Safinamide is a monoamine-oxidase-B inhibitor with peculiar features. At the dose of 100 mg/day, safinamide stimulates dopaminergic transmission and reduces glutamatergic transmission. Here, we investigated the effects of safinamide 100 mg on executive functions at the end of levodopa dose in fluctuating Parkinson’s disease (PD) patients. Thirty-two fluctuating PD patients were submitted at baseline (V1) to the UPDRS-III, the Frontal Assessment Battery (FAB) and the Stroop-Word-Color-Test (SWCT) at the end of levodopa dose. Safinamide was then added to the original therapy. After 12 weeks of treatment, patients underwent the final visit (V2), including the UPDRS-III, the FAB and the SWCT with the same daily time schedule as V1. Treatment with safinamide was associated with significant increases of the total FAB score, SWCT-interference time score and UPDRS-III score. Within FAB subdomains, add-on with safinamide significantly increased motor programming and increased mental flexibility and inhibitory control scores. The results of this exploratory study show that add-on with safinamide improves executive functions at the end of levodopa dose in fluctuating PD patients. In particular, attention and inhibition of cognitive interference were significantly ameliorated by add-on with safinamide, suggesting increased modulatory performances of prefrontal cortical pathways. If confirmed by future research on larger cohorts and under controlled conditions, the present results may represent the basis for a novel indication for the use of safinamide in fluctuating PD patients.
