Strawn Jeffrey R, Poweleit Ethan A, Mills Jeffrey A, Schroeder Heidi K, Neptune Zoe A, Specht Ashley M, Farrow Jenni E, Zhang Xue, Martin Lisa J, Ramsey Laura B
Anxiety Disorders Research Program, Department of Psychiatry & Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH 45219, USA.
Cincinnati Children's Hospital Medical Center, Department of Pediatrics, Division of Clinical Pharmacology, Cincinnati, OH 45219, USA.
J Pers Med. 2021 Nov 12;11(11):1188. doi: 10.3390/jpm11111188.
Current pharmacologic treatments for pediatric anxiety disorders (e.g., selective serotonin reuptake inhibitors (SSRIs)) frequently use "one size fits all" dosing strategies based on average responses in clinical trials. However, for some SSRIs, including escitalopram, variation in CYP2C19 activity produces substantial variation in medication exposure (i.e., blood medication concentrations). This raises an important question: would refining current SSRI dosing strategies based on CYP2C19 phenotypes increase response and reduce side effect burden? To answer this question, we designed a randomized, double-blind trial of adolescents 12-17 years of age with generalized, separation, and/or social anxiety disorders (N = 132). Patients are randomized (1:1) to standard escitalopram dosing or dosing based on validated CYP2C19 phenotypes for escitalopram metabolism. Using this approach, we will determine whether pharmacogenetically-guided treatment-compared to standard dosing-produces faster and greater reduction in anxiety symptoms (i.e., response) and improves tolerability (e.g., decreased risk of treatment-related activation and weight gain). Secondarily, we will examine pharmacodynamic variants associated with treatment outcomes, thus enhancing clinicians' ability to predict response and tolerability. Ultimately, developing a strategy to optimize dosing for individual patients could accelerate response while decreasing side effects-an immediate benefit to patients and their families. ClinicalTrials.gov Identifier: NCT04623099.
目前用于治疗儿童焦虑症的药物疗法（例如，选择性5-羟色胺再摄取抑制剂（SSRIs））通常采用基于临床试验平均反应的“一刀切”给药策略。然而，对于某些SSRIs，包括艾司西酞普兰，CYP2C19活性的变化会导致药物暴露量（即血液中的药物浓度）产生显著差异。这就引出了一个重要问题：基于CYP2C19表型优化当前的SSRI给药策略是否会提高疗效并减轻副作用负担？为了回答这个问题，我们设计了一项针对12至17岁患有广泛性、分离性和/或社交焦虑症的青少年的随机双盲试验（N = 132）。患者被随机分组（1:1），分别接受标准的艾司西酞普兰给药或基于已验证的艾司西酞普兰代谢CYP2C19表型的给药。通过这种方法，我们将确定与标准给药相比，药物基因组学指导的治疗是否能更快、更显著地减轻焦虑症状（即疗效）并提高耐受性（例如，降低与治疗相关的激越和体重增加的风险）。其次，我们将研究与治疗结果相关的药效学变异，从而提高临床医生预测疗效和耐受性的能力。最终，制定一种针对个体患者优化给药的策略可以加快疗效，同时减少副作用，这将直接造福患者及其家人。ClinicalTrials.gov标识符：NCT04623099。
