Effects of safinamide on non-motor, cognitive, and behavioral symptoms in fluctuating Parkinson's disease patients: a prospective longitudinal study

Introduction Parkinson's disease (PD) patients in chronic levodopa treatment may experience motor and non-motor fluctuations, which may affect their quality of life. Safinamide is a new monoamine oxidase B inhibitor, also exerting a non-dopaminergic effect, recently approved as add-on therapy in fluctuating PD patients. Methods We performed a longitudinal prospective study in a cohort of 20 fluctuating PD patients, to test whether safinamide 50 mg may improve non-motor, cognitive, and behavioral symptoms over a 6-month treatment period. At each timepoint, clinical features were assessed by means of validated PD-specific scales. Neuropsychological assessment was performed by exploring all five cognitive domains. Results Compared to baseline, significant improvement was found in PD patients at 6-month follow-up in items investigating interest (p = 0.02), motivation (p = 0.02), and urinary disturbances (p = 0.03). Moreover, neuropsychiatric assessment showed a significant decrease in fatigue and apathy scores (p = 0.02 and p = 0.01, respectively). Motor assessment revealed a significant reduction in the total wake-up time spent in OFF state (p = 0.01). Follow-up neuropsychological evaluation did not reveal any change compared to baseline. Conclusions Our data reveal that, along with motor fluctuation improvement, treatment with safinamide 50 mg may significantly decrease non-motor symptom burden in PD patients. Interestingly, non-dopaminergic mechanisms, such as glutamatergic overdrive, have been demonstrated to play a role in many pathways underlying these symptoms. Thus, we hypothesize that the neurotransmitter receptor-binding profile of safinamide may explain our findings.