Effects of concomitant cytochrome P450 inhibitors on the metabolism of citalopram: Analysis of data from routine therapeutic drug monitoring (TDM)

Introduction: Due to a dose-dependent risk for QTc prolongations, torsade de pointes tachyarrhythmia and sudden death age-dependet maximal daily doses of citalopram are recommended. Concomitant drugs which prolong QTc or inhibit the metabolism of citalopram may increase the risk for adverse events. The aim of this study was to further analyse the influence of the concomitant medication on the total clearance (Clt)of citalopram. Method: Plasma concentrations of citalopram – a total of 959 – were collected during routine therapeutic drug monitoring (TDM). The means of Clt values of different subgroups of patients were compared by one-way analysis of covariance (ANCOVA) after controlling for potential confounders. Results: 1. Age over 65 years and female sex significantly reduced the Clt of citalopram by 25% and 16%, respectively. 2. About 40% of the patients younger than 65 years who were prescribed more than 40 mg of citalopram daily and 35% of the older patients with doses of more than 20 mg per day had plasma concentrations exceeding the therapeutic reference range of citalopram. 3. Only concomitant medications with inhibitors of at least two different CYP enzymes (CYP2C19, CYP2D6 or CYP3A4) reduced significantly the Clt of citalopram. Conclusion: For patients with risk factors as female sex, age over 65 years or concomitant medications including inhibitors of more than two CYP enzymes TDM is recommended to minimize the risk for adverse reactions of citalopram.