Interest of Fluvoxamine as an Add-On to Clozapine in Children With Severe Psychiatric Disorder According to CYP Polymorphisms: Experience From a Case Series
Despite its drastic efficacy in resistant psychiatric disorders, clozapine remains rarely used in youth due to its side effects. Clozapine plasma level is determined through its metabolism involving several isoforms of cytochromes 450 (CYP450) family. Isoform CYP1A2 appears as a limiting enzyme invo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Psychiatry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2021.669446/full |
| _version_ | 1818926652642557952 |
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| author | Camille Berel Ulysse Mossé Julien Wils Julien Wils Lauriane Cousin Laurent Imbert Priscille Gerardin Priscille Gerardin Boris Chaumette Boris Chaumette Boris Chaumette Fabien Lamoureux Fabien Lamoureux Vladimir Ferrafiat Vladimir Ferrafiat |
| author_facet | Camille Berel Ulysse Mossé Julien Wils Julien Wils Lauriane Cousin Laurent Imbert Priscille Gerardin Priscille Gerardin Boris Chaumette Boris Chaumette Boris Chaumette Fabien Lamoureux Fabien Lamoureux Vladimir Ferrafiat Vladimir Ferrafiat |
| author_sort | Camille Berel |
| collection | DOAJ |
| description | Despite its drastic efficacy in resistant psychiatric disorders, clozapine remains rarely used in youth due to its side effects. Clozapine plasma level is determined through its metabolism involving several isoforms of cytochromes 450 (CYP450) family. Isoform CYP1A2 appears as a limiting enzyme involved in the metabolism of clozapine, while isoforms 2C19, 2D6, 3A4, and 3A5 also contribute in a minor way. Clozapine efficacy is limited by a significant inter-patient variability in exposure according to CYP's polymorphisms. Clozapine plasma levels may be increased with CYP inhibitors such as fluvoxamine. This drug is a potent enzymatic inhibitor of CYP1A2 and, to a lesser extent, of CYP3A4 and CYP2D6. Hence, in case of CYP's polymorphisms in youth, the use of fluvoxamine as add-on to clozapine could help in reaching clinical and biological efficacy and allowing lower clozapine dosage and a better tolerance profile as it has already been described in adults. We report four pediatric cases with severe psychiatric disorders underlying our experience with CYP polymorphism explorations and the use of fluvoxamine as add-on to clozapine. Our four patients clinically improved after the introduction of fluvoxamine, enhancing clozapine metabolism and therefore the clozapine plasma level within therapeutic range. Despite the interesting results of fluvoxamine, we report a severe issue of tolerance for one patient, emphasizing the need for caution regarding possible drug interactions when fluvoxamine is considered. Hence, we propose a detailed step-by-step multidisciplinary protocol. |
| first_indexed | 2024-12-20T03:00:32Z |
| format | Article |
| id | doaj.art-3ef8c8046a9c4b18a7f9e924fe927b97 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-20T03:00:32Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-3ef8c8046a9c4b18a7f9e924fe927b972022-12-21T19:55:47ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402021-06-011210.3389/fpsyt.2021.669446669446Interest of Fluvoxamine as an Add-On to Clozapine in Children With Severe Psychiatric Disorder According to CYP Polymorphisms: Experience From a Case SeriesCamille Berel0Ulysse Mossé1Julien Wils2Julien Wils3Lauriane Cousin4Laurent Imbert5Priscille Gerardin6Priscille Gerardin7Boris Chaumette8Boris Chaumette9Boris Chaumette10Fabien Lamoureux11Fabien Lamoureux12Vladimir Ferrafiat13Vladimir Ferrafiat14Child and Adolescent Psychiatric Unit, URHEA, CHSR Sotteville les Rouen, Sotteville les Rouen, FranceChild and Adolescent Psychiatric Unit, URHEA, CHSR Sotteville les Rouen, Sotteville les Rouen, FranceDepartment of Pharmacology – Toxicology and Pharmacogenetics, Rouen University Hospital, Rouen, FranceNormandie Univ, UNIROUEN, Inserm U1096, Rouen, FranceChild and Adolescent Psychiatric Department, CHRU Lille, Lille, FranceDepartment of Pharmacology – Toxicology and Pharmacogenetics, Rouen University Hospital, Rouen, FranceChild and Adolescent Psychiatric Unit, URHEA, CHSR Sotteville les Rouen, Sotteville les Rouen, FranceChild and Adolescent Psychiatric Department, CHU Charles Nicolle, Rouen, FranceInstitut de Psychiatrie et Neurosciences de Paris, INSERM UMR 1266, Université de Paris, GDR3557-Institut de Psychiatrie, Paris, FranceGHU Paris Psychiatrie et Neurosciences, Paris, FranceDepartment of Psychiatry, McGill University, Montreal, QC, CanadaDepartment of Pharmacology – Toxicology and Pharmacogenetics, Rouen University Hospital, Rouen, FranceNormandie Univ, UNIROUEN, Inserm U1096, Rouen, FranceChild and Adolescent Psychiatric Unit, URHEA, CHSR Sotteville les Rouen, Sotteville les Rouen, FranceChild and Adolescent Psychiatric Department, CHU Charles Nicolle, Rouen, FranceDespite its drastic efficacy in resistant psychiatric disorders, clozapine remains rarely used in youth due to its side effects. Clozapine plasma level is determined through its metabolism involving several isoforms of cytochromes 450 (CYP450) family. Isoform CYP1A2 appears as a limiting enzyme involved in the metabolism of clozapine, while isoforms 2C19, 2D6, 3A4, and 3A5 also contribute in a minor way. Clozapine efficacy is limited by a significant inter-patient variability in exposure according to CYP's polymorphisms. Clozapine plasma levels may be increased with CYP inhibitors such as fluvoxamine. This drug is a potent enzymatic inhibitor of CYP1A2 and, to a lesser extent, of CYP3A4 and CYP2D6. Hence, in case of CYP's polymorphisms in youth, the use of fluvoxamine as add-on to clozapine could help in reaching clinical and biological efficacy and allowing lower clozapine dosage and a better tolerance profile as it has already been described in adults. We report four pediatric cases with severe psychiatric disorders underlying our experience with CYP polymorphism explorations and the use of fluvoxamine as add-on to clozapine. Our four patients clinically improved after the introduction of fluvoxamine, enhancing clozapine metabolism and therefore the clozapine plasma level within therapeutic range. Despite the interesting results of fluvoxamine, we report a severe issue of tolerance for one patient, emphasizing the need for caution regarding possible drug interactions when fluvoxamine is considered. Hence, we propose a detailed step-by-step multidisciplinary protocol.https://www.frontiersin.org/articles/10.3389/fpsyt.2021.669446/fullclozapineresistant psychiatric disorderchild and adolescent psychiatrycytochrome polymorphismfluvoxamine |
| spellingShingle | Camille Berel Ulysse Mossé Julien Wils Julien Wils Lauriane Cousin Laurent Imbert Priscille Gerardin Priscille Gerardin Boris Chaumette Boris Chaumette Boris Chaumette Fabien Lamoureux Fabien Lamoureux Vladimir Ferrafiat Vladimir Ferrafiat Interest of Fluvoxamine as an Add-On to Clozapine in Children With Severe Psychiatric Disorder According to CYP Polymorphisms: Experience From a Case Series Frontiers in Psychiatry clozapine resistant psychiatric disorder child and adolescent psychiatry cytochrome polymorphism fluvoxamine |
| title | Interest of Fluvoxamine as an Add-On to Clozapine in Children With Severe Psychiatric Disorder According to CYP Polymorphisms: Experience From a Case Series |
| title_full | Interest of Fluvoxamine as an Add-On to Clozapine in Children With Severe Psychiatric Disorder According to CYP Polymorphisms: Experience From a Case Series |
| title_fullStr | Interest of Fluvoxamine as an Add-On to Clozapine in Children With Severe Psychiatric Disorder According to CYP Polymorphisms: Experience From a Case Series |
| title_full_unstemmed | Interest of Fluvoxamine as an Add-On to Clozapine in Children With Severe Psychiatric Disorder According to CYP Polymorphisms: Experience From a Case Series |
| title_short | Interest of Fluvoxamine as an Add-On to Clozapine in Children With Severe Psychiatric Disorder According to CYP Polymorphisms: Experience From a Case Series |
| title_sort | interest of fluvoxamine as an add on to clozapine in children with severe psychiatric disorder according to cyp polymorphisms experience from a case series |
| topic | clozapine resistant psychiatric disorder child and adolescent psychiatry cytochrome polymorphism fluvoxamine |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2021.669446/full |
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