Phenotype-driven approach for safinamide use in Parkinson’s disease

Parkinson’s disease (PD) is now recognized as a multisystem neurodegenerative disorder marked by the progressive disintegration of large-scale functional networks in the brain, a phenomenon termed connectomopathy. The clinical heterogeneity of PD reflects the distinct patterns of neuronal ensemble involvement in individual patients, contributing to both motor and non-motor symptoms. This perspective highlights the necessity of a phenotype-driven approach when selecting anti-Parkinsonian therapies. This article examines the role of safinamide, a drug with dual mechanisms of action: reversible inhibition of monoamine oxidase-B and anti-glutamatergic properties, within the framework of personalized PD management. Clinical case analyses demonstrate that safinamide prolongs the «on» period without a significant increase in dyskinesias and provides additional therapeutic benefits for non-motor symptoms, including chronic pain, depression, and sleep disturbances.