LACK OF ADVERSE INTERACTIONS BETWEEN CONCOMITANTLY ADMINISTERED SELEGILINE AND CITALOPRAM

We have evaluated the risk for pharmacokinetic and/or pharmacodynamic interactions of concomitantly administered selegiline, a selective mon oamine oxidase type B inhibitor, and citalopram, a widely used selecti ve serotonin uptake inhibitor antidepressant. Two par allel 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, fo llowed by concomitant selegiline 10 mg once daily for 4 days, The safe ty of this drug combination was assessed by measurements of blood pres sure, heart rate, body temperature, and inquiries for adverse events. Blood samples were taken for the analysis of serum concentrations of b oth study drugs and their metabolites and plasma prolactin, adrenaline , noradrenaline, and 3,4-dihydroxyphenylglycol (DHPG); urinary excreti on of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were assessed. After a 5-week washout, the 12 subjects who took citalopram in the fi rst part of the study received 10 mg of selegiline once daily for 4 da ys to compare the pharmacokinetics of selegiline with and without conc omitant citalopram. The safety analysis showed no significant differen ces in vital signs or the frequency of adverse events between the stud y groups, Plasma prolactin concentrations were increased by 40% after 10 days' treatment with citalopram (p = 0.03); this was not potentiate d by concomitantly administered selegiline. The comparison of plasma c oncentrations of noradrenaline, adrenaline, and DHPG and the amount of serotonin and 5-HIAA excreted into urine between the study groups ind icated no signs of subclinical pharmacodynamic interaction between sel egiline and citalopram. The relative bioavailability of selegiline was slightly reduced (by 29%; p = 0.008) when citalopram was coadminister ed compared with selegiline alone. However, no indication of a pharmac okinetic 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 pharma cokinetic interactions between selegiline and citalopram.