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

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. 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. 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). 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.