CYP2C19 genotype, physician prescribing pattern, and risk for long QT on serotonin selective reuptake inhibitors

Pharmacogenomics. 2019 Apr;20(5):343-351. doi: 10.2217/pgs-2018-0156. Epub 2019 Apr 15.

Abstract

Aim: To examine the impact of CYP2C19 genotype on selective serotonin reuptake inhibitor (SSRI) prescribing patterns. Patients & methods: Observational cohort containing 507 unique individuals receiving an SSRI prescription with CYP2C19 genotype already in their electronic medical record. Genotype was distributed as follows: n = 360 (71%) had no loss of function alleles, 136 (26.8%) had one loss of function allele and 11 (2.2%) had two loss of function alleles. Results & conclusion: For poor metabolizers exposed to sertraline, citalopram or escitalopram, providers changed prescribing patterns in response to alerts in the electronic medical record by either changing the drug, changing the dose or monitoring serial EKGs longitudinally. For intermediate metabolizers exposed to sertraline, citalopram or escitalopram, no alert was needed (mean QTc = 440.338 ms [SD = 31.1273] for CYP2C19*1/*1, mean QTc = 440.371 ms [SD = 29.2706] for CYP2C19*1/*2; p = 0.995).

Keywords: QT interval; QT prolongation; arrhythmia; citalopram; coronary artery disease; depression; escitalopram; pleiotropy; primary care; sertraline.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / metabolism
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Cohort Studies
  • Cytochrome P-450 CYP2C19 / genetics*
  • Cytochrome P-450 CYP2C19 / metabolism
  • Female
  • Genotype
  • Humans
  • Long QT Syndrome / chemically induced*
  • Long QT Syndrome / genetics*
  • Long QT Syndrome / metabolism
  • Male
  • Middle Aged
  • Pharmacogenomic Testing
  • Practice Patterns, Physicians'
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / metabolism
  • Selective Serotonin Reuptake Inhibitors / therapeutic use

Substances

  • Antidepressive Agents, Second-Generation
  • Serotonin Uptake Inhibitors
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19