Serotonin Toxicity Association with Concomitant Antidepressants and Rasagiline Treatment: Retrospective Study ( STACCATO )

Background The serotonin toxicity syndrome ( STS ) is a potential risk with concurrent use of the monoamine oxidase type‐B inhibitor rasagiline and antidepressants. Objective To assess systematically the occurrence of STS in patients with Parkinson disease ( PD ) treated with rasagiline plus antidepressants (R+ ATD ), rasagiline without antidepressants (R), or antidepressants plus anti‐ PD dopaminergic medications ( ATD ) other than either rasagiline or selegiline. Methods A phase IV multicenter retrospective cohort study was conducted of patients with PD who began receiving R+ ATD , R, or ATD between September 1, 2006, and December 31, 2008. Medical records were reviewed for patient demographics, treatment details, and hospitalizations/emergency department ( ED ) visits. An adjudication committee independently reviewed records to verify case ascertainment and used the Hunter Serotonin Toxicity Criteria for case definition. Outcome variables were analyzed by descriptive statistics. Results A total of 1504 patients with PD (471 with R+ ATD ; 511 with R; and 525 with ATD ) were enrolled from 37 sites. In the R+ ATD and ATD groups, selective serotonin reuptake inhibitors ( SSRI s) were most frequently used (74.5% and 77%, respectively). In the R+ ATD and ATD groups, mean duration of antidepressant use (tricyclic, SSRI , and other) were 50.5–53.5 weeks and 51.7–80.9 weeks, respectively. Overall, 195 patients (13%) from all three groups had one or more hospitalization/ ED visits. No cases of STS were identified in any group. Conclusions In this large multicenter retrospective cohort study, concurrent administration of R+ATD was not associated with STS . The findings of this phase IV study expand the drug interaction and pharmacovigilance safety awareness for the use of antidepressants in patients with PD .