Pharmacogenetics to Predict Adverse Events Associated With Antidepressants.
Adolescent
Antidepressive Agents
/ adverse effects
Child
Cytochrome P-450 CYP2C19
/ genetics
Depression
/ drug therapy
Drug-Related Side Effects and Adverse Reactions
/ genetics
Female
Follow-Up Studies
Genotype
Humans
Male
Pharmacogenetics
/ methods
Phenotype
Polymorphism, Genetic
Retrospective Studies
Selective Serotonin Reuptake Inhibitors
/ adverse effects
Journal
Pediatrics
ISSN: 1098-4275
Titre abrégé: Pediatrics
Pays: United States
ID NLM: 0376422
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
accepted:
02
09
2020
pubmed:
26
11
2020
medline:
20
1
2021
entrez:
25
11
2020
Statut:
ppublish
Résumé
To determine the association between cytochrome P450 2C19 (CYP2C19) metabolizer status and risk for escitalopram and citalopram, collectively termed (es)citalopram, and sertraline adverse events (AEs) in children. In this retrospective cohort study, we used deidentified electronic health records linked to DNA. The cohort included children ≤18 years with ≥2 days of (es)citalopram or ≥7 days of sertraline exposure. The primary outcome was AEs assessed by manual chart review. The cohort included 249 sertraline-exposed and 458 (es)citalopram-exposed children, with a median age of 14.2 years (interquartile range 11.2-16.2) and 13.4 years (interquartile range 10.1-15.9), respectively. Sertraline AEs were more common in normal metabolizers (NMs) compared to poor metabolizers (PMs) or intermediate metabolizers (IMs) (hazard ratio [HR] 1.8; 95% confidence interval [CI] 1.01-3.2; In contrast to adults, in our pediatric cohort, CYP2C19 NMs experienced increased sertraline AEs than PMs and IMs. (Es)citalopram AEs were not associated with CYP2C19 status in the primary analysis. The mechanism underlying this pediatric-specific finding is unknown but may be related to physiologic differences of adolescence. Further research is required to inform genotype-guided prescribing for these drugs in children.
Identifiants
pubmed: 33234666
pii: peds.2020-0957
doi: 10.1542/peds.2020-0957
pmc: PMC7786826
pii:
doi:
Substances chimiques
Antidepressive Agents
0
Serotonin Uptake Inhibitors
0
Cytochrome P-450 CYP2C19
EC 1.14.14.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM007569
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000445
Pays : United States
Informations de copyright
Copyright © 2020 by the American Academy of Pediatrics.
Déclaration de conflit d'intérêts
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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