Influence of concomitant medications on the total clearance and the risk for supra-therapeutic plasma concentrations of Citalopram. A population-based cohort study.
BACKGROUND
The main objective of this study was to investigate the influence of the use of multiple medications and other risk factors on citalopram plasma concentrations.


METHODS
A retrospective cohort study with a naturalistic population of 957 patients for whom routine therapeutic drug monitoring (TDM) of citalopram had been requested between 2006 and 2013 was conducted.


RESULTS
Concomitant drugs inhibiting at least 2 different CYP subtypes involved in the metabolism of citalopram decreased statistically significantly the total clearance (Clt). Compared to younger patients over 64-year-old patients had on average a 4.5 times higher risk rate of supra-therapeutic plasma concentrations. However, binary logistic regression showed that age, sex and co-medication accounted only for 26% of the inter-individual variability of citalopram plasma concentrations.


CONCLUSIONS
Due to pharmacokinetic interactions, citalopram plasma concentrations are often higher than expected with a given dose. Especially in geriatric and often multimorbid patients who are usually prescribed high numbers of concomitant drugs and are at higher risk for adverse drug reactions (ADR), restriction of the maximal dose of citalopram is not sufficient to prevent supra-therapeutic plasma concentrations.
Department of Psychiatry and Psychotherapy, Clinical Psychopharmacology, University of Regensburg, Regensburg, Germany.
K
K
Wenzel-Seifert
Department of Psychiatry and Psychotherapy, Clinical Psychopharmacology, University of Regensburg, Regensburg, Germany.
R
R
Brandl
Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
C
C
Hiemke
Department of Psychiatry and Psychotherapy, Clinical Psychopharmacology, University of Regensburg, Regensburg, Germany.
E
E
Haen
D000328:Adult; D000367:Age Factors; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000493:pharmacokinetics*; D001837:Body Weights and Measures; D015283:Citalopram / Q000097:blood / Q000493:pharmacokinetics*; D065693:Cytochrome P-450 Enzyme Inducers / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D012737:Sex Factors
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D065693:Cytochrome P-450 Enzyme Inducers; D065607:Cytochrome P-450 Enzyme Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors