Efficacy and Safety of MAO-B Inhibitors Safinamide and Zonisamide in Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Journal
CNS drugs
ISSN: 1179-1934
Titre abrégé: CNS Drugs
Pays: New Zealand
ID NLM: 9431220
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
accepted:
23
10
2023
medline:
24
11
2023
pubmed:
17
11
2023
entrez:
16
11
2023
Statut:
ppublish
Résumé
In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium channels and the subsequent release of glutamate. The aim of this systematic review and meta-analysis was to examine the efficacy and safety of both drugs compared with placebo on motor symptoms, cognitive function, and quality of life in patients with Parkinson's disease. We searched MEDLINE, EMBASE, Cochrane Central, Scopus, PsycINFO, and trials registries up to March 2023 for randomized controlled trials of adults with Parkinson's disease administered either safinamide or zonisamide and published in English. We excluded single-arm trials or if neither the efficacy nor safety outcomes of interest were reported. Primary outcomes were the change from baseline in Unified Parkinson's Disease Rating Scale section III (UPDRS-III) and serious adverse events. Secondary outcomes included a change from baseline in OFF-time, Parkinson's Disease Questionnaire 39 to evaluate quality of life, and Mini-Mental State Examination for cognitive function assessment. The meta-analysis was conducted using Review Manager 5.4.1. Random-effect models were used to calculate the pooled mean differences (MDs) and risk ratios with 95% confidence intervals (CIs). Subgroup analyses by medication, doses, Parkinson's disease stage, and risk of bias were conducted. We assessed the risk of bias using the Cochrane's risk of bias tool. Sensitivity analysis was conducted, and publication bias were evaluated. This meta-analysis was not externally funded, and the protocol is available on the Open Science Framework Registration ( https://doi.org/10.17605/OSF.IO/AMNP5 ). Of 3570 screened citations, 16 trials met inclusion criteria (4314 patients with Parkinson's disease). Ten safinamide trials were conducted in several countries. Six zonisamide trials were included, five of which were conducted in Japan and one in India. UPDRS Part III scores were significantly lower with both monoamine oxidase-B inhibitors than with placebo (MD = - 2.18; 95% CI - 2.88 to - 1.49; I Evidence suggests that novel monoamine oxidase-B inhibitors not only improve motor symptoms but also enhance patients' quality of life. The meta-analysis showed that both medications have a similar safety profile to placebo with regard to serious adverse events. The overall findings emphasize the effectiveness of safinamide and zonisamide in the treatment of Parkinson's disease as adjunct therapy. Further long-term studies examining the impact of these medications on motor and non-motor symptoms are necessary.
Sections du résumé
BACKGROUND AND OBJECTIVE
OBJECTIVE
In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium channels and the subsequent release of glutamate. The aim of this systematic review and meta-analysis was to examine the efficacy and safety of both drugs compared with placebo on motor symptoms, cognitive function, and quality of life in patients with Parkinson's disease.
METHODS
METHODS
We searched MEDLINE, EMBASE, Cochrane Central, Scopus, PsycINFO, and trials registries up to March 2023 for randomized controlled trials of adults with Parkinson's disease administered either safinamide or zonisamide and published in English. We excluded single-arm trials or if neither the efficacy nor safety outcomes of interest were reported. Primary outcomes were the change from baseline in Unified Parkinson's Disease Rating Scale section III (UPDRS-III) and serious adverse events. Secondary outcomes included a change from baseline in OFF-time, Parkinson's Disease Questionnaire 39 to evaluate quality of life, and Mini-Mental State Examination for cognitive function assessment. The meta-analysis was conducted using Review Manager 5.4.1. Random-effect models were used to calculate the pooled mean differences (MDs) and risk ratios with 95% confidence intervals (CIs). Subgroup analyses by medication, doses, Parkinson's disease stage, and risk of bias were conducted. We assessed the risk of bias using the Cochrane's risk of bias tool. Sensitivity analysis was conducted, and publication bias were evaluated. This meta-analysis was not externally funded, and the protocol is available on the Open Science Framework Registration ( https://doi.org/10.17605/OSF.IO/AMNP5 ).
RESULTS
RESULTS
Of 3570 screened citations, 16 trials met inclusion criteria (4314 patients with Parkinson's disease). Ten safinamide trials were conducted in several countries. Six zonisamide trials were included, five of which were conducted in Japan and one in India. UPDRS Part III scores were significantly lower with both monoamine oxidase-B inhibitors than with placebo (MD = - 2.18; 95% CI - 2.88 to - 1.49; I
CONCLUSIONS
CONCLUSIONS
Evidence suggests that novel monoamine oxidase-B inhibitors not only improve motor symptoms but also enhance patients' quality of life. The meta-analysis showed that both medications have a similar safety profile to placebo with regard to serious adverse events. The overall findings emphasize the effectiveness of safinamide and zonisamide in the treatment of Parkinson's disease as adjunct therapy. Further long-term studies examining the impact of these medications on motor and non-motor symptoms are necessary.
Identifiants
pubmed: 37973769
doi: 10.1007/s40263-023-01048-x
pii: 10.1007/s40263-023-01048-x
doi:
Substances chimiques
Zonisamide
459384H98V
safinamide
90ENL74SIG
Dopamine Agents
0
Monoamine Oxidase
EC 1.4.3.4
Types de publication
Meta-Analysis
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
941-956Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Références
Lonneke ML, de Lau MMB. The epidemiology of Parkinson’s disease. Lancet Neurol. 2006;5:525–35.
doi: 10.1016/S1474-4422(06)70471-9
Yan R, Cai H, Cui Y, et al. Zonisamide: in Parkinson’s disease. CNS Drugs. 2009;23:703–11.
doi: 10.2165/00023210-200923080-00007
Erkkinen MG, Kim MO, Geschwind MD. Clinical neurology and epidemiology of the major neurodegenerative diseases. Cold Spring Harb Perspect Biol. 2018. https://doi.org/10.1101/CSHPERSPECT.A033118 .
doi: 10.1101/CSHPERSPECT.A033118
pubmed: 28716886
pmcid: 5880171
Pringsheim T, Jette N, Frolkis A, Steeves TDL. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014;29:1583–90.
pubmed: 24976103
doi: 10.1002/mds.25945
Liu Y, Zhang Y, Zhu K, Chi S, Wang C, Xie A. Emerging role of sirtuin 2 in Parkinson’s Disease. Front Aging Neurosci. 2019. https://doi.org/10.3389/FNAGI.2019.00372 .
doi: 10.3389/FNAGI.2019.00372
pubmed: 32226373
pmcid: 6895020
Greenamyre JT, Hastings TG. Biomedicine. Parkinson’s: divergent causes, convergent mechanisms. Science. 2004;304:1120–2.
Wolters EC. Non-motor extranigral signs and symptoms in Parkinson’s disease. Park Relat Disord. 2009;15:S6-12.
doi: 10.1016/S1353-8020(09)70770-9
Boland DF, Stacy M. The economic and quality of life burden associated with Parkinson’s disease: a focus on symptoms. Am J Manag Care. 2012;18:168–75.
Poewe W, Antonini A, Zijlmans JC, Burkhard PR, Vingerhoets F. Levodopa in the treatment of Parkinson’s disease: an old drug still going strong. Clin Interv Aging. 2010;5:229–38.
pubmed: 20852670
pmcid: 2938030
Bastide MF, Meissner WG, Picconi B, et al. Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson’s disease. Prog Neurobiol. 2015;132:96–168.
pubmed: 26209473
doi: 10.1016/j.pneurobio.2015.07.002
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;33:1248–66.
pubmed: 29570866
doi: 10.1002/mds.27372
NICE. Overview: Parkinson’s disease in adults: guidance. https://www.nice.org.uk/guidance/NG71 . Accessed 27 Mar 2022.
Kong L, Xi J, Jiang Z, Yu X, Liu H, Wang Z. Zonisamide’s efficacy and safety on Parkinson’s Disease and dementia with lewy bodies: a meta-analysis and systematic review. Biomed Res Int. 2022;2022:4817488.
pubmed: 36132085
pmcid: 9484885
doi: 10.1155/2022/4817488
Sharaf J, Williams K-AD, Tariq M, et al. The efficacy of safinamide in the management of Parkinson’s Disease: a systematic review. Cureus. 2022;14:e29118.
pubmed: 36259026
pmcid: 9559607
Matsunaga S, Kishi T, Iwata N. Combination therapy with zonisamide and antiparkinson drugs for Parkinson’s disease: a meta-analysis. J Alzheimer’s Dis. 2017;56:1229–39.
doi: 10.3233/JAD-161068
Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ WV, editors. Cochrane handbook for systematic reviews of interventions version 6.3 (updated February 2022). 2022. www.training.cochrane.org/handbook . Accessed 27 Mar 2023.
Page MJ, McKenzie JE, Bossuyt PM, The PRISMA, et al. statement: an updated guideline for reporting systematic reviews. BMJ. 2020. https://doi.org/10.1136/BMJ.N71 .
doi: 10.1136/BMJ.N71
pubmed: 32933948
Higgins JPT, Savovi J, Page MJ, Elbers RG, SterneJAC. Chapter 8: Assessing risk of bias in a randomized trial. Available from: https://training.cochrane.org/handbook/current/chapter-08 . Accessed 27 Mar 2022.
Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.
pubmed: 12111919
doi: 10.1002/sim.1186
Ioannidis JPA, Trikalinos TA. The appropriateness of asymmetry tests for publication bias in meta-analyses: a large survey. CMAJ. 2007;176:1091–6.
pubmed: 17420491
pmcid: 1839799
doi: 10.1503/cmaj.060410
Murata M, Odawara T, Hasegawa K, Kajiwara R, Takeuchi H, Tagawa M, et al. Effect of zonisamide on parkinsonism in patients with dementia with Lewy bodies: a phase 3 randomized clinical trial. Park Relat Disord. 2020;76:91–7.
doi: 10.1016/j.parkreldis.2019.12.005
Murata M, Hasegawa K, Kanazawa I, et al. Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study. Neurology. 2007;68:45–50.
pubmed: 17200492
doi: 10.1212/01.wnl.0000250236.75053.16
Murata M, Hasegawa K, Kanazawa I, et al. Zonisamide improves wearing-off in Parkinson’s disease: a randomized, double-blind study. Mov Disord. 2015;30:1343–50.
pubmed: 26094993
doi: 10.1002/mds.26286
Murata M, Hasegawa K, Kanazawa I, et al. Randomized placebo-controlled trial of zonisamide in patients with Parkinson’s disease. Neurol Clin Neurosci. 2016;4:10–5.
doi: 10.1111/ncn3.12026
Murata M, Odawara T, Hasegawa K, Iiyama S, Nakamura M, Tagawa M, et al. Adjunct zonisamide to levodopa for DLB parkinsonism: a randomized double-blind phase 2 study. Neurology. 2018;90:e664–72.
pubmed: 29367449
pmcid: 5818167
doi: 10.1212/WNL.0000000000005010
Pillai K, Bhat P, Kumar A, Rajan R, Bhushan M, Vishnu, et al. Zonisamide add-on in tremor-dominant Parkinson’ s disease: a randomized controlled clinical trial. Park Relat Disord. 2022;105:1–6.
doi: 10.1016/j.parkreldis.2022.10.017
Stocchi F, Borgohain R, Onofrj M, Schapira AHV, Bhatt M, Lucini V, et al. A randomized, double-blind, placebo-controlled trial of safinamide as add-on therapy in early Parkinson’s disease patients. Mov Disord. 2012;27:106–12.
pubmed: 21913224
doi: 10.1002/mds.23954
Stocchi F, Arnold G, Onofrj M, et al. Improvement of motor function in early Parkinson disease by safinamide. Neurology. 2004;63:746–8.
pubmed: 15326260
doi: 10.1212/01.WNL.0000134672.44217.F7
Schapira AHV, Fox SH, Hauser RA, Jankovic J, Jost WH, Kenney C, et al. Assessment of safety and efficacy of safinamide as a levodopa adjunct in patients with Parkinson disease and motor fluctuations a randomized clinical trial. JAMA Neurol. 2017;74:216–24.
pubmed: 27942720
doi: 10.1001/jamaneurol.2016.4467
Hattori N, Tsuboi Y, Yamamoto A, Sasagawa Y, Nomoto M. Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson’s disease: a randomized, double-blind, placebo-controlled, phase II/III study. Park Relat Disord. 2020;75:17–23.
doi: 10.1016/j.parkreldis.2020.04.012
Borgohain R, Szasz J, Stanzione P, et al. Two-year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson’s disease. Mov Disord. 2014;29:1273–80.
pubmed: 25044402
doi: 10.1002/mds.25961
Schapira AHV, 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;20:271–80.
pubmed: 22967035
doi: 10.1111/j.1468-1331.2012.03840.x
Wei Q, Tan Y, Xu P, et al. The XINDI Study: a randomized phase III clinical trial evaluating the efficacy and safety of safinamide as add-on therapy to levodopa in Chinese patients with Parkinson’s disease with motor fluctuations. CNS Drugs. 2022;36:1217–27.
pubmed: 36346534
pmcid: 9641300
doi: 10.1007/s40263-022-00958-6
Kulisevsky J, Martinez-Horta S, Campolongo A, Pascual-Sedano B, Marin-Lahoz J, Bejr-kasem H, et al. A randomized clinical trial to evaluate the effects of safinamide on apathetic non-demented patients with Parkinson’s Disease. Front Neurol. 2022;13: 866502.
pubmed: 35720066
pmcid: 9201638
doi: 10.3389/fneur.2022.866502
Borgohain R, Szasz J, Stanzione P, et al. Randomized trial of safinamide add-on to levodopa in Parkinson’s disease with motor fluctuations. Mov Disord. 2014;29:229–37.
pubmed: 24323641
doi: 10.1002/mds.25751
ClinicalTrials.gov. Xadago report (2013): safinamide in early IPD , as add-on to dopamine agonist (MOTION). NCT00605683. Committee for Medicinal Products for Human Use (CHMP): p. 1–9
Müller T, Foley P. Clinical pharmacokinetics and pharmacodynamics of safinamide. Clin Pharmacokinet. 2017;56:251–61.
pubmed: 27665574
doi: 10.1007/s40262-016-0449-5
Cattaneo C, Kulisevsky J, Tubazio V, Castellani P. Long-term efficacy of safinamide on Parkinson’s Disease chronic pain. Adv Ther. 2018;35:515–22.
pubmed: 29542008
pmcid: 5910467
doi: 10.1007/s12325-018-0687-z
Cattaneo C, Jost WH, Bonizzoni E. Long-term efficacy of safinamide on symptoms severity and quality of life in fluctuating Parkinson’s disease patients. J Parkinsons Dis. 2020;10:89–97.
pubmed: 31594253
pmcid: 7029312
doi: 10.3233/JPD-191765
Cattaneo C, Müller T, Bonizzoni E, Lazzeri G, Kottakis I, Keywood C. Long-term effects of safinamide on mood fluctuations in Parkinson’s Disease. J Parkinsons Dis. 2017;7:629–34.
pubmed: 28777756
pmcid: 5676861
doi: 10.3233/JPD-171143
Odawara T, Hasegawa K, Kajiwara R, Takeuchi H, Tagawa M, Kosaka K, et al. Long-term efficacy and safety of zonisamide for treatment of parkinsonism in patients with dementia with lewy bodies: an open-label extension of a phase three randomized controlled trial. Am J Geriatr Psychiatry. 2022;30:314–28.
pubmed: 34420834
doi: 10.1016/j.jagp.2021.07.002
Martinez-Martin P, Rodriguez-Blazquez C, Forjaz MJ, Kurtis MM. Impact of pharmacotherapy on quality of life in patients with Parkinson’s disease. CNS Drugs. 2015;29:397–413.
pubmed: 25968563
doi: 10.1007/s40263-015-0247-x
Barone P, Santangelo G, Morgante L, et al. A randomized clinical trial to evaluate the effects of rasagiline on depressive symptoms in non-demented Parkinson’s disease patients. Eur J Neurol. 2015;22:1184–91.
pubmed: 25962410
pmcid: 4676931
doi: 10.1111/ene.12724
Li C, Xue L, Liu Y, Yang Z, Chi S, Xie A. Zonisamide for the treatment of Parkinson disease: a current update. Front Neurosci. 2020;14:1–12.
doi: 10.3389/fnins.2020.574652
Goel A, Sugumaran R, Narayan SK. Zonisamide in Parkinson’s disease: a current update. Neurol Sci. 2021;42:4123–9.
pubmed: 34448999
doi: 10.1007/s10072-021-05550-2
Miwa H. Zonisamide for the treatment of Parkinson’s disease. Expert Rev Neurother. 2007;7:1077–83.
pubmed: 17868006
doi: 10.1586/14737175.7.9.1077
Onofrj M, Bonanni L, Thomas A. An expert opinion on safinamide in Parkinson’s disease. Expert Opin Investig Drugs. 2008;17:1115–25.
pubmed: 18549347
doi: 10.1517/13543784.17.7.1115
Blair HA, Dhillon S. Safinamide: a review in Parkinson’s disease. CNS Drugs. 2017;31:169–76.
pubmed: 28110399
doi: 10.1007/s40263-017-0408-1
Yan R, Cai H, Cui Y. Comparative efficacy and safety of monoamine oxidase type B inhibitors plus channel blockers and monoamine oxidase type B inhibitors as adjuvant therapy to levodopa in the treatment of Parkinson’s disease: a network meta-analysis of randomized controlled. Eur J Neurol. 2023;30:1118–34.
pubmed: 36437702
doi: 10.1111/ene.15651
Giossi R, Carrara F, Mazzari M, et al. Overall efficacy and safety of safinamide in Parkinson’s disease: a systematic review and a meta-analysis. Clin Drug Investig. 2021;41:321–39.
pubmed: 33674954
pmcid: 8004480
doi: 10.1007/s40261-021-01011-y
Blesa R, Pujol M, Aguilar M, et al. Clinical validity of the “mini-mental state” for Spanish speaking communities. Neuropsychologia. 2001;39:1150–7.
pubmed: 11527552
doi: 10.1016/S0028-3932(01)00055-0
Tsai JC, Chen CW, Chu H, Yang HL, Chung MH, Liao YM, et al. Comparing the sensitivity, specificity, and predictive values of the Montreal Cognitive Assessment and Mini-Mental State Examination when screening people for mild cognitive impairment and dementia in Chinese population. Arch Psychiatr Nurs. 2016;30:486–91.
pubmed: 27455923
doi: 10.1016/j.apnu.2016.01.015
Fiorenzato E, Zurlo L, Cianci C, Garon M, Gandolfi T, Pistonesi F, et al. MoCA and MMSE subitems’ sensitivity across the PD-cognitive spectrum [abstract]. Mov Disord. 2023;37 (suppl 2).
Hagell P, Nygren C. The 39 item Parkinson’s disease questionnaire (PDQ-39) revisited: Implications for evidence based medicine. J Neurol Neurosurg Psychiatry. 2007;78:1191–8.
pubmed: 17442762
pmcid: 2117601
doi: 10.1136/jnnp.2006.111161
Stathis P, Papadopoulos G. Evaluation and validation of a patient-reported quality-of-life questionnaire for Parkinson’s disease. J Patient-Reported Outcomes. 2022. https://doi.org/10.1186/s41687-022-00427-0 .
doi: 10.1186/s41687-022-00427-0
Peto V, Jenkinson C, Fitzpatrick R. PDQ-39: a review of the development, validation and application of a Parkinson’s Disease quality of life questionnaire and its associated measures. J Neurol. 1998;245 Suppl.:10–4.
doi: 10.1007/PL00007730
Jenkinson C, Fitzpatrick R, Peto V, Greenhall R, Hyman N. The Parkinson’s disease questionnaire (PDQ-39): development and validation of a Parkinson’s disease summary index score. Age Ageing. 1997;26:353–7.
pubmed: 9351479
doi: 10.1093/ageing/26.5.353