Skip Navigation
Skip to contents

JMD : Journal of Movement Disorders

OPEN ACCESS
SEARCH
Search
Advanced Search
mobile menu button

Articles

Page Path
HOME > J Mov Disord > Volume 18(4); 2025 > Article
Letter to the editor
 Efficacy of Safinamide in Early-Stage Parkinson’s Disease: A Pilot Evaluation of Motor Symptom Improvement
Yun Su Hwang1,2orcid, Han Uk Ryu1,2orcid, Sang Yeon Kim1,2orcid, Hyun Goo Kang1,2corresp_iconorcid
Journal of Movement Disorders 2025;18(4):393-395.
DOI: https://doi.org/10.14802/jmd.25176
Published online: August 19, 2025

1Department of Neurology, Jeonbuk National University Medical School and Hospital, Jeonju, Korea

2Research Institute of Clinical Medicine of Jeonbuk National University–Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea

Corresponding author: Hyun Goo Kang, MD, PhD Department of Neurology, Jeonbuk National University Medical School and Hospital, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea / Tel: +82-63-250-1590 / Fax: +82-63-251-9363 / E-mail: hgkang@jbnu.ac.kr
• Received: July 8, 2025   • Revised: August 1, 2025   • Accepted: August 13, 2025

Copyright © 2025 The Korean Movement Disorder Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

prev next
  • 3,510 Views
  • 122 Download
Full Article

Download PDF Download PDF

Dear Editor,
In Parkinson’s disease (PD), prioritizing early-stage interventions aimed at both improving motor symptom severity and delaying the onset of motor complications is crucial. Safinamide, a second-generation monoamine oxidase B inhibitor with antiglutamatergic properties, is approved as an adjunctive therapy for managing motor fluctuations in patients with advanced PD [1]. Safinamide has not been approved as an early adjunctive treatment for motor symptoms under the Movement Disorders Society (MDS) treatment guidelines [2]. Real-world data regarding its effects on individual motor symptoms (such as bradykinesia) remain scarce. We conducted a prospective, open-label, single-center study to evaluate the efficacy of 50 mg of safinamide in patients with early PD without motor complications (namely, “early-stage PD” in our study) and patients with PD with motor complications (namely, “advanced-stage PD”). Fifty-five patients were included, and 37 (19 patients with early-stage PD and 18 with advanced-stage PD) completed the 8-week evaluation (Supplementary Figure 1 in the online-only Data Supplement). The primary outcome was the change in motor symptom severity, which was presented as the MDS-Unified Parkinson’s Disease Rating Scale (UPDRS) Part 3 score after 8 weeks of safinamide treatment. Additional outcomes included changes in motor complications, which were presented as MDS-UPDRS Part 4 score; nonmotor nonmotor symptoms (NMSs), which were presented as the Korean version of the Non-Motor Symptom Scale (K-NMSS) score; neuropsychiatric symptoms, which were presented as the Neuropsychiatric Inventory Questionnaire (NPI-Q) score; and quality of life (QoL), which was presented as the Parkinson’s Disease Questionnaire–39 (PDQ-39) score. The methods used for statistical analyses are described in Supplementary Material (in the online-only Data Supplement).
The baseline characteristics of the participants are summarized in Supplementary Table 1 (in the online-only Data Supplement) (full evaluation-completer only), Supplementary Table 2 (in the online-only Data Supplement) (including dropout), and Supplementary Table 3 (in the online-only Data Supplement) (completer vs. dropout). The effects of safinamide on the MDS-UPDRS scores are summarized in Table 1. All participants were evaluated during their best “on” medication state at the assessment, ensuring optimal motor performance during the evaluation of the Part 3 scores. The MDS-UPDRS Part 3 scores significantly improved in all patients after safinamide add-on therapy (baseline: 35.95±12.24 vs. 8 weeks: 29.54±11.41; p<0.001). In addition, improvements were observed in facial expression and speech (p=0.005), bradykinesia (p<0.001) and gait and balance (p=0.035). The rigidity tended to improve, although not significantly (p=0.050). Both the early- and advanced-stage PD groups demonstrated significant improvements in the overall MDS-UPDRS Part 3 scores (p<0.05). In the early-stage group, improvements were observed in bradykinesia subscores (p=0.010) after Bonferroni correction. Comparative analysis of motor symptom severity between the two groups revealed no significant difference in the magnitude of improvement (Supplementary Table 4 in the online-only Data Supplement), even after adjusting for baseline differences between the groups. Motor complications (MDS-UPDRS Part 4 scores) improved in the advanced PD group (baseline: 5.83±2.62 vs. 8 weeks: 3.39±3.11; p=0.001), without worsening of dyskinesias (Table 1). No statistically significant changes were observed in NMSs (K-NMSS scores), neuropsychiatric symptoms (NPI-Q scores), or QoL (PDQ-39 scores) in either group (Supplementary Table 5 in the online-only Data Supplement), and the incidence of adverse events did not differ significantly between the groups (p>0.05) (Supplementary Table 6 in the online-only Data Supplement).
This study demonstrated that safinamide significantly improved both motor symptom severity and fluctuation in patients with PD. The effects on motor symptom severity were significant in patients with early-stage PD and did not differ from those in patients with advanced-stage PD. To date, the evidence supporting the use of safinamide as an adjunctive to levodopa for treatment of early-stage PD remains insufficient [2], with most clinical trials that focused on improving motor fluctuations revealing primary outcomes centered on reducing “off” periods [3]. Few studies regarding patients with early-stage PD without motor complications have been reported. The 015 study and its extension, the 017 study, evaluated the effects of adjunctive safinamide on monotherapy with dopamine agonists and demonstrated that 100 mg of safinamide significantly improved motor symptoms [4,5]. The patients in the current study were selected based on those prior findings [4,5], considering their potential effect on motor symptom severity. In patients with early-stage PD, safinamide was administered to improve motor symptom severity, whereas in patients with advanced-stage PD, it was administered to address motor symptom severity, motor complications, or both. Consequently, patients with early-stage PD, who were treated solely to improve motor symptom severity, may exhibit more significant improvements in certain subscores, such as bradykinesia. However, the total MDS-UPDRS Part 3 score significantly improved in both groups, although the difference in improvement was not significant. Interestingly, despite differences in disease duration and the presence of motor complications, baseline motor symptom severity (measured using the MDS-UPDRS Part 3) was comparable between the early- and advanced-stage groups. This may be because patients in the early-stage group were selectively enrolled based on clinically significant motor symptoms that warranted treatment, resulting in relatively high motor symptom severity scores even in the absence of motor complications.
Most previous trials used an increase in dose to 100 mg; however, only a 50 mg dose was used in the current study. As studies exploring the levodopa equivalent daily dose (LEDD) of safinamide have been limited to European populations [6], we plan to evaluate the effect of increasing the dose to 100 mg after 8 weeks in future studies and compare whether 50 or 100 mg doses achieved LEDD levels similar to those observed in Western populations.
In our study, the effects of safinamide on NMSs were inconclusive. Although there was a trend toward improvement in the K-NMSS and NPI-Q scores in patients with advanced PD, statistical significance was not achieved. Furthermore, some patients reported symptoms commonly associated with NMSs (including dizziness, nausea, decreased appetite, lethargy, and facial flushing) as adverse events, complicating the interpretation. As safinamide was primarily used to address motor symptoms and was not specifically targeted to treat NMSs, definitive conclusions regarding its effects on NMSs cannot be drawn from this study.
In terms of safety, no cases of exacerbated dyskinesia were reported in this study. One potential underlying mechanism of dyskinesia, involving the hyperpotentiation of postsynaptic glutamate receptors related to dopaminergic pulsatile stimulation, may be inhibited by the antiglutamate effect of safinamide [1,7]. Pharmacological treatment before the presentation of motor complications is crucial for delaying the onset of dyskinesia as much as possible. Although our findings indicate that safinamide may improve motor symptom severity in patients with early-stage PD, the long-term effects of its dual mechanisms of action on the progression of PD itself and the timing of motor complication occurrence have yet to be determined [4]. These issues, which remain key barriers to the approval of safinamide for treatment of early-stage PD [4,5], should be addressed through a double-blind, randomized controlled trial directly comparing safinamide with placebo.
However, it may be more beneficial to add safinamide rather than increasing the levodopa dose in patients with early PD who need more improvement in motor symptoms. This could reduce the risk of pulsatile dopamine receptor stimulation compared with that associated with increasing the levodopa dose. Therefore, the official approval of safinamide as an adjuvant therapeutic option for patients with early-stage PD would contribute to the diversity of treatment options [7].
This study demonstrated the potential effects of a 50 mg dose of safinamide on the severity of motor symptoms in patients with early-stage PD. However, the open-label observational design without a placebo arm represents a significant limitation of this study. To provide more robust evidence for early adjuvant therapy, well-designed randomized controlled trials with larger sample sizes are needed. These findings support further investigations of safinamide as a potential therapeutic option for patients with early-stage PD to address the unmet needs in early motor symptom management.
The online-only Data Supplement is available with this article at https://doi.org/10.14802/jmd.25176.

SUPPLEMENTARY MATERIAL

jmd-25176-Supplementary-Material.pdf

Supplementary Table 1.

Clinical characteristics of the study participants who completed 8 weeks of evaluation after safinamide add-on therapy
jmd-25176-Supplementary-Table-1.pdf

Supplementary Table 2.

Clinical characteristics of all patients with PD prescribed safinamide
jmd-25176-Supplementary-Table-2.pdf

Supplementary Table 3.

Comparison of baseline characteristics of participants completing the 8-week study and those who dropped out
jmd-25176-Supplementary-Table-3.pdf

Supplementary Table 4.

Comparison of the effect of safinamide on motor symptoms in patients with early- and advanced-stage PD
jmd-25176-Supplementary-Table-4.pdf

Supplementary Table 5.

Comparison of nonmotor symptoms, neuropsychiatric symptoms, and QoL at baseline and 8 weeks after safinamide add-on therapy
jmd-25176-Supplementary-Table-5.pdf

Supplementary Table 6.

Adverse events at 8 weeks after safinamide add-on therapy
jmd-25176-Supplementary-Table-6.pdf

Supplementary Figure 1.

Flowchart of the study. *overlapped between categories (n=1). PD, Parkinson’s disease.
jmd-25176-Supplementary-Fig-1.pdf

Ethics Statement

This study was conducted in accordance with the principles outlined in the Declaration of Helsinki (2013) and was approved by the Institutional Review Board (IRB) of Jeonbuk National University Hospital (IRB approval number: CUH IRB 2022-08-030-001). The trial was registered with the Clinical Research Information Service (cris.nih.go.kr; study number: KCT0008194) on February 2, 2023. Written informed consent for participating in this clinical trial was obtained from all the participants of the trial.

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

This study was supported by funds from the Biomedical Research Institute, Jeonbuk National University Hospital, and Eisai Korea, Inc. The funders of the study had no role in the conduct of the study or the submission of the manuscript for publication.

Acknowledgments

This study analyzed data from the MDS-UPDRS and NMSS, after obtaining permission from the International Parkinson and Movement Disorder Society (MDS), the copyright holder.

Author Contributions

Conceptualization: Yun Su Hwang. Data curation: Yun Su Hwang, Sang Yeon Kim. Formal analysis: Yun Su Hwang, Han Uk Ryu. Funding acquisition: Yun Su Hwang, Hyun Goo Kang. Investigation: Yun Su Hwang. Methodology: Yun Su Hwang. Project administration: Yun Su Hwang, Hyun Goo Kang. Resources: Yun Su Hwang. Software: Yun Su Hwang. Supervision: Yun Su Hwang, Hyung Goo Kang. Validation: Yun Su Hwang. Visualization: Hyun Goo Kang, Sang Yeon Kim. Writing—original draft: Yun Su Hwang. Writing—review & editing: Yun Su Hwang, Hyun Goo Kang.

Table 1.
Comparison of motor symptoms at baseline and 8 weeks after safinamide add-on therapy
All patients (n=37)
 Early-stage patients without motor complications (n=19)
 Advanced-stage patients with motor complications (n=18)
Baseline 8 weeks after safinamide p value Baseline 8 weeks after safinamide p value Baseline 8 weeks after safinamide p value
MDS-UPDRS Part 2 9.75±8.58 7.28±6.15 0.025* 7.68±5.23 6.37±5.89 0.100* 12.06±10.93 8.29±6.45 0.132*
MDS-UPDRS Part 3 35.95±12.24 29.54±11.41 <0.001 34.32±12.53 27.58±12.81 <0.001 37.67±12.05 31.61±9.65 0.001*
 Facial expression and speech 2.51±1.39 1.84±1.41 0.005*† 2.47±1.58 1.89±1.45 0.130*† 2.56±1.20 1.78±1.40 0.060*†
 Rigidity 3.65±3.15 2.62±2.82 0.050*† 3.11±2.47 1.68±1.53 0.100† 4.22±3.72 3.61±3.52 0.835*†
 Bradykinesia 21.35±6.37 18.43±6.54 <0.001*† 20.42±6.46 16.68±7.01 0.010† 22.33±6.30 20.28±5.61 0.335*†
 Gait and balance 3.22±2.49 2.41±1.99 0.035† 3.11±2.33 2.26±2.02 0.110† 3.33±2.70 2.56±2.01 0.600†
 Tremor 5.22±3.97 4.24±4.25 0.360† 5.21±3.79 5.05±4.88 >0.999† 5.22±4.26 3.39±3.40 0.255†
MDS-UPDRS Part 4 - - - - - - 5.83±2.62 3.39±3.11 0.001
 Dyskinesia - - - - - - 0.39±1.24 0.67±1.41 0.900*†
 Motor fluctuation - - - - - - 5.44±2.46 2.72±2.68 <0.001†

Values are presented as mean±standard deviation.

* due to non-normal distribution, analyzed using the Wilcoxon signed-rank test;

† adjusted for multiple comparisons within each scale.

MDS-UPDRS, Movement Disorders Society-Unified Parkinson’s Disease Rating Scale.

  • 1. Blair HA, Dhillon S. Safinamide: a review in Parkinson’s disease. CNS Drugs 2017;31:169–176.ArticlePubMedPDF
  • 2. Fox SH, Katzenschlager R, Lim SY, Barton B, de Bie RMA, Seppi K, et al. International Parkinson and movement disorder society evidence-based medicine review: update on treatments for the motor symptoms of Parkinson’s disease. Mov Disord 2018;33:1248–1266.ArticlePubMedPDF
  • 3. Giossi R, Carrara F, Mazzari M, Lo Re F, Senatore M, Schicchi A, et al. Overall efficacy and safety of safinamide in Parkinson’s disease: a systematic review and a meta-analysis. Clin Drug Investig 2021;41:321–339.ArticlePubMedPMCPDF
  • 4. Schapira AH, Stocchi F, Borgohain R, Onofrj M, Bhatt M, Lorenzana P, et al. Long-term efficacy and safety of safinamide as add-on therapy in early Parkinson’s disease. Eur J Neurol 2013;20:271–280.ArticlePubMed
  • 5. Stocchi F, Borgohain R, Onofrj M, Schapira AH, Bhatt M, Lucini V, et al. A randomized, double-blind, placebo-controlled trial of safinamide as addon therapy in early Parkinson’s disease patients. Mov Disord 2012;27:106–112.ArticlePubMedPDF
  • 6. Cilia R, Cereda E, Piatti M, Pilotto A, Magistrelli L, Golfrè Andreasi N, et al. Levodopa equivalent dose of safinamide: a multicenter, longitudinal, case-control study. Mov Disord Clin Pract 2023;10:625–635.ArticlePubMedPMCPDF
  • 7. Thanvi BR, Lo TC. Long term motor complications of levodopa: clinical features, mechanisms, and management strategies. Postgrad Med J 2004;80:452–458.ArticlePubMedPMCPDF

Figure & Data

References

    Citations

    Citations to this article as recorded by  

      Comments on this article

      Add a comment
      Related articles
      Efficacy of Safinamide in Early-Stage Parkinson’s Disease: A Pilot Evaluation of Motor Symptom Improvement
      Efficacy of Safinamide in Early-Stage Parkinson’s Disease: A Pilot Evaluation of Motor Symptom Improvement
      All patients (n=37)
      		 Early-stage patients without motor complications (n=19)
      		 Advanced-stage patients with motor complications (n=18)
      Baseline 8 weeks after safinamide p value Baseline 8 weeks after safinamide p value Baseline 8 weeks after safinamide p value
      MDS-UPDRS Part 2 9.75±8.58 7.28±6.15 0.025* 7.68±5.23 6.37±5.89 0.100* 12.06±10.93 8.29±6.45 0.132*
      MDS-UPDRS Part 3 35.95±12.24 29.54±11.41 <0.001 34.32±12.53 27.58±12.81 <0.001 37.67±12.05 31.61±9.65 0.001*
       Facial expression and speech 2.51±1.39 1.84±1.41 0.005*† 2.47±1.58 1.89±1.45 0.130*† 2.56±1.20 1.78±1.40 0.060*†
       Rigidity 3.65±3.15 2.62±2.82 0.050*† 3.11±2.47 1.68±1.53 0.100† 4.22±3.72 3.61±3.52 0.835*†
       Bradykinesia 21.35±6.37 18.43±6.54 <0.001*† 20.42±6.46 16.68±7.01 0.010† 22.33±6.30 20.28±5.61 0.335*†
       Gait and balance 3.22±2.49 2.41±1.99 0.035† 3.11±2.33 2.26±2.02 0.110† 3.33±2.70 2.56±2.01 0.600†
       Tremor 5.22±3.97 4.24±4.25 0.360† 5.21±3.79 5.05±4.88 >0.999† 5.22±4.26 3.39±3.40 0.255†
      MDS-UPDRS Part 4 - - - - - - 5.83±2.62 3.39±3.11 0.001
       Dyskinesia - - - - - - 0.39±1.24 0.67±1.41 0.900*†
       Motor fluctuation - - - - - - 5.44±2.46 2.72±2.68 <0.001†
      Table 1. Comparison of motor symptoms at baseline and 8 weeks after safinamide add-on therapy

      Values are presented as mean±standard deviation.

      due to non-normal distribution, analyzed using the Wilcoxon signed-rank test;

      adjusted for multiple comparisons within each scale.

      MDS-UPDRS, Movement Disorders Society-Unified Parkinson’s Disease Rating Scale.

      Table 1.

      JMD : Journal of Movement Disorders bluesky InBug Facebook X
      Follow JMD
      © The Korean Movement Disorder Society.
      Close layer
      TOP