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<p>We evaluated the effect of CYP2C19 genotype on SSRI response in 114,627 research participants. We graded metabolizer status (0 for ultrarapid metabolizers to 4 for poor metabolizers), and regressed drug response outcomes on these grades. Among participants taking escitalopram or citalopram, slower metabolizers experienced side effects significantly more often than faster metabolizers (OR = 1.04 per grade, 95%CI = [1.02-1.06] and OR = 1.05 per grade, 95%CI = [1.02-1.07]) and were more likely to discontinue treatment due to side effects (OR = 1.05, 95%CI = [1.03-1.08], e.g. 29.7% of poor vs. 21.6% of ultrarapid metabolizers, and OR = 1.07, 95%CI = [1.04-1.11], e.g. 25.7% vs. 20.2%). Slower metabolizers taking escitalopram were more likely to suffer from sleep problems and sexual problems. Slower metabolizers taking sertraline reported tremor more often than faster metabolizers. Overall, we find substantial differences in side effect risk with different CYP2C19 genotypes, supporting the notion that individuals seeking depression treatment may benefit from pharmacogenetic-guided treatment selection to minimize side effects and reduce discontinuations.</p>

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Large-scale analysis demonstrates the influence of CYP2C19 genotype on specific SSRI side effects

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Chris Eijsbouts,
  • Yunxuan Jiang,
  • James R. Ashenhurst,
  • Julie M. Granka,
  • Stella Aslibekyan,
  • Robert K. Bell,
  • Zayn Cochinwala,
  • Sayantan Das,
  • Kahsaia de Brito,
  • Emily DelloRusso,
  • Devika Dhamija,
  • Payam Dibaeinia,
  • Sarah L. Elson,
  • Nicholas Eriksson,
  • Shirin Fuller,
  • Chris German,
  • Larry Hengl,
  • Barry Hicks,
  • David A. Hinds,
  • Michael V. Holmes,
  • M. Reza Jabalameli,
  • Ethan M. Jewett,
  • Matt Kmiecik,
  • Katelyn Kukar Bond,
  • Alan Kwong,
  • Keng-Han Lin,
  • Yanyu Liang,
  • Aly Khan,
  • Matthew H. McIntyre,
  • Alex Moran,
  • Carrie Northover,
  • Jared O’Connell,
  • Steve Pitts,
  • Shubham Saini,
  • Anjali J. Shastri,
  • Jingchunzi Shi,
  • Suyash Shringarpure,
  • Teague Sterling,
  • Qiaojuan Jane Su,
  • Joyce Y. Tung,
  • Vinh Tran,
  • Xin Wang,
  • Catherine H. Weldon,
  • Wanwan Xu,
  • Steven Pitts,
  • Adam Auton,
  • Noura S. Abul-Husn,
  • Alison Chubb,
  • R. Ryanne Wu

摘要

We evaluated the effect of CYP2C19 genotype on SSRI response in 114,627 research participants. We graded metabolizer status (0 for ultrarapid metabolizers to 4 for poor metabolizers), and regressed drug response outcomes on these grades. Among participants taking escitalopram or citalopram, slower metabolizers experienced side effects significantly more often than faster metabolizers (OR = 1.04 per grade, 95%CI = [1.02-1.06] and OR = 1.05 per grade, 95%CI = [1.02-1.07]) and were more likely to discontinue treatment due to side effects (OR = 1.05, 95%CI = [1.03-1.08], e.g. 29.7% of poor vs. 21.6% of ultrarapid metabolizers, and OR = 1.07, 95%CI = [1.04-1.11], e.g. 25.7% vs. 20.2%). Slower metabolizers taking escitalopram were more likely to suffer from sleep problems and sexual problems. Slower metabolizers taking sertraline reported tremor more often than faster metabolizers. Overall, we find substantial differences in side effect risk with different CYP2C19 genotypes, supporting the notion that individuals seeking depression treatment may benefit from pharmacogenetic-guided treatment selection to minimize side effects and reduce discontinuations.