Skip to main content
SpringerLink
Log in

Rasagiline combined with levodopa therapy versus levodopa monotherapy for patients with Parkinson’s disease: a systematic review

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Objective

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.

Methods

Randomized controlled trials (RCTs) of R + l for PD published up to September 2018 were searched. Sensitivity analyses were also performed.

Results

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.

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Venkateshappa C, Harish G, Mythri RB, Mahadevan A, Bharath MM, Shankar SK (2012) Increased oxidative damage and decreased antioxidant function in aging human substantia nigra compared to striatum: implications for Parkinson’s disease. Neurochem Res 37(2):358–369

    Article  CAS  PubMed  Google Scholar 

  2. Ikeda K, Yoshikawa S, Kurokawa T, Yuzawa N, Nakao K, Mochizuki H (2009) TRK-820, a selective kappa opioid receptor agonist, could effectively ameliorate L-DOPA-induced dyskinesia symptoms in a rat model of Parkinson’s disease. Eur J Pharmacol 620(1–3):42–48

    Article  CAS  PubMed  Google Scholar 

  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 4:162

    Article  PubMed  PubMed Central  Google Scholar 

  4. Nagatsua T, Sawadab M (2009) L-dopa therapy for Parkinson’s disease: past, present, and future. Parkinsonism Relat Disord 15(Suppl 1):S3–S8

    Article  PubMed  Google Scholar 

  5. Marsili L, Marconi R, Colosimo C (2017) Treatment strategies in early Parkinson’s disease. Int Rev Neurobiol 132:345–360

    Article  PubMed  CAS  Google Scholar 

  6. Bendi VS, Shou J, Joy S, Torres-Russotto D (2018) Motor fluctuations and levodopa-induced dyskinesias in dopa-responsive dystonia. Parkinsonism Relat Disord 50:126–127

    Article  PubMed  Google Scholar 

  7. Szökő É, Tábi T, Riederer P, Vécsei L (2018) Pharmacological aspects of the neuroprotective effects of irreversible MAO-B inhibitors, selegiline and rasagiline, in Parkinson’s disease. J Neural Transm (Vienna) 125(11):1735–1749

    Article  CAS  Google Scholar 

  8. Robakis D, Fahn S (2015) Defining the role of the monoamine oxidase-B inhibitors for Parkinson’s disease. CNS Drugs 29(6):433–441

    Article  CAS  PubMed  Google Scholar 

  9. Youdim MB, Gross A, Finberg JP (2001) Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br J Pharmacol 132(2):500–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. McCormack PL (2014) Rasagiline: a review of its use in the treatment of idiopathic Parkinson’s disease. CNS Drugs 28(11):1083–1097

    Article  CAS  PubMed  Google Scholar 

  11. Youdim MB, Bar Am O, Yogev-Falach M, Weinreb O, Maruyama W, Naoi M, Amit T (2005) Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition. J Neurosci Res 79(1–2):172–179

    Article  CAS  PubMed  Google Scholar 

  12. Magyar K, Stocchi F, Fossati C, Torti M (2015) Rasagiline for the treatment of Parkinson’s disease: an update. Expert Opin Pharmacother 16(14):2231–2241

    Article  CAS  Google Scholar 

  13. Pistacchi M, Martinello F, Gioulis M, Zambito Marsala S (2014) Rasagiline and rapid symptomatic motor effect in Parkinson’s disease: review of literature. Neurol Ther 3(1):41–66

    Article  PubMed  Google Scholar 

  14. Weinreb O, Amit T, Sagi Y, Drigues N, Youdim MB (2009) Genomic and proteomic study to survey the mechanism of action of the anti-Parkinson’s disease drug, rasagiline compared with selegiline, in the rat midbrain. J Neural Transm (Vienna) 116(11):1457–1472

    Article  CAS  Google Scholar 

  15. Hattori N, Takeda A, Takeda S, Nishimura A, Kitagawa T, Mochizuki H, Nagai M, Takahashi R (2019) Rasagiline monotherapy in early Parkinson’s disease: a phase 3, randomized study in Japan. Parkinsonism Relat Disord 60:146–152

    Article  PubMed  Google 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):1184–1191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Frakey LL, Friedman JH (2017) Cognitive effects of rasagiline in mild-to-moderate stage Parkinson’s disease without dementia. J Neuropsychiatry Clin Neurosci 29(1):22–25

    Article  PubMed  Google Scholar 

  18. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097

    Article  PubMed  PubMed Central  Google Scholar 

  19. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17(1):1–12

    Article  CAS  PubMed  Google Scholar 

  20. Moher D, Pham B, Jones A, Cook DJ, Jadad AR, Moher M, Tugwell P, Klassen TP (1998) Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet 352(9128):609–613

    Article  CAS  PubMed  Google 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):e13020

    Article  CAS  Google Scholar 

  22. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  23. Parkinson Study Group (2005) A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol 62(2):241–248

    Article  Google 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 University

  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):1851–1858

    Article  PubMed  Google Scholar 

  26. Hauser RA, Stocchi F, Rascol O, Huyck SB, Capece R, Ho TW, Sklar P, Lines C, Michelson D, Hewitt D (2015) Preladenant as an adjunctive therapy with levodopa in Parkinson disease: two randomized clinical trials and lessons learned. JAMA Neurol 72(12):1491–1500

    Article  PubMed  Google 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):696–699

    Google 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):78–79

    Google Scholar 

  29. Lim TT, Kluger BM, Rodriguez RL, Malaty IA, Palacio R Jr, Ojo OO, Patel S, Gujrati Y, Nutter B, Swartz C, Hennessy C, Fernandez HH (2015) Rasagiline for the symptomatic treatment of fatigue in Parkinson’s disease. Mov Disord 30(13):1825–1830

    Article  CAS  PubMed  Google 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):324–330

    Article  CAS  PubMed  Google 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):947–954

    Article  CAS  PubMed  Google Scholar 

  32. Weintraub D, Hauser RA, Elm JJ, Pagan F, Davis MD, Choudhry A (2016) Rasagiline for mild cognitive impairment in Parkinson’s disease: a placebo-controlled trial. Mov Disord 31(5):709–714

    Article  CAS  PubMed  Google 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):1529–1537

    Article  CAS  PubMed  Google 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 7:14

    Article  PubMed  PubMed Central  CAS  Google 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):267–280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Dezsi L, Vecsei L (2017) Monoamine oxidase B inhibitors in Parkinson’s disease. CNS Neurol Disord Drug Targets 16(4):425–439

    Article  CAS  PubMed  Google Scholar 

  37. Mazumder MK, Paul R, Phukan BC, Dutta A, Chakrabarty J, Bhattacharya P, Borah A (2018) Garcinol, an effective monoamine oxidase-B inhibitor for the treatment of Parkinson’s disease. Med Hypotheses 117:54–58

    Article  CAS  PubMed  Google Scholar 

  38. Kong P, Zhang B, Lei P, Kong X, Zhang S, Li D, Zhang Y (2015) Neuroprotection of MAO-B inhibitor and dopamine agonist in Parkinson disease. Int J Clin Exp Med 8(1):431–439

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Hauser RA, Silver D, Choudhry A, Eyal E, Isaacson S (2014) Randomized, controlled trial of rasagiline as an add-on to dopamine agonists in Parkinson’s disease. Mov Disord 29(8):1028–1034

    Article  CAS  PubMed  Google Scholar 

  40. Cereda E, Cilia R, Canesi M, Tesei S, Mariani CB, Zecchinelli AL, Pezzoli G (2017) Efficacy of rasagiline and selegiline in Parkinson’s disease: a head-to-head 3-year retrospective case-control study. J Neurol 264(6):1254–1263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Chang Y, Wang LB, Li D, Lei K, Liu SY (2017) Efficacy of rasagiline for the treatment of Parkinson’s disease: an updated meta-analysis. Ann Med 49(5):421–434

    Article  CAS  PubMed  Google Scholar 

  42. Elmer LW (2013) Rasagiline adjunct therapy in patients with Parkinson’s disease: post hoc analyses of the PRESTO and LARGO trials. Parkinsonism Relat Disord 19(11):930–936

    Article  PubMed  Google Scholar 

  43. Stern MB, Marek KL, Friedman J, Hauser RA, LeWitt PA, Tarsy D, Olanow CW (2004) Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson’s disease patients. Mov Disord 19(8):916–923

    Article  PubMed  Google Scholar 

  44. Rinaldi D, Assogna F, Sforza M, Tagliente S, Pontieri FE (2018) Rasagiline for dysexecutive symptoms during wearing-off in Parkinson’s disease: a pilot study. Neurol Sci 39(1):141–143

    Article  PubMed  Google Scholar 

  45. Stocchi F, Rabey JM (2011) Effect of rasagiline as adjunct therapy to levodopa on severity of OFF in Parkinson’s disease. Eur J Neurol 18(12):1373–1378

    Article  CAS  PubMed  Google 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):78–83

    Article  CAS  PubMed  Google 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:CD010925

    Google Scholar 

  48. Perez-Lloret S, Rascol O (2011) Safety of rasagiline for the treatment of Parkinson’s disease. Expert Opin Drug Saf 10(4):633–643

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

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).

Author information

Authors and Affiliations

  1. Department of Biology and Pharmacy, Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology, Yulin Normal University, Jiaoyudong Road No. 1303, Yuzhou District, Yulin, 537000, Guangxi Zhuang Autonomous Region, China

    De-Qi Jiang, Hua-Kun Wang & Li-Lin Jiang

  2. Department of Pharmacy, Guangdong Province Hospital of Integrated Traditional Chinese and Western Medicine, Foshan, 528200, China

    Yan Wang

  3. Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China

    Ming-Xing Li

  4. Department of Pharmacy, Zhujiang Hospital of Southern Medical University, Guangzhou, 510282, China

    Yong Wang

Authors
  1. De-Qi Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hua-Kun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ming-Xing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li-Lin Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to De-Qi Jiang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOC 58 kb)

ESM 2

(DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, DQ., Wang, HK., Wang, Y. et al. Rasagiline combined with levodopa therapy versus levodopa monotherapy for patients with Parkinson’s disease: a systematic review. Neurol Sci 41, 101–109 (2020). https://doi.org/10.1007/s10072-019-04050-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-019-04050-8

Keywords

Search

Navigation