title: Long-Term Effects of Safinamide on Dyskinesia in Mid- to Late-Stage Parkinson's Disease: A Post-Hoc Analysis.
abstract: BACKGROUND
  Safinamide is a novel α-aminoamide with dopaminergic and non-dopaminergic properties developed as adjunctive therapy for patients with PD. Results from a 24-month double-blind controlled study suggested that as add-on to levodopa (and other PD medications) the benefits of safinamide on dyskinesia may be related to severity of dyskinesia at baseline.
  
  
  OBJECTIVE
  This post-hoc analysis further characterized the effects of safinamide on dyskinesia in mid- to late-stage PD patients.
  
  
  METHODS
  Patients were stratified by the presence or absence of dyskinesia at baseline, and by whether or not the dose of levodopa had been changed during the 24-month treatment period. Differences between safinamide and placebo were evaluated using the Wilcoxon rank-sum test.
  
  
  RESULTS
  For the overall treated population (with or without baseline dyskinesia), safinamide 100 mg/day significantly improved the dyskinesia rating scale score, compared with placebo, in the subgroup of patients with no change in levodopa dose (p = 0.0488). For patients with baseline dyskinesia, improvements over placebo were also significant (p = 0.0153) in patients with or without changes in levodopa dose, and nearly significant (p = 0.0546) in patients with no change in levodopa dose, suggesting that these improvements were not due to levodopa dose reductions.
  
  
  CONCLUSIONS
  While no statistically significant difference in mean DRS scores was seen between safinamide and placebo in the original study population, the present post-hoc analysis helps to provide a meaningful interpretation of the long-term effects of safinamide on dyskinesia. These results may be related to safinamide state- and use-dependent inhibition of sodium channels and stimulated glutamate release, and are unlikely due to reduced dopaminergic stimulation.
authors.affiliation: Department of Medical, Zambon SpA, Bresso, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cattaneo
authors.affiliation: Department of Medical, Zambon SpA, Bresso, Italy.
authors.forename: R La
authors.initials: RL
authors.lastname: Ferla
authors.affiliation: Department of Clinical Science and Community, Section of Medical Statistics and Biometry "GA Maccacaro", University of Milan, Italy.
authors.forename: Erminio
authors.initials: E
authors.lastname: Bonizzoni
authors.affiliation: Department of R&D, Zambon SpA, Bresso, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sardina
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001596:Benzylamines / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D020820:Dyskinesias / Q000188:drug therapy* / Q000209:etiology; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D001596:Benzylamines; D007980:Levodopa; C092797:safinamide; D000409:Alanine
keywords: Parkinson’s disease; dyskinesia; levodopa; safinamide