Selective serotonin reuptake inhibitors (SSRIs) are widely employed in treating pediatric anxiety disorders like generalized anxiety disorder (GAD). But forecasting their efficacy and tolerability are challenging. 

The efficacy and tolerability of escitalopram in adolescents with GAD (DSM-IV-TR) and the impact of variants in HTR2A and serotonin transporter (SLC6A4) genes and cytochrome P450 2C19 (CYP2C19) phenotypes on response as well as CYP2C19 phenotype on escitalopram pharmacokinetics were evaluated in a study.

The enrolled individuals were given escitalopram (forced titration to 15 mg/d, followed by flexible titration to 20 mg/d) or a placebo for 8 weeks. The change in scores on the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Impressions (CGI) scales and vital signs and adverse events were noted. Plasma escitalopram and desmethylcitalopram area under the curve for 24 hours (AUC0-24) and maximum concentration (Cmax) were evaluated and compared across CYP2C19 phenotypes.

Escitalopram overrode placebo regarding the baseline-to-endpoint change in PARS and CGI scores, and expanding CYP2C19 metabolism was linked with declines in escitalopram Cmax and AUC0-24. 

Vital signs, corrected QT interval, and adverse events were similar in escitalopram and placebo groups.

Thus, Escitalopram ameliorates anxiety symptoms, and pharmacogenetic variables influence the trajectory and magnitude of improvement. The difference in CYP2C19 metabolism causes substantial differences in escitalopram pharmacokinetics, suggesting considering CYP2C19 phenotype while prescribing escitalopram.

Jeffrey R. Strawn, MD; Jeffrey A. Mills, PhD; Heidi Schroeder, BS; Sarah A. Mossman, MACPR; Sara T. Varney, BS; Laura B. Ramsey, PhD; Ethan A. Poweleit, BS; Zeruesenay Desta, PhD; Kim Cecil, PhD; and Melissa P. DelBello. The journal of clinical psychiatry.https://www.psychiatrist.com/jcp/depression/escitalopram-in-adolescents-with-gad/#top