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Front Pharmacol. 2019 Feb 19;10:99. doi: 10.3389/fphar.2019.00099. eCollection 2019.

Influence of CYP2C19 Metabolizer Status on Escitalopram/Citalopram Tolerability and Response in Youth With Anxiety and Depressive Disorders.

Author information

1
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
2
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
3
Division of Research in Patient Services, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
4
Division of Patient Services, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
5
Anxiety Disorders Research Program, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, United States.
6
Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.

Abstract

In pediatric patients, the selective serotonin reuptake inhibitors (SSRIs) escitalopram and citalopram (es/citalopram) are commonly prescribed for anxiety and depressive disorders. However, pharmacogenetic studies examining CYP2C19 metabolizer status and es/citalopram treatment outcomes have largely focused on adults. We report a retrospective study of electronic medical record data from 263 youth < 19 years of age with anxiety and/or depressive disorders prescribed escitalopram or citalopram who underwent routine clinical CYP2C19 genotyping. Slower CYP2C19 metabolizers experienced more untoward effects than faster metabolizers (p = 0.015), including activation symptoms (p = 0.029) and had more rapid weight gain (p = 0.018). A larger proportion of slower metabolizers discontinued treatment with es/citalopram than normal metabolizers (p = 0.007). Meanwhile, faster metabolizers responded more quickly to es/citalopram (p = 0.005) and trended toward less time spent in subsequent hospitalizations (p = 0.06). These results highlight a disparity in treatment outcomes with es/citalopram treatment in youth with anxiety and/or depressive disorders when standardized dosing strategies were used without consideration of CYP2C19 metabolizer status. Larger, prospective trials are warranted to assess whether tailored dosing of es/citalopram based on CYP2C19 metabolizer status improves treatment outcomes in this patient population.

KEYWORDS:

CYP2C19; SSRI (selective serotonin reuptake inhibitor); antidepressant; anxiety disorders; citalopram; depressive disorder; escitalopram; pharmacogenetics

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