title: Lack of adverse interactions between concomitantly administered selegiline and citalopram.
abstract: We have evaluated the risk for pharmacokinetic and/or pharmacodynamic interactions of concomitantly administered selegiline, a selective monoamine oxidase type B inhibitor, and citalopram, a widely used selective serotonin uptake inhibitor antidepressant. Two parallel groups of healthy volunteers received 20 mg of citalopram (n = 12) or placebo (n = 6) once daily for 10 days in a randomized, double-blind fashion, followed by concomitant selegiline 10 mg once daily for 4 days. The safety of this drug combination was assessed by measurements of blood pressure, heart rate, body temperature, and inquiries for adverse events. Blood samples were taken for the analysis of serum concentrations of both study drugs and their metabolites and plasma prolactin, adrenaline, noradrenaline, and 3,4-dihydroxyphenylglycol (DHPG); urinary excretion of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were assessed. After a 5-week washout, the 12 subjects who took citalopram in the first part of the study received 10 mg of selegiline once daily for 4 days to compare the pharmacokinetics of selegiline with and without concomitant citalopram. The safety analysis showed no significant differences in vital signs or the frequency of adverse events between the study groups. Plasma prolactin concentrations were increased by 40% after 10 days' treatment with citalopram (p = 0.03); this was not potentiated by concomitantly administered selegiline. The comparison of plasma concentrations of noradrenaline, adrenaline, and DHPG and the amount of serotonin and 5-HIAA excreted into urine between the study groups indicated no signs of subclinical pharmacodynamic interaction between selegiline and citalopram. The relative bioavailability of selegiline was slightly reduced (by 29%; p = 0.008) when citalopram was coadministered compared with selegiline alone. However, no indication of a pharmacokinetic interaction was found in the analysis of serum concentrations of the three main metabolites of selegiline. The pharmacokinetics of citalopram remained unaffected by concomitant selegiline. The present results indicate lack of clinically relevant pharmacodynamic or pharmacokinetic interactions between selegiline and citalopram.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Laine
authors.forename: M
authors.initials: M
authors.lastname: Anttila
authors.forename: E
authors.initials: E
authors.lastname: Heinonen
authors.forename: A
authors.initials: A
authors.lastname: Helminen
authors.forename: R
authors.initials: R
authors.lastname: Huupponen
authors.forename: O
authors.initials: O
authors.lastname: Mäki-Ikola
authors.forename: K
authors.initials: K
authors.lastname: Reinikainen
authors.forename: M
authors.initials: M
authors.lastname: Scheinin
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015283:Citalopram / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004837:Epinephrine / Q000097:blood; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology*; D009284:Naphthols / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D010919:Placebos; D011388:Prolactin / Q000097:blood; D011409:Propylene Glycols / Q000097:blood; D012642:Selegiline / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012701:Serotonin / Q000652:urine; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D004837:Epinephrine; D006897:Hydroxyindoleacetic Acid; D008996:Monoamine Oxidase Inhibitors; D009284:Naphthols; D009638:Norepinephrine; D010919:Placebos; D011388:Prolactin; D011409:Propylene Glycols; D012642:Selegiline; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C056310:1-((3-hydroxy-4-methoxy)-1-naphthoxy)-2,3-propanediol