Combination therapy of levodopa with safinamide is more effective than with rasagiline and zonisamide in Asian Parkinson’s disease patients with motor fluctuations : a systematic review and network meta-analysis of randomized controlled trials
(2026) In Journal of Neurology 273(7).- Abstract
Background: Selegiline, rasagiline, safinamide, and zonisamide are commonly used with levodopa to manage motor fluctuations in Parkinson’s disease (PD). This study compared the efficacy and safety of these agents as adjuncts to levodopa in Asian PD patients with motor fluctuations. Methods: A Bayesian network meta-analysis (NMA) was conducted. Randomized controlled trials (RCTs) published from database inception to August 31, 2025 were identified through PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, and ClinicalTrials.gov. Eligible studies enrolled PD patients treated with levodopa plus any of the four agents. Primary outcomes included changes in daily OFF-time and Unified Parkinson’s Disease Rating Scale (UPDRS)... (More)
Background: Selegiline, rasagiline, safinamide, and zonisamide are commonly used with levodopa to manage motor fluctuations in Parkinson’s disease (PD). This study compared the efficacy and safety of these agents as adjuncts to levodopa in Asian PD patients with motor fluctuations. Methods: A Bayesian network meta-analysis (NMA) was conducted. Randomized controlled trials (RCTs) published from database inception to August 31, 2025 were identified through PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, and ClinicalTrials.gov. Eligible studies enrolled PD patients treated with levodopa plus any of the four agents. Primary outcomes included changes in daily OFF-time and Unified Parkinson’s Disease Rating Scale (UPDRS) Part III score. This study is registered in PROSPERO (CRD42024627701). Findings: Eleven RCTs involving 2824 patients were included, no eligible RCTs evaluating selegiline in Asian PD patients were identified for inclusion in the analysis. All combination therapies, except for zonisamide 25 mg, were more effective than levodopa plus placebo. NMA indicated that safinamide 100 mg was significantly superior to both rasagiline 1 mg and zonisamide 25 mg in reducing OFF-time (safinamide 100 mg vs. rasagiline 1 mg: MD = − 0·52, 95% CI − 0·97 to − 0·07; safinamide 100 mg vs. zonisamide 25 mg: MD = − 0·84, 95% CI − 1·46 to − 0·22) and improving UPDRS III score (safinamide 100 mg vs. rasagiline 1 mg: MD = − 2·00, 95% CI − 3·30 to − 0·67; safinamide 100 mg vs. zonisamide 25 mg: MD = − 2·50, 95% CI − 4·10 to − 0·94). Compared with zonisamide 50 mg, safinamide 100 mg showed a trend toward a reduction in OFF-time (MD = − 0·56, 95% CI − 1·18 to 0·08) and UPDRS III score (MD = − 1·40, 95% CI − 2·90 to 0·08). Safinamide 100 mg ranked first in SUCRA ranking for reducing OFF-time and UPDRS III score. These findings were robust in sensitivity analyses. Conclusions: The findings suggest that levodopa in combination with safinamide 100 mg is more efficacious than combinations with rasagiline 1 mg or zonisamide 25 mg for alleviating motor fluctuations and improving motor symptoms in Asian PD patients, and shows a more favourable (though not statistically significant) trend compared with zonisamide 50 mg.
(Less)
- author
- organization
- publishing date
- 2026-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Asian, Levodopa, Motor fluctuations, Parkinson’s disease, Safinamide
- in
- Journal of Neurology
- volume
- 273
- issue
- 7
- article number
- 396
- publisher
- Springer
- external identifiers
-
- pmid:42289483
- scopus:105041844270
- ISSN
- 0340-5354
- DOI
- 10.1007/s00415-026-13910-1
- language
- English
- LU publication?
- yes
- id
- 3468d8c0-684b-4fa7-8fd7-ffbb9d0c77bc
- date added to LUP
- 2026-09-02 13:46:14
- date last changed
- 2026-09-16 14:33:58
@article{3468d8c0-684b-4fa7-8fd7-ffbb9d0c77bc,
abstract = {{<p>Background: Selegiline, rasagiline, safinamide, and zonisamide are commonly used with levodopa to manage motor fluctuations in Parkinson’s disease (PD). This study compared the efficacy and safety of these agents as adjuncts to levodopa in Asian PD patients with motor fluctuations. Methods: A Bayesian network meta-analysis (NMA) was conducted. Randomized controlled trials (RCTs) published from database inception to August 31, 2025 were identified through PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, and ClinicalTrials.gov. Eligible studies enrolled PD patients treated with levodopa plus any of the four agents. Primary outcomes included changes in daily OFF-time and Unified Parkinson’s Disease Rating Scale (UPDRS) Part III score. This study is registered in PROSPERO (CRD42024627701). Findings: Eleven RCTs involving 2824 patients were included, no eligible RCTs evaluating selegiline in Asian PD patients were identified for inclusion in the analysis. All combination therapies, except for zonisamide 25 mg, were more effective than levodopa plus placebo. NMA indicated that safinamide 100 mg was significantly superior to both rasagiline 1 mg and zonisamide 25 mg in reducing OFF-time (safinamide 100 mg vs. rasagiline 1 mg: MD = − 0·52, 95% CI − 0·97 to − 0·07; safinamide 100 mg vs. zonisamide 25 mg: MD = − 0·84, 95% CI − 1·46 to − 0·22) and improving UPDRS III score (safinamide 100 mg vs. rasagiline 1 mg: MD = − 2·00, 95% CI − 3·30 to − 0·67; safinamide 100 mg vs. zonisamide 25 mg: MD = − 2·50, 95% CI − 4·10 to − 0·94). Compared with zonisamide 50 mg, safinamide 100 mg showed a trend toward a reduction in OFF-time (MD = − 0·56, 95% CI − 1·18 to 0·08) and UPDRS III score (MD = − 1·40, 95% CI − 2·90 to 0·08). Safinamide 100 mg ranked first in SUCRA ranking for reducing OFF-time and UPDRS III score. These findings were robust in sensitivity analyses. Conclusions: The findings suggest that levodopa in combination with safinamide 100 mg is more efficacious than combinations with rasagiline 1 mg or zonisamide 25 mg for alleviating motor fluctuations and improving motor symptoms in Asian PD patients, and shows a more favourable (though not statistically significant) trend compared with zonisamide 50 mg.</p>}},
author = {{Wang, Yu and Wang, Xi Xi and Yuan, Bing Ji and Li, Xuan and Zhang, Yu Lei and Yang, Xing Huang and Hou, Duan Lu and Peng, Si Jia and Li, Xin Jun and Feng, Ya and Zhou, Zhi Dong and Tan, Eng King and Wu, Yun Cheng}},
issn = {{0340-5354}},
keywords = {{Asian; Levodopa; Motor fluctuations; Parkinson’s disease; Safinamide}},
language = {{eng}},
number = {{7}},
publisher = {{Springer}},
series = {{Journal of Neurology}},
title = {{Combination therapy of levodopa with safinamide is more effective than with rasagiline and zonisamide in Asian Parkinson’s disease patients with motor fluctuations : a systematic review and network meta-analysis of randomized controlled trials}},
url = {{http://dx.doi.org/10.1007/s00415-026-13910-1}},
doi = {{10.1007/s00415-026-13910-1}},
volume = {{273}},
year = {{2026}},
}