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.