IntroductionSleep problems commonly occur in Parkinson's disease (PD) and significantly affect patients' quality of life. A possible effect on subjective sleep disturbances of monoamine oxidase-B inhibitors (MAOB-Is) has been described. MethodsThis prospective, observational, single-centre study involved 45 fluctuating PD patients complaining sleep problems as documented by the PD Sleep Scale -2nd version (PDSS-2 ≥18) starting rasagiline 1 mg/daily or safinamide 100 mg/daily, according to common clinical practice, and maintaining antiparkinsonian therapy unchanged. Polysomnography (PSG), sleep questionnaires (PDSS-2, Epworth Sleepiness Scale - ESS), and motor function were evaluated at baseline (T0) and after 4 months of treatment (T1). ResultsSafinamide was prescribed in thirty patients and rasagiline in fifteen patients. Both drugs induced a significant improvement in Movement Disorder Society Unified PD Rating Scale III scores. Patients treated with rasagiline showed a significant increase in stage 1 (N1) Non-REM sleep compared to T0, with no significant effects on sleep scales. Patients treated with safinamide showed a significant increase in stage 3 of Non-REM sleep and sleep efficiency and a reduction in the rate of periodic limb movements, matching a significant reduction in PDSS-2 and ESS scales compared to T0. ConclusionThis study showed that safinamide, in addition to having a significant effect on PD motor symptoms, like the other MAOB-Is, may exert a specific beneficial effect on subjective and objective sleep, probably driven by its dual mechanism of action, which involves both dopaminergic and glutamatergic neurotransmission.