# Improving the Effectiveness and Safety of Escitalopram in Pediatric Anxiety Disorders Using Pharmacogenetically-guided Dosing

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $680,585

## Abstract

PROJECT SUMMARY
Anxiety disorders are among the most prevalent psychiatric conditions in adolescents and are associated with
functional impairment and symptomatic distress. When untreated, they result in persistent disability into
adulthood. Moreover, nearly 40% of pediatric patients with anxiety disorders fail to respond to the first-line
psychopharmacologic treatment—selective serotonin reuptake inhibitors (SSRIs)—and up to 70% will
experience treatment-limiting side effects. Identifying predictors of treatment response in pediatric patients
provides an opportunity to (1) optimize treatment, (2) forestall the development of secondary psychopathology
and suicide attempts and (3) restore normal psychosocial function and quality of life. In this regard, in adults,
pharmacogenetically (PGx)-guided antidepressant treatment increases efficacy, decreases side effect burden
and reduces treatment costs; however, these PGx studies involving adults focus almost exclusively on
medication selection rather than dosing. Currently, there are no such pediatric trials. Despite the availability of
PGx dosing guidelines for adults, blinded, randomized trials of PGx-guided SSRI dosing have never been
conducted (even in adults). Compared to adults, SSRI-related side effects and pharmacokinetics significantly
differ in adolescents. This proposal aims to test whether PGx-guided dosing of the SSRI, escitalopram,
improves efficacy and tolerability in adolescents with anxiety disorders. We will measure treatment response
with the Pediatric Anxiety Rating Scale (PARS, a validated measure of pediatric anxiety symptom severity)
after 12 weeks of escitalopram treatment. Additionally, activation and weight gain—two significant side effects
of SSRIs in youth—will be assessed with the Treatment Emergent Activation and Suicidality Assessment
Profile and body mass index (BMI) during the 12 week trial. Adolescents with anxiety disorders (N=132) will be
randomized (1:1) to receive (1) standard or (2) PGx-guided escitalopram dosing. We expect greater reduction
in PARS scores over time (i.e., better response) with PGx-guided dosing compared to standard dosing.
Further, we expect more patients to experience activation and treatment-related BMI increases with standard
dosing compared to PGx-guided dosing. Additionally, we will examine the influence of CYP2C19 metabolizer
status on escitalopram pharmacokinetics and will determine the impact of serotonin transporter (SLC6A4) and
receptor (HTR2A) variants on treatment response. For treatment of pediatric anxiety to move beyond the
current "one-size fits all" approach, PGx-guided SSRI dosing strategies are urgently needed. This study will
provide clinicians, patients, parents, and payers the evidence to determine whether PGx-guided escitalopram
dosing in pediatric anxiety disorders has clinical utility.

## Key facts

- **NIH application ID:** 9991480
- **Project number:** 1R01HD099775-01A1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Laura B Ramsey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $680,585
- **Award type:** 1
- **Project period:** 2020-09-21 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991480

## Citation

> US National Institutes of Health, RePORTER application 9991480, Improving the Effectiveness and Safety of Escitalopram in Pediatric Anxiety Disorders Using Pharmacogenetically-guided Dosing (1R01HD099775-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9991480. Licensed CC0.

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