functional variants in genes involved in the pharmacokinetic pathways of prescribed antipsychotics, namely, CYP2D6, CYP3A4, CYP3A5, CYP1A2, ABCB1, and ABCG2. Treatment recommendations for drug–gene pairs were made according to available evidence-based pharmacogenetic recommendations from the Dutch Pharmacogenetics Working Group (DPWG) or Clinical Pharmacogenetics Implementation Consortium (CPIC).ResultsPharmacogenetic testing revealed a specific metabolic profile and pharmacokinetic phenotype of the patient, which in retrospect provided possible explanations for the observed ADRs. Based on the pharmacogenetic results, the choice of an effective and safe medication proved to be much easier. The psychotic symptoms disappeared after treatment, while the negative symptoms persisted to a lesser extent.ConclusionWith the case presented, we have shown that taking into account the pharmacogenetic characteristics of the patient can explain the response to antipsychotic treatment and associated side effects. In addition, pharmacogenetic testing enabled an informed choice of the most appropriate drug and optimal dose adjustment. This approach makes it possible to avoid or minimize potentially serious dose-related ADRs and treatment ineffectiveness. However, due to the complexity of psychopathology and the polypharmacy used in this field, it is of great importance to conduct further pharmacokinetic and pharmacogenetic studies to better assess gene–drug and gene–gene–drug interactions.https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1363051/fullgene-drug interactionpsychopharmacologyextrapyramidal adverse effectspersonalized treatmentantipsychotics |
| spellingShingle | Liam Korošec Hudnik Tanja Blagus Sara Redenšek Trampuž Vita Dolžan Jurij Bon Jurij Bon Milica Pjevac Case report: Avoiding intolerance to antipsychotics through a personalized treatment approach based on pharmacogenetics Frontiers in Psychiatry gene-drug interaction psychopharmacology extrapyramidal adverse effects personalized treatment antipsychotics |
| title | Case report: Avoiding intolerance to antipsychotics through a personalized treatment approach based on pharmacogenetics |
| title_full | Case report: Avoiding intolerance to antipsychotics through a personalized treatment approach based on pharmacogenetics |
| title_fullStr | Case report: Avoiding intolerance to antipsychotics through a personalized treatment approach based on pharmacogenetics |
| title_full_unstemmed | Case report: Avoiding intolerance to antipsychotics through a personalized treatment approach based on pharmacogenetics |
| title_short | Case report: Avoiding intolerance to antipsychotics through a personalized treatment approach based on pharmacogenetics |
| title_sort | case report avoiding intolerance to antipsychotics through a personalized treatment approach based on pharmacogenetics |
| topic | gene-drug interaction psychopharmacology extrapyramidal adverse effects personalized treatment antipsychotics |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1363051/full |
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