English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

OBJECTIVES: 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. METHODS: 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. CYP2C19 was genotyped for functional variants (*2, *3, *4, *6, *8, and *17), and individuals were assigned metabolizer status. Association between AEs and metabolizer status was determined by using Cox regression adjusting for age, race, ethnicity, dose, and concomitant CYP2C19-inhibiting medications. RESULTS: 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; P = .047) in unadjusted analysis and after adjustment (HR 1.9; CI 1.04–3.4; P = .04). For (es)citalopram, more AEs were observed in NMs than PMs and IMs without statistically significant differences (unadjusted HR 1.6; CI 0.95-2.6; P = .08; adjusted HR 1.6; CI 0.95-2.6; P = .08). CONCLUSIONS: 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.

Pharmacogenetics to Predict Adverse Events Associated With Antidepressants