Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants

Clin Pharmacol Ther. 2023 Jul;114(1):51-68. doi: 10.1002/cpt.2903. Epub 2023 May 30.


Serotonin reuptake inhibitor antidepressants, including selective serotonin reuptake inhibitors (SSRIs; i.e., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), serotonin and norepinephrine reuptake inhibitors (i.e., desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine), and serotonin modulators with SSRI-like properties (i.e., vilazodone and vortioxetine) are primary pharmacologic treatments for major depressive and anxiety disorders. Genetic variation in CYP2D6, CYP2C19, and CYP2B6 influences the metabolism of many of these antidepressants, which may potentially affect dosing, efficacy, and tolerability. In addition, the pharmacodynamic genes SLC6A4 (serotonin transporter) and HTR2A (serotonin-2A receptor) have been examined in relation to efficacy and side effect profiles of these drugs. This guideline updates and expands the 2015 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and SSRI dosing and summarizes the impact of CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes on antidepressant dosing, efficacy, and tolerability. We provide recommendations for using CYP2D6, CYP2C19, and CYP2B6 genotype results to help inform prescribing these antidepressants and describe the existing data for SLC6A4 and HTR2A, which do not support their clinical use in antidepressant prescribing.

Publication types

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

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Citalopram / therapeutic use
  • Cytochrome P-450 CYP2B6 / genetics
  • Cytochrome P-450 CYP2C19 / genetics
  • Cytochrome P-450 CYP2C19 / metabolism
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 CYP2D6 / metabolism
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / genetics
  • Genotype
  • Humans
  • Pharmacogenetics
  • Selective Serotonin Reuptake Inhibitors*
  • Serotonin
  • Serotonin Plasma Membrane Transport Proteins / genetics


  • Selective Serotonin Reuptake Inhibitors
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP2C19
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Antidepressive Agents
  • Citalopram
  • CYP2B6 protein, human
  • CYP2C19 protein, human
  • SLC6A4 protein, human