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.

Escitalopram population pharmacokinetics in people living with human immunodeficiency virus and in the psychiatric population: Drug–drug interactions and probability of target attainment

“…These comedications were all represented by proton‐pump inhibitors. Although several publications already mentioned this interaction, its magnitude varies from weak to moderate . The decrease of 19% in escitalopram clearance when coadministered with at least 1 CYP2C19 inhibitor found in our study is in good agreement with a prediction based on theoretical considerations provided in the DDI‐predictor tool .…”

“…As strong perpetrators influenced only moderately escitalopram exposure, the effect of weak perpetrators was supposed to be clinically nonsignificant and was therefore not included in the analysis. Since several studies have evaluated the effect of proton‐pump inhibitors on escitalopram pharmacokinetics, they were included in the analysis as moderate CYP2C19 inhibitors . Comedications including ARTs were classified as moderate CYP2C19 inhibitors (12% of the patients) or inducers (10%), strong CYP3A4 inhibitors (16%) or inducers (2%), strong CYP2D6 inhibitors (2%) as well as p‐glycoprotein inhibitors (15%), according to the lists published by the Food and Drug Administration and the University Hospital of Geneva .…”

Quercetin and Ellagic Acid in Gastric Ulcer Prevention: An Integrated Scheme of the Potential Mechanisms of Action From in Vivo Study

“…There are documents from studies both in vitro and in vivo indicating that Omeprazole can inhibit the activity of cytochrome P-450 isoenzyme CYP2C19 (CYP2C19). It has been shown that the selective ST reuptake inhibitors Citalopram, Escitalopram, and Sertraline are all metabolized by CYP2C19 [56]. This explains the observed elevation in serum ST level on Omeprazole administration.…”

Treatment With Antipsychotics in Pregnancy: Changes in Drug Disposition

“…Ideally, this interval should have been standardized to 12 h, and all values calculated to such using drug‐specific elimination half‐lives, as in a previous publication from our group 29. However, information for calculating the time interval was often missing on the requisition form, and excluding all such measurements would result in loss of precious data.…”