title: Effect of proton pump inhibitors on the serum concentrations of the selective serotonin reuptake inhibitors citalopram, escitalopram, and sertraline.
abstract: BACKGROUND
  The selective serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram, and sertraline are all metabolized by the cytochrome P-450 isoenzyme CYP2C19, which is inhibited by the proton pump inhibitors (PPIs) omeprazole, esomeprazole, lansoprazole, and pantoprazole. The aim of the present study was to evaluate the effect of these PPIs on the serum concentrations of citalopram, escitalopram, and sertraline.
  
  
  METHODS
  Serum concentrations from patients treated with citalopram, escitalopram, or sertraline were obtained from a routine therapeutic drug monitoring database, and samples from subjects concomitantly using PPIs were identified. Dose-adjusted SSRI serum concentrations were calculated to compare data from those treated and those not treated with PPIs.
  
  
  RESULTS
  Citalopram concentrations were significantly higher in patients treated with omeprazole (+35.3%; P < 0.001), esomeprazole (+32.8%; P < 0.001), and lansoprazole (+14.7%; P = 0.043). Escitalopram concentrations were significantly higher in patients treated with omeprazole (+93.9%; P < 0.001), esomeprazole (+81.8%; P < 0.001), lansoprazole (+20.1%; P = 0.008), and pantoprazole (+21.6%; P = 0.002). Sertraline concentrations were significantly higher in patients treated with esomeprazole (+38.5%; P = 0.0014).
  
  
  CONCLUSIONS
  The effect of comedication with PPIs on the serum concentration of SSRIs is more pronounced for omeprazole and esomeprazole than for lansoprazole and pantoprazole, and escitalopram is affected to a greater extent than are citalopram and sertraline. When omeprazole or esomeprazole are used in combination with escitalopram, a 50% dose reduction of the latter should be considered.
authors.affiliation: *Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim; †Department of Pharmaceutical Bioscience, School of Pharmacy, University of Oslo; ‡Department of Anaesthesiology and Critical Care, St. Olav University Hospital; §Department of Circulation and Medical Imaging, Norwegian University of Science and Technology; and ¶Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gjestad
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Westin
authors.forename: Eirik
authors.initials: E
authors.lastname: Skogvoll
authors.forename: Olav
authors.initials: O
authors.lastname: Spigset
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015283:Citalopram / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D020280:Sertraline / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D015283:Citalopram; D054328:Proton Pump Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline