Rasagiline combined with levodopa therapy versus levodopa monotherapy for patients with Parkinson’s disease: a systematic review
The aim of this report was to systematically evaluate the efficacy and safety of rasagiline (R) plus levodopa (l) (R + l) for the treatment of Parkinson’s disease (PD) compared with that of l monotherapy, in order to provide a reference resource for rational drug use.
Randomized controlled trials (RCTs) of R + l for PD published up to September 2018 were searched. Sensitivity analyses were also performed.
Fourteen RCTs with 2531 participants were included. Compared with l monotherapy, the pooled effects of R + l combination therapy on unified Parkinson’s disease rating scale (UPDRS) score were (SMD − 0.50, 95% CI − 0.70 to − 0.30, P < 0.00001) for UPDRS motor score, (SMD − 0.59, 95% CI − 0.79 to − 0.39, P < 0.00001) for UPDRS activities of daily living (ADL) score, (SMD − 0.65, 95% CI − 0.81 to − 0.49, P < 0.00001) for UPDRS total score. R + l combination therapy was better than l monotherapy in reducing daily off-time (SMD − 1.15, 95% CI − 2.13 to − 0.17, P = 0.02), but there was a statistically nonsignificant result in daily on-time increase (SMD 1.39, 95% CI − 0.69 to 3.48, P = 0.19). There were no statistical differences in number of adverse events (OR 1.33, 95% CI 0.97 to 1.82, P = 0.07) and number of dropout (OR 0.88, 95% CI 0.65 to 1.19, P = 0.39) between R + l combination therapy and l monotherapy.
R + l combination therapy was superior to l monotherapy for improvement of UPDRS scores and off-time in PD patients. Moreover, R + l combination therapy and l monotherapy were similar in terms of safety and tolerability.
KeywordsRasagiline Levodopa Parkinson’s disease Motor Off-time Systematic review
This study was supported by grants from the Natural Science Foundation of Guangxi Zhuang Autonomous Region of China (No. 2018GXNSFAA050002) and the Doctoral Scientific Research Foundation of Yulin Normal University of China (No. G20160006).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- 3.Cheung C, Bhimani R, Wyman JF, Konczak J, Zhang L, Mishra U, Terluk M, Kartha RV, Tuite P (2018) Effects of yoga on oxidative stress, motor function, and non-motor symptoms in Parkinson’s disease: a pilot randomized controlled trial. Pilot Feasibility Stud 4:162CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Barone P, Santangelo G, Morgante L, Onofrj M, Meco G, Abbruzzese G, Bonuccelli U, Cossu G, Pezzoli G, Stanzione P, Lopiano L, Antonini A, Tinazzi M (2015) A randomized clinical trial to evaluate the effects of rasagiline on depressive symptoms in non-demented Parkinson’s disease patients. Eur J Neurol 22(8):1184–1191CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Jiang DQ, Zhao SH, Li MX, Jiang LL, Wang Y, Wang Y (2018) Prostaglandin E1 plus methylcobalamin combination therapy versus prostaglandin E1 monotherapy for patients with diabetic peripheral neuropathy: a meta-analysis of randomized controlled trials. Medicine (Baltimore) 97(44):e13020CrossRefGoogle Scholar
- 24.Han Z (2016) Evaluate efficacy and safety of rasagiline mesylate tablets in treatment of idiopathic Parkinson’s disease in the basis of treatment of levodopa. Dissertation, Shanxi Medical UniversityGoogle Scholar
- 25.Hanagasi HA, Gurvit H, Unsalan P, Horozoglu H, Tuncer N, Feyzioglu A, Gunal DI, Yener GG, Cakmur R, Sahin HA, Emre M (2011) The effects of rasagiline on cognitive deficits in Parkinson’s disease patients without dementia: a randomized, double-blind, placebo-controlled, multicenter study. Mov Disord 26(10):1851–1858CrossRefPubMedGoogle Scholar
- 27.Li F, Chen M, Ma XT, Li XG, Tan H, He XY, Yuan P (2014) Efficacy and safety of rasagiline mesylate in treatment of idiopathic Parkinson’s disease with motor fluctuations: a randomized, double-blind, parallel-controlled, single-center trial. J Third Mil Med Univ 36(7):696–699Google Scholar
- 28.Liao PJ (2014) Clinical observation of efficacy of rasagiline mesylate combined with levodopa in the treatment of primary Parkinson’s disease with motor fluctuations. Prac J Card Cereb Pneumal Vasc Dis 22(9):78–79Google Scholar
- 30.Rabey JM, Sagi I, Huberman M, Melamed E, Korczyn A, Giladi N, Inzelberg R, Djaldetti R, Klein C, Berecz G (2000) Rasagiline mesylate, a new MAO-B inhibitor for the treatment of Parkinson’s disease: a double-blind study as adjunctive therapy to levodopa. Clin Neuropharmacol 23(6):324–330CrossRefPubMedGoogle Scholar
- 31.Rascol O, Brooks DJ, Melamed E, Oertel W, Poewe W, Stocchi F, Tolosa E (2005) Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, lasting effect in adjunct therapy with rasagiline given once daily, study): a randomised, double-blind, parallel-group trial. Lancet 365(9463):947–954CrossRefPubMedGoogle Scholar
- 33.Zhang L, Zhang Z, Chen Y, Qin X, Zhou H, Zhang C, Sun H, Tang R, Zheng J, Yi L, Deng L, Li J (2013) Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson’s disease: a randomized, double-blind, parallel-controlled, multi-centre trial. Int J Neuropsychopharmacol 16(7):1529–1537CrossRefPubMedGoogle Scholar
- 34.Zhang Z, Shao M, Chen S, Liu C, Peng R, Li Y, Wang J, Zhu S, Qu Q, Zhang X, Chen H, Sun X, Wang Y, Sun S, Zhang B, Li J, Pan X, Zhao G (2018) Adjunct rasagiline to treat Parkinson’s disease with motor fluctuations: a randomized, double-blind study in China. Transl Neurodegener 7:14CrossRefPubMedPubMedCentralGoogle Scholar
- 35.Kaludercic N, Carpi A, Nagayama T, Sivakumaran V, Zhu G, Lai EW, Bedja D, De Mario A, Chen K, Gabrielson KL, Lindsey ML, Pacak K, Takimoto E, Shih JC, Kass DA, Di Lisa F, Paolocci N (2014) Monoamine oxidase B prompts mitochondrial and cardiac dysfunction in pressure overloaded hearts. Antioxid Redox Signal 20(2):267–280CrossRefPubMedPubMedCentralGoogle Scholar
- 46.Elmer L, Schwid S, Eberly S, Goetz C, Fahn S, Kieburtz K, Oakes D, Blindauer K, Salzman P, Oren S, Prisco UL, Stern M, Shoulson I (2006) Rasagiline-associated motor improvement in PD occurs without worsening of cognitive and behavioral symptoms. J Neurol Sci 248(1–2):78–83CrossRefPubMedGoogle Scholar
- 47.Elbers RG, Verhoef J, van Wegen EE, Berendse HW, Kwakkel G (2015) Interventions for fatigue in Parkinson’s disease. Cochrane Database Syst Rev 10:CD010925Google Scholar