52.2 AN UPDATE ON GENE-MEDICATION INTERACTIONS RELEVANT TO PEDIATRIC PSYCHOPHARMACOTHERAPY

Abstract

Pharmacogenetic studies of pediatric patients are scarce, but clinicians frequently obtain pharmacogenetic testing in children and adolescents. This presentation will review the influence of pharmacokinetic and pharmacodynamic genes on response to antidepressants in youth. A review of the evidence for key pharmacokinetic and pharmacodynamic genes that impact medication tolerability and response in youth will be provided. Specifically, recent studies from our group reporting how: 1) CYP2C19 influences sertraline and escitalopram tolerability; 2) pharmacodynamic genes encoding the serotonin transporter and receptor 2A, SLC6A4, and HTR2A, influence SSRI response; and 3) MTHFR and L-methylfolate do not influence response to antidepressants. Two large retrospective studies in pediatric patients with anxiety and/or depressive disorders reported how CYP2C19 influences response and tolerability to escitalopram (N = 248) and sertraline (N = 352). Another study in a similar population (N = 164) indicated that the response to fluoxetine was associated with SLC6A4 and HTR2A variants but not CYP2D6. One prospective study of patients with anxiety disorders (N = 26) demonstrated that CYP2C19, SLC6A4, and HTR2A were associated with escitalopram response trajectory. In a retrospective analysis of patients that had MTHFR genotyping (n = 292), 23% received L-methylfolate supplementation. Neither the MTHFR genotypes nor L-methylfolate supplementation influenced response to antidepressants. Pharmacogenes are associated with both response and tolerability in youth treated with antidepressants in retrospective studies. Child and adolescent psychiatrists should know the evidence behind these studies as they consider use of pharmacogenetic testing in their clinical practice.