Effects of safinamide on pain in patients with fluctuating Parkinson's disease

Abstract

Background: Non-motor symptoms (NMS) are integral to Parkinson's Disease (PD) and management remains a challenge. Safinamide is a novel molecule in relation to addressing NMS due to its multifocal mechanism of action with both dopaminergic and nondopaminergic properties. Objective: To investigate the efficacy of safinamide on NMS and its burden in PD patients with motor fluctuations after 6 months of treatment. Methods: This observational, multicenter, open-label, pilot study assessed a wide range of NMS using the following rating scales, NMSS (non-motor symptom scale), KPPS (King's PD pain scale), HADS (hospital anxiety and depression scale), PDQ-8 (Parkinson's disease quality of life questionnaire), and PDSS-2 (Parkinson's disease sleep scale), EuroQol-5D 3 level version (EQ-5D-3L), CGI-I (clinical global impression of improvement), and PGI-C (patient global impression of change). Motor examination using UPDRS part III (Unified Parkinson's disease rating scale, motor examination), UPDRS IV (complications of therapy) and Hoehn and Yahr staging were also obtained.Results: 27 patients were included in the analysis and were evaluated at baseline and ≥ 6 months after safinamide treatment. 26 patients had a daily maintenance dose of 100 mg and 1 patient a daily dose of 50 mg. Significant improvements in UPDRS IV, KPPS item 5 (region-specific "off" dystonia), KPPS domain 3 (items 4-6, fluctuation related pain) and KPPS total score were observed after treatment with safinamide, while maintaining stable dopaminergic medication. No statistically significant differences were found in NMSS, HADS, PDSS-2, EQ-5D-3L, and PDQ-8 after treatment. Conclusions:Our results suggest that safinamide may have a beneficial effect on pain, a key unmet need in fluctuating PD patients.

Effects of MAO-B inhibitors on non-motor symptoms and quality of life in Parkinson’s disease: A systematic review

“…In a multicenter, double-blind, placebo-controlled RCT 38 and two open-label prospective studies 43 , 44 , safinamide 100 mg for advanced PD patients did not significantly ameliorate depression at 6 months. However, in the Study 016 and its extension study (Study 018), significant benefits on the Hamilton Depression Scale (HAMD) and PDQ-39 emotional well-being subscore over placebo were observed with safinamide 100 mg but not with the 50 mg dose 37 , 39 .…”

“…All the studies of safinamide enrolled advanced PD patients 37 – 46 except for one study for those with high non-motor burden (defined as the NMS Scale (NMSS) ≥ 40) 25 . RCTs and open-label studies using safinamide 100 mg reported positive or negative QOL outcomes with safinamide 25 , 37 – 40 , 42 , 43 , 45 , 46 , whereas all the studies using safinamide 50 mg reported negative outcomes 37 , 39 , 40 , 44 . Based on the PDQ-39 outcomes from the RCTs, effect sizes for safinamide 100 mg and 50 mg were small (0.22–0.23) and trivial (0.11–0.15), respectively.…”

“…The Study 016, its post hoc analysis, and an open-label study observed significant improvement in the PDQ-39 emotional well-being subscore 37 , 48 . However, none of the two open-label prospective studies found significant benefits of safinamide on anxiety 43 – 45 .…”

“…Six open-label studies have reported the impact of safinamide on sleep disturbances 25 , 26 , 43 – 45 , 57 . Most studies employed the PDSS-2 and ESS; however, the outcomes were inconsistent.…”

“…Furthermore, small open-label studies and post hoc analyses of large RCTs for advanced PD patients support the efficacy of safinamide 100 mg on pain 25 , 46 , 60 . Two open-label studies reported detailed outcomes based on the King’s PD pain scale, suggesting that safinamide 100 mg improves fluctuation-related pain 43 , 61 . Collectively, safinamide 100 mg possibly ameliorates pain, especially fluctuation-related pain, with trivial to small effect size (0.16–0.41).…”