Objectives: To evaluate the potential of pharmacodynamic and pharmacokinetic interactions of a concomitantly administered monoamine oxidase (MAO) type B inhibitor rasagiline and a selective serotonin reuptake inhibitor (SSRI) escitalopram.
Methods: Twelve healthy male volunteers received a 10-day regimen of rasagiline 1mg daily, followed by concomitant rasagiline 1mg and escitalopram 10mg daily for 7 days.
Results: We found that the drug combination was generally well tolerated, and there were no signs of central nervous system hyperexcitation or changes in the subjects' vital signs. The reported adverse effects were mainly mild or moderate, and typical for SSRIs. The MAO-A-dependent catecholamine metabolite DHPG levels did not change significantly during the study suggesting that rasagiline's MAO-B selectivity was preserved. The plasma monoamine concentrations indicated no subclinical signs of interaction. As expected, the whole blood serotonin was significantly reduced by escitalopram but unaffected by rasagiline. Rasagiline AUC was increased by 42% (p<0.0001) and the weight-adjusted apparent oral clearance was reduced by 35% (p=0.0009) after 7 days' concomitant escitalopram treatment. Escitalopram reduced the ratio of the AUC values of the main metabolite 1-aminoindan and rasagiline by about 23% (p=0.0079). There were no significant changes in the elimination half-life, t(max) and C(max) of rasagiline.
Conclusions: These results suggest good tolerability of concomitant administration of rasagiline and escitalopram. However, other medications, diseases and aging may change the individual drug response and tolerability of concomitant rasagiline and escitalopram, e.g. in Parkinsonian patients, and thus careful monitoring is recommended when combining rasagiline and escitalopram.