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. 2015 Feb;37(1):90-7.
doi: 10.1097/FTD.0000000000000101.

Effect of Proton Pump Inhibitors on the Serum Concentrations of the Selective Serotonin Reuptake Inhibitors Citalopram, Escitalopram, and Sertraline

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Free PMC article

Effect of Proton Pump Inhibitors on the Serum Concentrations of the Selective Serotonin Reuptake Inhibitors Citalopram, Escitalopram, and Sertraline

Caroline Gjestad et al. Ther Drug Monit. .
Free PMC article

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.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Expected serum concentrations of citalopram (top panel), escitalopram (middle panel), and sertraline (lower panel) in women (left part) and men (right part) related to age, applying the model presented in Tables 2–4. As a comparison, the effect of esomeprazole (which was the only PPI significantly affecting the C/D ratio for both citalopram, escitalopram, and sertraline) is also shown. The shaded areas represent 95% confidence intervals. For citalopram and escitalopram, 100 nmol/L correspond to 32.5 ng/mL. For sertraline, 100 nmol/L correspond to 30.6 ng/mL.
FIGURE 2
FIGURE 2
Expected serum concentrations of citalopram (top panel), escitalopram (middle panel), and sertraline (lower panel) with 95% confidence intervals in men and women at 2 different ages during monotherapy and during comedication with PPIs, applying the model presented in Tables 2–4. The doses are set to 20 mg/d for citalopram, 10 mg/d for escitalopram, and 100 mg/d for sertraline.

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