Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers

J Clin Psychopharmacol. 2007 Feb;27(1):28-34. doi: 10.1097/00004714-200702000-00005.


This study is the first to directly compare the relative effects of duloxetine, escitalopram, and sertraline on the functional activity of the drug-metabolizing cytochrome P450 2D6 enzyme as assessed by changes in the pharmacokinetics of the cytochrome P450 2D6 model substrate drug, metoprolol. Single-dose pharmacokinetics of metoprolol were measured before and after 17 days of treatment with escitalopram 20 mg/d, duloxetine 60 mg/d, or sertraline 100 mg/d in young healthy male and female participants. The outcome measures were changes in metoprolol peak plasma levels, area under the plasma concentration-time curve, and clearance. The results were tested using paired t tests and independent t tests. The addition of each drug produced statistically significant changes in metoprolol pharmacokinetics. The rank order for the change in metoprolol area under the plasma concentration-time curve was duloxetine (180%) > escitalopram (89%) > sertraline (48% and 67%). Compared with sertraline, duloxetine produced statistically significantly larger changes in metoprolol pharmacokinetic parameters. The changes produced by escitalopram and sertraline were not statistically different.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacology*
  • Citalopram / administration & dosage
  • Citalopram / pharmacology*
  • Cytochrome P-450 CYP2D6 / drug effects*
  • Drug Interactions
  • Duloxetine Hydrochloride
  • Female
  • Humans
  • Male
  • Metoprolol / pharmacokinetics
  • Middle Aged
  • Reference Values
  • Sertraline / administration & dosage
  • Sertraline / pharmacology*
  • Single-Blind Method
  • Thiophenes / administration & dosage
  • Thiophenes / pharmacology*


  • Antidepressive Agents
  • Thiophenes
  • Citalopram
  • Duloxetine Hydrochloride
  • Cytochrome P-450 CYP2D6
  • Metoprolol
  • Sertraline