Comparative Efficacy and Safety of Safinamide and Rasagiline in the Treatment of Parkinson’s Disease: A Meta-Analysis and Systematic Review

Year : 2024 | Volume : 14 | Issue : 03 | Page : 74 91
    By

    Joy Das,

  • Utpal Bhui,

  • Soumyadip Nayak,

  • Rahul Bishayee,

  • Udita Dutta,

  • Poulomi Mishra,

  • Radheshyam Pal,

  • Pratibha Bhowmick,

  • Mithun Bhowmick,

  1. Research scholar, Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
  2. Research scholar, Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, West Bengal, India
  3. Research scholar, Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
  4. Research scholar, Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
  5. Research scholar, Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kerala, India
  6. Assistant Professor, Department of Pharmacology, Pandaveswar School of Pharmacy, Pandaveswar, West Bengal, India
  7. Assistant Professor, Department of Pharmaceutical Sciences, Bengal College of Pharmaceutical Sciences & Research, Durgapur, West Bengal, India
  8. Professor, Department of Pharmaceutical Sciences, Bengal College of Pharmaceutical Sciences & Research, Durgapur, West Bengal, India
  9. Professor, Department of Pharmaceutical Sciences, Bengal College of Pharmaceutical Sciences & Research, Durgapur, West Bengal, India

Abstract

Background: Recent studies have suggested Rasagiline and Safinamide monotherapy as potential management options for Parkinson’s disease. Parkinson’s disease, a neurological disorder characterized by tremors and movement difficulties, necessitates treatments aimed at managing clinical symptoms. Levodopa remains the primary effective treatment for Parkinson’s disease symptoms; however, its long-term use often leads to motor complications in many patients. Additional therapeutic drugs, such as dopamine agonists and monoamine oxidase B inhibitors, including Safinamide and Rasagiline, have proven beneficial in enhancing levodopa therapy to better control motor symptoms. Studies have indicated that Safinamide significantly reduces motor fluctuations without exacerbating troublesome dyskinesia due to its dual mechanism. These offer distinct advantages for Parkinson’s disease patients with fluctuating symptoms compared to placebo or other medications. Transitioning from Rasagiline to Safinamide has been shown to improve the “ON-OFF” effect, where Parkinsonism symptoms worsen predictably as the effect of a levodopa dose fades. Safinamide might reduce the overall daily need for levodopa, enhance periods of improved symptoms (“ON” time), and potentially periods of worsened symptoms (‘OFF’ time), and potentially prove more effective than the other MAO-B inhibitors. This meta-analysis and systematic review aim to investigate the comparative efficacy and safety of Safinamide and Rasagiline among patients with motor complications as a viable and beneficial strategy to optimize antiparkinsonian medication. Objective: The objective of this study is to systematically evaluate and compare the clinical efficacy and safety profiles of Safinamide and Rasagiline as adjunct therapies for Parkinson’s disease among patients experiencing motor complications. Specifically, the study aims to investigate the effectiveness of Safinamide and Rasagiline in reducing motor fluctuations, improving overall motor symptoms, enhancing ‘ON’ time, reducing ‘OFF’ time, and potentially minimizing the need for levodopa dosage adjustments. Additionally, the study seeks to assess the safety profiles of both medications, including the incidence of adverse events and their impact on potential tolerability and quality of life. The evaluation will be conducted using standardized measures, such as the Unified Parkinson’s Disease Rating Scale Part III and the clinical global impression of severity (CGIS) score levels, providing objective assessments of motor symptoms severity and overall disease severity, respectively. Ultimately, the research aims to provide valuable insights into the optimal pharmacotherapeutics strategies for managing motor complications in Parkinson’s disease, thereby contributing to the optimization of antiparkinsonian medication regimen. Methodology: To identify relevant studies, we conducted a comprehensive computerized literature search covering Pubmed, Google Scholar, Embase, ScienceDirect, Scopus, and Embase up to 2023. We concentrated our efforts on randomized controlled trials that directly compared the efficacy and safety of Safinamide and Rasagiline against placebo groups. Our primary outcomes of interest include assessing alterations in UPDRS II, UPDRS III, and CGIS scores, alongside monitoring the incidence of adverse events. We employed mean difference (MD), standardized mean difference (SMD), and risk ratio (RR), and calculated 95% confidence intervals (CI) to quantify the effect sizes and their statistical significance. Additionally, to assess the degree of heterogeneity across studies, we utilized the I2 test. Results: Our analysis revealed significant improvements in the Safinamide group compared to the placebo group across various measures. Firstly, the MD of changes in “UPDRS II” favored the Safinamide group, with a value of 0.71 (95% CI ranging from –1.04 to –0.37). Moreover, examining changes in “UPDRS III”, we observed a similar trend. The overall MD of changes in UPDRS III favored the Safinamide group, with a value of –1.83 (95% CI ranging from –2.43 to –1.23). Similarly, when evaluating the changes in CGIS scores, the overall MD was –0.18 (95% CI = –0.24 to –0.12). On the other hand, a meta-analysis on Rasagiline concentrated on patients administered a daily dosage of 1 mg. Rasagiline exhibited significant improvements in “UPDRS II” and “UPDRS III” scores compared to the placebo group. However, notable heterogeneity among the studies was evident, with an I2 value exceeding 70%. Importantly, neither Safinamide nor Rasagiline showed an increased relative risk (RR) for any serious adverse events, or adverse events leading to withdrawal when compared to placebo. Upon concluding this analysis, it’s clear that Safinamide appears as a more favorable choice for patients with Parkinson’s disease when compared to Rasagiline. Conclusion: In conclusion, MAO-B inhibitors have proven to be valuable therapeutic options for managing PD. Rasagiline, for instance, has demonstrated its efficacy in reducing “off” time and increasing “on” time without any troublesome dyskinesia in PD patients experiencing fluctuations in symptoms. Moreover, clinical trials have underscored Rasagiline tolerability and low incidence of cognitive and behavioral AEs, solidifying its position as a valuable treatment choice for PD. On the other hand, Safinamide emerges as a compelling long-term adjunctive therapy alongside levodopa in PD patients.

Keywords: Parkinson’s disease, movement disorder, safinamide, rasagiline, UPDRS, CGIS, MAO-B inhibitors, dopamine agonist, motor fluctuations

[This article belongs to Research & Reviews: A Journal of Pharmacology ]

How to cite this article:
Joy Das, Utpal Bhui, Soumyadip Nayak, Rahul Bishayee, Udita Dutta, Poulomi Mishra, Radheshyam Pal, Pratibha Bhowmick, Mithun Bhowmick. Comparative Efficacy and Safety of Safinamide and Rasagiline in the Treatment of Parkinson’s Disease: A Meta-Analysis and Systematic Review. Research & Reviews: A Journal of Pharmacology. 2024; 14(03):74-91.
How to cite this URL:
Joy Das, Utpal Bhui, Soumyadip Nayak, Rahul Bishayee, Udita Dutta, Poulomi Mishra, Radheshyam Pal, Pratibha Bhowmick, Mithun Bhowmick. Comparative Efficacy and Safety of Safinamide and Rasagiline in the Treatment of Parkinson’s Disease: A Meta-Analysis and Systematic Review. Research & Reviews: A Journal of Pharmacology. 2024; 14(03):74-91. Available from: https://journals.stmjournals.com/rrjop/article=2024/view=191790


References

  1. Alborghetti, M., and Nicoletti, F. (2018). Different Generations of Type-B Monoamine Oxidase Inhibitors in Parkinson’s Disease: From Bench to Bedside. Curr. Neuropharmacol. 17: 861–873.
  2. Bandopadhyay, R., Mishra, N., Rana, R., Kaur, G., Ghoneim, M.M., Alshehri, S., et al. (2022). Molecular Mechanisms and Therapeutic Strategies for Levodopa-Induced Dyskinesia in Parkinson’s Disease: A Perspective Through Preclinical and Clinical Evidence. Pharmacol. 13: 1–23.
  3. Barone, P., Santangelo, G., Morgante, L., Onofrj, M., Meco, G., Abbruzzese, G., et al. (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: 1184–1191.
  4. Bhatia, S., and Gupta, A. (2003). Impairments in activities of daily living in Parkinson’s disease: Implications for management. 18: 209–214.
  5. Bianchini, E., Sforza, M., Rinaldi, D., Alborghetti, M., Carolis, L. De, Gatta, F. Della, et al. (2021). Switch from rasagiline to safinamide in fluctuating Parkinson’s disease patients: a retrospective, pilot study. Neurol. Res. 43: 950–954.
  6. Borgohain, R., Szasz, J., Stanzione, P., Meshram, C., Bhatt, M., Chirilineau, D., et al. (2014a). Randomized trial of safinamide add-on to levodopa in Parkinson’s disease with motor fluctuations. Mov. Disord. 29: 229–237.
  7. Borgohain, R., Szasz, J., Stanzione, P., Meshram, C., Bhatt, M.H., Chirilineau, D., et al. (2014b). Two-Year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson’s disease. Disord. 29: 1273–1280.
  8. Camerucci, E., Stang, C.D., Hajeb, M., Turcano, P., Mullan, A.F., Martin, P., et al. (2021). Early-Onset Parkinsonism and Early-Onset Parkinson’s Disease: A Population-Based Study (2010-2015). J. Parkinsons. Dis. 11: 1197–1207.
  9. Capriotti, T., and Terzakis, K. (2016). Parkinson Disease. Home Healthc. Now 34: 300–307.
  10. Carmichael, O., and Lockhart, S. (2012). Clinical and Pathological Features of Parkinson’s Disease. Brain Imaging Behav. Neurosci. 289–320.
  11. Chang, D., Nalls, M.A., Hallgrímsdóttir, I.B., Hunkapiller, J., Brug, M. van der, Cai, F., et al. (2017). A meta-analysis of genome-wide association studies identifies 17 new Parkinson’s disease risk loci. Nat. Genet. 49: 1511–1516.
  12. Csoti, I., Herbst, H., Urban, P., Woitalla, D., and Wüllner, U. (2019). Polypharmacy in Parkinson’s disease: risks and benefits with little evidence. J. Neural Transm. 126: 871–878.
  13. Dehay, B., and Fernagut, P.O. (2016). Alpha-synuclein-based models of Parkinson’s disease. Rev. Neurol. (Paris). 172: 371–378.
  14. deSouza, R.M., and Schapira, A. (2017). Safinamide for the treatment of Parkinson’s disease. Expert Opin. Pharmacother. 18: 937–943.
  15. Dezsi, L., and Vecsei, L. (2017). Monoamine Oxidase B Inhibitors in Parkinson’s Disease. CNS Neurol. Disord. – Drug Targets 16: 425–439.
  16. Diering, and Nishijima, Daniel; K. Simel, David L; Wisner, David H; Holmes, J.F. (2016). The usual suspects, dopamine and alpha synuclein, conspire to cause neurodegeneration. Physiol. Behav. 176: 139–148.
  17. Elbaz, A., Carcaillon, L., Kab, S., and Moisan, F. (2015). EPIDEMIOLOGY OF PARKINSON ’ S DISEASE The Rotterdam Study. Rev. Neurol. (Paris). 1580: 1–13.
  18. , S., G., A., M., O., H., K., A., S., A., T., et al. (2004). Improvement of motor function in early Parkinson disease by safinamide. Neurology 63: 746–748.
  19. Farrah, K., Young, K., Tunis, M.C., and Zhao, L. (2019). Risk of bias tools in systematic reviews of health interventions: an analysis of PROSPERO-registered protocols. Syst. Rev. 8: 1–9.
  20. Fereshtehnejad, S.M. (2016). Strategies to maintain quality of life among people with Parkinson’s disease: what works? Neurodegener. Dis. Manag. 6: 399–415.
  21. Hanagasi, H.A., Gurvit, H., Unsalan, P., Horozoglu, H., Tuncer, N., Feyzioglu, A., et al. (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: 1851–1858.
  22. Hansen, C., and Li, J.Y. (2012). Beyond α-synuclein transfer: Pathology propagation in Parkinson’s disease. Trends Mol. Med. 18: 248–255.
  23. Hattori, N., Takeda, A., Takeda, S., Nishimura, A., Kitagawa, T., Mochizuki, H., et al. (2019). Rasagiline monotherapy in early Parkinson’s disease: A phase 3, randomized study in Japan. Park. Relat. Disord. 60: 146–152.
  24. Hauser, R.A., Silver, D., Choudhry, A., Eyal, E., and Isaacson, S. (2014). Randomized, controlled trial of rasagiline as an add-on to dopamine agonists in Parkinson’s disease. Mov. Disord. 29: 1028–1034.
  25. Hou, J.G.G., and Lai, E.C. (2007). Non-motor symptoms of Parkinson’s disease. Int. J. Gerontol. 1: 53–64.
  26. Hwang, H., and Norris, S.A. (2021). Managing Advanced Parkinson Disease. J. Geriatr. Psychiatry Neurol. 34: 289–300.
  27. Kulisevsky, J., Martínez-Horta, S., Campolongo, A., Pascual-Sedano, B., Marín-Lahoz, J., Bejr-kasem, H., et al. (2022). A Randomized Clinical Trial to Evaluate the Effects of Safinamide on Apathetic Non-demented Patients With Parkinson’s Disease. Front. Neurol. 13:.
  28. Lee, A., and Gilbert, R.M. (2016). Epidemiology of Parkinson Disease. Clin. 34: 955–965.
  29. Liguori, C., Stefani, A., Ruffini, R., Mercuri, N.B., and Pierantozzi, M. (2018). Safinamide effect on sleep disturbances and daytime sleepiness in motor fluctuating Parkinson’s disease patients: A validated questionnaires-controlled study. Park. Relat. Disord. 57: 80–81.
  30. Lim, S.Y., Tan, A.H., Ahmad-Annuar, A., Klein, C., Tan, L.C.S., Rosales, R.L., et al. (2019). Parkinson’s disease in the Western Pacific Region. Lancet Neurol. 18: 865–879.
  31. Lücking, C.B., and Brice, A. (2000). Alpha-synuclein and Parkinson’s disease. Cell. Mol. Life Sci. 57: 1894–1908.
  32. Marras, C., Beck, J.C., Bower, J.H., Roberts, E., Ritz, B., Ross, G.W., et al. (2018). Prevalence of Parkinson’s disease across North America. Npj Park. Dis. 4: 1–7.
  33. Martí-Andrés, G., Jiménez-Bolaños, R., Arbelo-González, J.M., Pagonabarraga, J., Duran-Herrera, C., Valenti-Azcarate, R., et al. (2019). Safinamide in clinical practice: A Spanish multicenter cohort study. Brain Sci. 9: 1–11.
  34. Masood, N., and Jimenez-Shahed, J. (2023). Effective Management of “OFF” Episodes in Parkinson’s Disease: Emerging Treatment Strategies and Unmet Clinical Needs. Neuropsychiatr. Dis. Treat. 19: 247–266.
  35. Mehra, S., Sahay, S., and Maji, S.K. (2019). α-Synuclein misfolding and aggregation: Implications in Parkinson’s disease pathogenesis. Biochim. Biophys. Acta – Proteins Proteomics 1867: 890–908.
  36. Mínguez-Mínguez, S., Pozo, J.S.G. Del, and Jordán, J. (2013). Rasagiline in Parkinson’s disease: A review based on meta-analysis of clinical data. Res. 74: 78–86.
  37. Monaco, M.R. Lo, Petracca, M., Vetrano, D.L., Stasio, E. Di, Fusco, D., Ricciardi, D., et al. (2020). Safinamide as an adjunct therapy in older patients with Parkinson’s disease: a retrospective study. Aging Clin. Exp. Res. 32: 1369–1373.
  38. Morales-Casado MI, López-Ariztegui N, García-Meléndez DD, D.-M.A. (2022). Safinamide: Real life study. Efficacy in switch from rasagilina and low-dose treatment. Clin. Pharmacol. Adv. Appl. 37: S459–S459.
  39. Moustafa, A.A., Chakravarthy, S., Phillips, J.R., Gupta, A., Keri, S., Polner, B., et al. (2016). Motor symptoms in Parkinson’s disease: A unified framework. Neurosci. Biobehav. Rev. 68: 727–740.
  40. Müller, T. (2020). Safinamide in the treatment of Parkinson’s disease. Neurodegener. Dis. Manag. 10: 195–204.
  41. Ng, A.G.I. (2019). a Persistent Decline in the Age-Specific Fitness Components of an Organism Due To Internal Physiological Degeneration ” [2]. 11: 2–3.
  42. Nomoto, M., Ishida, T., Koebis, M., Kamei, T., Suzuki, I., Hattori, N., et al. (2022). Characteristics of wearing-off and motor symptoms improved by safinamide adjunct therapy in patients with Parkinson’s disease: A post hoc analysis of a Japanese phase 2/3 study. J. Neurol. Sci. 434: 120083.
  43. Oertel, W., and Schulz, J.B. (2016). Current and experimental treatments of Parkinson disease: A guide for neuroscientists. Neurochem. 139: 325–337.
  44. Olanow, C.W., Rascol, O., Hauser, R., Feigin, P.D., Jankovic, J., Lang, A., et al. (2009). A Double-Blind, Delayed-Start Trial of Rasagiline in Parkinson’s Disease. Engl. J. Med. 361: 1268–1278.
  45. Pacetti, D., Mezzetti, B., Balducci, F., Balzano, M., Carloni, P., Castiglioni, S., et al. (2020). Food quality and functionality.
  46. Pagonabarraga, J., Arbelo, J.M., Grandas, F., Luquin, M.R., Martín, P.M., Rodríguez-Oroz, M.C., et al. (2020). A Spanish consensus on the use of safinamide for parkinson’s disease in clinical practice. Brain Sci. 10:.
  47. Palareti, G., Legnani, C., Cosmi, B., Antonucci, E., Erba, N., Poli, D., et al. (2016). Comparison between different D-Dimer cutoff values to assess the individual risk of recurrent venous thromboembolism: Analysis of results obtained in the DULCIS study. Int. J. Lab. Hematol. 38: 42–49.
  48. Perez-Lloret, S., and Rascol, O. (2016). The safety and efficacy of safinamide mesylate for the treatment of Parkinsons disease. Expert Rev. Neurother. 16: 245–258.
  49. Poewe, W. (2008). Non-motor symptoms in Parkinson’s disease. Eur. J. Neurol. 15: 14–20.
  50. Politis, M., Wu, K., Molloy, S., Bain, P.G., Chaudhuri, K.R., and Piccini, P. (2010). Parkinson’s disease symptoms: The patient’s perspective. Mov. Disord. 25: 1646–1651.
  51. Prill, R., Karlsson, J., Ayeni, O.R., and Becker, R. (2021). Author guidelines for conducting systematic reviews and meta-analyses. Knee Surgery, Sport. Traumatol. Arthrosc. 29: 2739–2744.
  52. Qayyum, A. SYMPTOMS OF PARKINSON ’ S DISEASE.
  53. Rascol, O., Fitzer-Attas, C.J., Hauser, R., Jankovic, J., Lang, A., Langston, J.W., et al. (2011). A double-blind, delayed-start trial of rasagiline in Parkinson’s disease (the ADAGIO study): Prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes. Lancet Neurol. 10: 415–423.
  54. Reichmann, H., Schneider, C., and Löhle, M. (2009). Non-motor features of Parkinson’s disease: depression and dementia. Park. Relat. Disord. 15: 87–92.
  55. Robakis, D., and Fahn, S. (2015). Defining the Role of the Monoamine Oxidase-B Inhibitors for Parkinson’s Disease. CNS Drugs 29: 433–441.
  56. Ronconi, G., Calabria, S., Piccinni, C., Dondi, L., Pedrini, A., Esposito, I., et al. (2022). Prescription Pattern of Monoamine Oxidase B Inhibitors Combined with Levodopa: A Retrospective Observational Analysis of Italian Healthcare Administrative Databases. Drugs – Real World Outcomes 9: 391–401.
  57. Rus, T., Premzl, M., Križnar, N.Z., Kramberger, M.G., Rajnar, R., Ocepek, L., et al. (2022). Adverse effects of levodopa/carbidopa intrajejunal gel treatment: A single-center long-term follow-up study. Acta Neurol. Scand. 146: 537–544.
  58. Schapira, A.H.V., Fox, S.H., Hauser, R.A., Jankovic, J., Jost, W.H., Kenney, C., et al. (2017). 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. 74: 216–224.
  59. Schapira, A.H.V., Stocchi, F., Borgohain, R., Onofrj, M., Bhatt, M., Lorenzana, P., et al. (2013). Long-term efficacy and safety of safinamide as add-on therapy in early Parkinson’s disease. Eur. J. Neurol. 20: 271–280.
  60. Schrag, A., Hovris, A., Morley, D., Quinn, N., and Jahanshahi, M. (2003). Young- versus older-onset Parkinson’s disease: Impact of disease and psychosocial consequences. Mov. Disord. 18: 1250–1256.
  61. Sharaf, J., Williams, K.-A.D., Tariq, M., Acharekar, M. V, Guerrero Saldivia, S.E., Unnikrishnan, S., et al. (2022). The Efficacy of Safinamide in the Management of Parkinson’s Disease: A Systematic Review. Cureus 14:.
  62. Srinivasan, E., Chandrasekhar, G., Chandrasekar, P., Anbarasu, K., Vickram, A.S., Karunakaran, R., et al. (2021). Alpha-Synuclein Aggregation in Parkinson’s Disease. Front. Med. 8:.
  63. Stern, M.B., Marek, K.L., Friedman, J., Hauser, R.A., LeWitt, P.A., Tarsy, D., et al. (2004). Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson’s disease patients. Disord. 19: 916–923.
  64. Stocchi, F., Borgohain, R., Onofrj, M., Schapira, A.H.V., Bhatt, M., Lucini, V., et al. (2012). A randomized, double-blind, placebo-controlled trial of safinamide as add-on therapy in early Parkinson’s disease patients. Disord. 27: 106–112.
  65. Stocchi, F., Vacca, L., Grassini, P., Tomino, C., Caminiti, G., Casali, M., et al. (2021). Overnight switch from rasagiline to safinamide in Parkinson’s disease patients with motor fluctuations: a tolerability and safety study. Eur. J. Neurol. 28: 349–354.
  66. Tan, Y.Y., Jenner, P., and Chen, S. Di (2022). Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson’s Disease: Past, Present, and Future. J. Parkinsons. Dis. 12: 477–493.
  67. Tarolli, C.G., Zimmerman, G.A., Auinger, P., McIntosh, S., Horowitz, R.K., Kluger, B.M., et al. (2020). Symptom burden among individuals with Parkinson disease. Neurol. Clin. Pract. 10: 65–72.
  68. Volpicelli-Daley, L.A., Luk, K.C., Patel, T.P., Tanik, S.A., Riddle, D.M., Stieber, A., et al. (2011). Exogenous α-Synuclein Fibrils Induce Lewy Body Pathology Leading to Synaptic Dysfunction and Neuron Death. Neuron 72: 57–71.
  69. Wan, O.W., and Chung, K.K.K. (2012). The Role of Alpha-Synuclein Oligomerization and Aggregation in Cellular and Animal Models of Parkinson ’ s Disease. 7: 1–14.
  70. Xia, R., and Mao, Z.H. (2012). Progression of motor symptoms in Parkinson’s disease. Neurosci. Bull. 28: 39–48.
  71. Zhang, J., and Chew-Seng Tan, L. (2016). Revisiting the Medical Management of Parkinson’s Disease: Levodopa versus Dopamine Agonist. Curr. Neuropharmacol. 14: 356–363.
  72. Zhuo, C., Xue, R., Luo, L., Ji, F., Tian, H., Qu, H., et al. (2017a). Efficacy of antidepressive medication for depression in Parkinson disease: A network meta-analysis. Med. (United States) 96:.
  73. Zhuo, C., Zhu, X., Jiang, R., Ji, F., Su, Z., Xue, R., et al. (2017b). Comparison for Efficacy and Tolerability among Ten Drugs for Treatment of Parkinson’s Disease: A Network Meta-Analysis. Sci. Rep. 8: 1–14.
Regular Issue Subscription Review Article
Volume 14
Issue 03
Received 26/09/2024
Accepted 13/11/2024
Published 31/12/2024
675

Login


My IP

PlumX Metrics