Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79:368–76.

Article  PubMed  CAS  Google Scholar 

Chaudhuri KR, Shapira AHV. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol. 2009;8(5):464–74.

Article  PubMed  CAS  Google Scholar 

Chase TN, Bibbiani F, Oh JD. Striatal glutamatergic mechanisms and extrapyramidal movement disorders. Neurotox Res. 2003;5:139–46.

Article  PubMed  Google Scholar 

Dorsey ER, Constantinescu R, Thompson JP, et al. Projected number of people with Parkinson’s disease in the most populous nations, 2005 through 2030. Neurology. 2007;68:384–6.

Article  PubMed  CAS  Google Scholar 

Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers. 2017;3:17013. https://doi.org/10.1038/nrdp.2017.13.

Article  PubMed  Google Scholar 

Rana AQ, Athar A, Owlia A, et al. Impact of ethnicity on non-motor symptoms of Parkinson’s disease. J Parkinsons Dis. 2012;2:281–5.

Article  PubMed  Google Scholar 

Li HJ, Zhang MF, Chen MX, et al. Validation of the nonmotor symptoms questionnaire for Parkinson’s disease: results from a Chinese pilot study. Int J Neurosci. 2015;125:929–35.

Article  PubMed  Google Scholar 

Jost WH. A critical appraisal of MAO-B inhibitors in the treatment of Parkinson’s disease. J Neural Transm. 2022;129:723–36.

Article  PubMed  CAS  Google Scholar 

Onofrj M, Bonanni L, Thomas A. An expert opinion on safinamide in Parkinson’s disease. Expert Opin Investig Drugs. 2007;17(7):1115–25.

Article  Google Scholar 

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(2):229–37.

Article  PubMed  CAS  Google Scholar 

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(10):1273–80.

Article  PubMed  CAS  Google Scholar 

Schapira AHV, Fox SH, Hauser RA, et al. Assessment of safety and efficacy of safinamide as a levodopa adjunct in patients with Parkinson’s disease and motor fluctuations: a randomized clinical trial. JAMA Neurol. 2017;74:216–24.

Article  PubMed  Google Scholar 

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. Parkinsonism Relat Disord. 2020;75:17–23.

Article  PubMed  Google Scholar 

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 Parkinson’s disease patients with motor fluctuations. CNS Drugs. 2022;36(11):1217–27.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Cattaneo C, Barone P, Bonizzoni E, Sardina M. Effects of safinamide on pain in fluctuating Parkinson’s disease patients: a post-hoc analysis. J Parkinsons Dis. 2017;7(1):95–101.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Cattaneo C, Müller T, Bonizzoni E, et al. Long-term effects of safinamide on mood fluctuations in Parkinson’s disease. J Parkinsons Dis. 2017;7(4):629–34.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Cattaneo C, Kulisevsky J, Tubazio V, Castellani P. Long-term efficacy of safinamide on Parkinson’s disease chronic pain. Adv Ther. 2018;35(4):515–22.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Pellecchia MT, Picillo M, Russillo MC, et al. Efficacy of safinamide and gender differences during routine clinical practice. Front Neurol. 2021;12:756304. https://doi.org/10.3389/fneur.2021.756304.

Article  PubMed  PubMed Central  Google Scholar 

Bhidayasiri R, Ishida T, Kamei T, et al. Safinamide as an adjunct to levodopa in Asian and Caucasian patients with Parkinson’s disease and motor fluctuations: a post-hoc analysis of the SETTLE study. J Mov Disord. 2023;16(2):180–90.

Article  PubMed  PubMed Central  Google Scholar 

Loprete L, Leuratti C, Cattaneo C, Thapar MM, Farrell C, Sardina M. Population pharmacokinetic and pharmacodynamic analyses of safinamide in subjects with Parkinson’s disease. Pharma Res Per. 2016;4(5):e00251. https://doi.org/10.1002/prp2.251.

Article  CAS  Google Scholar 

National Collaborating Centre for Chronic Conditions. Parkinson’s disease: national clinical guideline for diagnosis and management in primary and secondary care. London: Royal College of Physicians; 2006.

Google Scholar 

Hoehn M, Yahr M. Parkinsonism: onset, progression and mortality. Neurology. 1967;17(5):427–42.

Article  PubMed  CAS  Google Scholar 

Fahn S, Elton R, Members of the UPDRS Development Committee. The unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M, editors. Recent developments in Parkinson’s disease, vol. 2. Florham Park: McMellam Health Care Information; 1987. p. 153–63.

Google Scholar 

Peto V, Jenkinson C, Fitzpatrick R, Greenhall R. The development and validation of a short measure of functioning and well-being for individuals with Parkinson’s disease. Qual Lif Res. 1995;4:241–8.

Article  CAS  Google Scholar 

World Health Organization-Drug Dictionary (WHO-DD), Uppsala Monitoring Centre; 2020.

Medical Dictionary for Regulatory Activities (MedDRA) version 23.1, September 2020.

ICH Topic E10. Note for guidance on choice of control groups in clinical trials. CPMP/ICH/364/96 January 2001.

Ben-Joseph A, Marshall CR, Lees AJ, Noyce A. Ethnic variation in the manifestation of Parkinson’s disease: a narrative review. J Parkinsons Dis. 2020;10(1):31–45.

Article  PubMed  PubMed Central  Google Scholar 

Shulman LM, Gruber-Baldini AL, Anderson KE, et al. The clinically important difference on the unified Parkinson’s disease rating scale. Arch Neurol. 2010;67(1):64–70.

Article  PubMed  Google Scholar 

Blandini F, Porter RH, Greenamyre JT. Glutamate and Parkinson’s disease. Mol Neurobiol. 1996;12:73–94.

Article  PubMed  CAS  Google Scholar 

Pagonabarraga J, Tinazzi M, Caccia C, Jost WH. The role of glutamatergic neurotransmission in the motor and non-motor symptoms in Parkinson’s disease: clinical cases and a review of the literature. J Clin Neurosci. 2021;90:178–83.

Article  PubMed  CAS  Google Scholar 

Kulisevsky J, Martinez-Horta S, Campolongo A, 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. https://doi.org/10.3389/fneur.2022.86652.

Article  PubMed  PubMed Central  Google Scholar 

Cattaneo C, Sardina M, Bonizzoni E. Safinamide as add-on therapy to levodopa in mid- to late-stage Parkinson’s disease fluctuating patients: post-hoc analyses of studies 016 and SETTLE. J Parkinsons Dis. 2016;6(1):165–73.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson’s disease and motor fluctuations: the PRESTO study. Arch Neurol. 2005;62:241–8.

Article  Google Scholar 

Zhang Z, Shao M, Chen S, et al. Adjunct rasagiline to treat Parkinson’s disease with motor fluctuations; a randomized, double-blind study in China. Transl Neurodegener. 2018;7:14. https://doi.org/10.1186/s40035-018-0119-7.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ferreira JJ, Lees A, Rocha JF, et al. Opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations: a randomized, double-blind, controlled trial. Lancet Neurol. 2016;15(2):154–65.

Article  PubMed  CAS  Google Scholar 

Lees AJ, Ferreira J, Rascol O, et al. Opicapone as adjunct to levodopa therapy in patients with Parkinson’s disease and motor fluctuations: a randomized clinical trial. JAMA Neurol. 2017;74(2):197–206.

Article  PubMed  Google Scholar 

Cattaneo C, La Ferla R, Bonizzoni E, Sardina M. Long-term effects of safinamide on dyskinesia in mid- to late-stage Parkinson’s disease: a post-hoc analysis. J Parkinsons Dis. 2015;5(3):475–81.

Article  PubMed  PubMed Central  CAS  Google Scholar