Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized Trial
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/11/11/1188 |
| _version_ | 1797509758910988288 |
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| author | Jeffrey R. Strawn Ethan A. Poweleit Jeffrey A. Mills Heidi K. Schroeder Zoe A. Neptune Ashley M. Specht Jenni E. Farrow Xue Zhang Lisa J. Martin Laura B. Ramsey |
| author_facet | Jeffrey R. Strawn Ethan A. Poweleit Jeffrey A. Mills Heidi K. Schroeder Zoe A. Neptune Ashley M. Specht Jenni E. Farrow Xue Zhang Lisa J. Martin Laura B. Ramsey |
| author_sort | Jeffrey R. Strawn |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T05:22:17Z |
| format | Article |
| id | doaj.art-ffc9f63cbda640d6b0e82fab50b6edf4 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T05:22:17Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-ffc9f63cbda640d6b0e82fab50b6edf42023-11-22T23:59:13ZengMDPI AGJournal of Personalized Medicine2075-44262021-11-011111118810.3390/jpm11111188Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized TrialJeffrey R. Strawn0Ethan A. Poweleit1Jeffrey A. Mills2Heidi K. Schroeder3Zoe A. Neptune4Ashley M. Specht5Jenni E. Farrow6Xue Zhang7Lisa J. Martin8Laura B. Ramsey9Anxiety Disorders Research Program, Department of Psychiatry & Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH 45219, USACincinnati Children’s Hospital Medical Center, Department of Pediatrics, Division of Clinical Pharmacology, Cincinnati, OH 45219, USADepartment of Economics, Lindner College of Business, University of Cincinnati, Cincinnati, OH 45219, USAAnxiety Disorders Research Program, Department of Psychiatry & Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH 45219, USAAnxiety Disorders Research Program, Department of Psychiatry & Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH 45219, USAAnxiety Disorders Research Program, Department of Psychiatry & Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH 45219, USAAnxiety Disorders Research Program, Department of Psychiatry & Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH 45219, USACincinnati Children’s Hospital Medical Center, Division of Human Genetics, College of Medicine, University of Cincinnati, Cincinnati, OH 45219, USACincinnati Children’s Hospital Medical Center, Division of Human Genetics, College of Medicine, University of Cincinnati, Cincinnati, OH 45219, USACincinnati Children’s Hospital Medical Center, Department of Pediatrics, Division of Clinical Pharmacology, Cincinnati, OH 45219, USACurrent 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.https://www.mdpi.com/2075-4426/11/11/1188selective serotonin reuptake inhibitor (SSRI)anxiety disordersgeneralized anxiety disorder (GAD)pharmacogeneticCYP2C19pharmacokinetic |
| spellingShingle | Jeffrey R. Strawn Ethan A. Poweleit Jeffrey A. Mills Heidi K. Schroeder Zoe A. Neptune Ashley M. Specht Jenni E. Farrow Xue Zhang Lisa J. Martin Laura B. Ramsey Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized Trial Journal of Personalized Medicine selective serotonin reuptake inhibitor (SSRI) anxiety disorders generalized anxiety disorder (GAD) pharmacogenetic CYP2C19 pharmacokinetic |
| title | Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized Trial |
| title_full | Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized Trial |
| title_fullStr | Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized Trial |
| title_full_unstemmed | Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized Trial |
| title_short | Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized Trial |
| title_sort | pharmacogenetically guided escitalopram treatment for pediatric anxiety disorders protocol for a double blind randomized trial |
| topic | selective serotonin reuptake inhibitor (SSRI) anxiety disorders generalized anxiety disorder (GAD) pharmacogenetic CYP2C19 pharmacokinetic |
| url | https://www.mdpi.com/2075-4426/11/11/1188 |
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