Effects of Safinamide on Motor and Non-Motor Symptoms in Patients with Parkinson’s Disease and Motor Fluctuations

Introduction: Parkinson’s disease (PD) involves the progressive loss of dopaminergic neurons, leading to motor and non-motor symptoms that significantly impact patients’ quality of life. Safinamide modulates dopaminergic and glutamatergic systems, offering a promising treatment approach. Methods: This meta-analysis evaluated the efficacy of safinamide as an add-on therapy to levodopa for PD patients with motor fluctuations. Following PRISMA guidelines, literature searches were conducted in PubMed and Embase (2014–2022). Inclusion criteria were studies on adult PD patients receiving safinamide with levodopa. Outcomes included on-time without troublesome dyskinesia, off-time, UPDRS Part III motor scores, UPDRS Part II activities of daily living scores, PDQ-39 emotional well-being, and GRID-HAMD scores. Results: Among thirteen eligible studies, safinamide significantly improved on-time without troublesome dyskinesia at 100 mg/day (mean difference [MD]: −0.90; 95% CI: −1.12 to −0.67; p < 0.00001) and 50 mg/day (MD: −0.77; 95% CI: −1.21 to −0.34; p = 0.0005) compared to placebo. It also reduced off-time (100 mg/day: MD: −0.94; 95% CI: −1.19 to −0.70; p < 0.00001; 50 mg/day: MD: −0.72; 95% CI: −1.03 to −0.41; p < 0.00001) and improved UPDRS-III motor scores (100 mg/day: MD: −3.01; 95% CI: −4.15 to −1.86; p < 0.00001; 50 mg/day: MD: −2.93; 95% CI: −5.14 to −0.71; p = 0.001). Mood improvements were noted in PDQ-39 emotional well-being scores (MD: −5.22; 95% CI: −6.90 to −3.54) and GRID-HAMD scores (MD: −0.60; 95% CI: −0.95 to −0.25; p = 0.0009). Safinamide also positively affected pain (RR: 1.10; 95% CI: 1.03 to 1.18). Conclusion: Compared to placebo, safinamide significantly benefits motor and non-motor symptoms in PD patients, but further research is necessary to fully explore its therapeutic potential.