Incidence of Adverse Events in Individuals With Parkinson's Disease Treated With Monoamine Oxidase-B Inhibitor Safinamide as an Add-On to Levodopa Treatment: A Systematic Review and Meta-Analysis
Paula Abola, Niraj Adhikari
Introduction: Parkinson’s Disease (PD) is a disabling neurodegenerative disease. Its long-term highdose treatment with Levodopa increases the incidence of motor adverse events such as worsening of
PD and dyskinesia. These motor adverse events can be managed by monoamine oxidase-B (MAO-B)
inhibitors. Safinamide is used as an add-on to Levodopa because it is associated with fewer adverse
events than other MAO-B inhibitors. Methods: A systematic literature search and meta-analysis
were performed with randomized controlled trials that investigated the incidence of adverse events in
individuals with PD treated with Safinamide as an add-on to Levodopa treatment. The systematic search
was conducted in PubMed, Cochrane, and EBSCO databases. Methodological quality was assessed
using the Cochrane Grading Recommendations Assessment, Development and Evaluation approach.
Results: Five studies were included in our review. The incidence of adverse events and serious adverse
events in the Safinamide groups was like that in the placebo group (RR = 0.97, RR = 1, RR = 1.06, RR =
1.02). The incidence of worsening of PD was non-significantly lower in the Safinamide groups compared
to the placebo group (RR = 0.94, RR = 0.87). The incidence of dyskinesia was significantly higher in
the Safinamide groups compared to the placebo group (RR = 1.58, RR = 1.91). The incidence of back
pain was non-significantly lower in the Safinamide groups compared to the placebo group (RR = 0.60,
RR = 0.75). The incidence of headache was non-significantly higher in the 50 mg/day Safinamide group
compared to the placebo group (RR = 1.65), but in the 100 mg/day Safinamide group it was similar to
that in the placebo group (RR = 0.97). Conclusion: Safinamide as an add-on to Levodopa could lower
the incidence of worsening of PD and back pain, warranting further study. However, the effects of
Safinamide on the overall incidence of adverse events, serious adverse events, dyskinesia, and headache
are inconclusive due to study limitations.
