Interest of Fluvoxamine as an Add-On to Clozapine in Children With Severe Psychiatric Disorder According to CYP Polymorphisms: Experience From a Case Series.
child and adolescent psychiatry
clozapine
cytochrome polymorphism
fluvoxamine
resistant psychiatric disorder
Journal
Frontiers in psychiatry
ISSN: 1664-0640
Titre abrégé: Front Psychiatry
Pays: Switzerland
ID NLM: 101545006
Informations de publication
Date de publication:
2021
2021
Historique:
received:
18
02
2021
accepted:
21
05
2021
entrez:
8
7
2021
pubmed:
9
7
2021
medline:
9
7
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34234701
doi: 10.3389/fpsyt.2021.669446
pmc: PMC8255476
doi:
Types de publication
Journal Article
Langues
eng
Pagination
669446Informations de copyright
Copyright © 2021 Berel, Mossé, Wils, Cousin, Imbert, Gerardin, Chaumette, Lamoureux and Ferrafiat.
Déclaration de conflit d'intérêts
BC has received speaking fees from Janssen-Cilag. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Psychopharmacology (Berl). 2014 Mar;231(6):1023-36
pubmed: 23552907
J Clin Psychiatry. 2007 May;68(5):697-704
pubmed: 17503978
Psychiatr Clin North Am. 2016 Jun;39(2):239-65
pubmed: 27216902
Am J Psychiatry. 1996 May;153(5):738
pubmed: 8615435
J Child Adolesc Psychopharmacol. 2013 Oct;23(8):516-21
pubmed: 24111981
Pharmacogenet Genomics. 2018 Sep;28(9):214-222
pubmed: 30134346
J Clin Psychiatry. 2001 Jun;62(6):479-80
pubmed: 11465533
J Child Adolesc Psychopharmacol. 2010 Feb;20(1):79-80
pubmed: 20166802
Neuropsychiatr Dis Treat. 2015 Apr 01;11:907-13
pubmed: 25897226
Expert Opin Drug Metab Toxicol. 2012 Mar;8(3):371-82
pubmed: 22288606
Pharmgenomics Pers Med. 2017 Aug 28;10:235-242
pubmed: 28919802
Early Interv Psychiatry. 2013 May;7(2):122-30
pubmed: 22747759
Asian J Psychiatr. 2017 Oct;29:194-195
pubmed: 28704788
Curr Drug Targets. 2018;19(1):38-54
pubmed: 28124606
Autism. 2015 Jan;19(1):102-6
pubmed: 24571823
Child Adolesc Psychiatr Clin N Am. 2013 Oct;22(4):727-44
pubmed: 24012083
Child Adolesc Psychiatr Clin N Am. 2020 Jan;29(1):71-90
pubmed: 31708054
J Am Acad Child Adolesc Psychiatry. 2005 Mar;44(3):213-35
pubmed: 15725966
Food Sci Nutr. 2014 Sep;2(5):500-20
pubmed: 25473508
Biol Psychiatry. 1995 Aug 1;38(3):196-7
pubmed: 7578666
Paediatr Drugs. 2005;7(5):277-94
pubmed: 16220995
Pharmacol Ther. 2013 Apr;138(1):103-41
pubmed: 23333322
Clin Psychopharmacol Neurosci. 2019 Feb 28;17(1):43-53
pubmed: 30690939
CNS Neurol Disord Drug Targets. 2009 Dec;8(6):470-4
pubmed: 19702566
Clin Neuropharmacol. 2009 May-Jun;32(3):154-7
pubmed: 19483482
Toxicol Lett. 2016 Sep 6;258:55-70
pubmed: 27320963
Eur Psychiatry. 2014 Jan;29(1):1-10
pubmed: 24119631
Pharmacol Ther. 2007 Aug;115(2):223-31
pubmed: 17583355
J Child Adolesc Psychopharmacol. 2008 Aug;18(4):307-16
pubmed: 18759640
Biol Psychiatry. 1998 Oct 15;44(8):733-8
pubmed: 9798077
J Am Acad Child Adolesc Psychiatry. 2005 Jan;44(1):55-63
pubmed: 15608544
J Child Adolesc Psychopharmacol. 2016 Nov;26(9):843-846
pubmed: 26986554
J Am Acad Child Adolesc Psychiatry. 2007 Oct;46(10):1349-1356
pubmed: 17885577
J Child Adolesc Psychopharmacol. 2016 Nov;26(9):815-821
pubmed: 26771824
Can J Psychiatry. 2001 Dec;46(10):965-8
pubmed: 11816319
Med Hypotheses. 2013 Jun;80(6):689-91
pubmed: 23490199
Clin Pharmacol Ther. 2012 Oct;92(4):414-7
pubmed: 22992668
J Clin Psychopharmacol. 2004 Apr;24(2):214-9
pubmed: 15206669
Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):895-901
pubmed: 18398030
Pharmacopsychiatry. 2018 Jan;51(1-02):9-62
pubmed: 28910830
Schizophr Res. 2018 Mar;193:126-133
pubmed: 28688742
CNS Drugs. 2017 Mar;31(3):177-180
pubmed: 28258419
Neurosciences (Riyadh). 2003 Jul;8(3):198-200
pubmed: 23649120
J Can Acad Child Adolesc Psychiatry. 2021 Feb;30(1):36-48
pubmed: 33552171
Am J Psychiatry. 2007 Apr;164(4):663-9
pubmed: 17403981
Clin Pharmacol Ther. 2020 Aug;108(2):212-227
pubmed: 32086800
Arch Gen Psychiatry. 2006 Jun;63(6):622-9
pubmed: 16754835
J Am Acad Child Adolesc Psychiatry. 2013 Sep;52(9):976-90
pubmed: 23972700
J Neural Transm (Vienna). 2008 Nov;115(11):1599-608
pubmed: 18779922
J Clin Psychiatry. 2000 Aug;61(8):594-9
pubmed: 10982203
J Clin Psychopharmacol. 2011 Jun;31(3):341-4
pubmed: 21508854
ACS Chem Neurosci. 2014 Jan 15;5(1):24-9
pubmed: 24219174
Int Rev Neurobiol. 2013;112:281-349
pubmed: 24295625
Neuropsychiatr Dis Treat. 2016 Jun 23;12:1525-38
pubmed: 27382295
Biomed Res Int. 2020 Jan 7;2020:9872936
pubmed: 31998804
Eur Neuropsychopharmacol. 2015 Jun;25(6):857-63
pubmed: 25769917
J Child Adolesc Psychopharmacol. 2015 Mar;25(2):188-90
pubmed: 25782101
J Clin Psychopharmacol. 2004 Feb;24(1):70-8
pubmed: 14709950
ACS Chem Neurosci. 2013 Jul 17;4(7):1018-25
pubmed: 24047509
Am J Psychiatry. 1979 Mar;136(3):317-20
pubmed: 154301
Drug Metab Dispos. 2008 Dec;36(12):2547-55
pubmed: 18809730
Ann Genet. 2002 Apr-Jun;45(2):89-95
pubmed: 12119217
Arch Gen Psychiatry. 1996 Dec;53(12):1090-7
pubmed: 8956674
Paediatr Drugs. 2011 Oct 1;13(5):291-302
pubmed: 21888443
J Child Adolesc Psychopharmacol. 2013 Feb;23(1):44-8
pubmed: 23347126