Background: Parkinson’s disease (PD), which occurs in 1% of the population, is the second most common neurodegenerative disorder. Despite the broad spectrum of PD manifestations and high disease prevalence, there are insufficient data on medicine utilization and prescription strategies. The purpose of the current study was to analyze published data concerning treatment approaches and to compare them with Bulgarian therapeutic practice.
Design and methods: We conducted a systematic review of the PubMed and Google Scholar databases, and we calculated medicine utilization in Bulgaria during 2018 and 2019 using the WHO methodology.
Results: The literature search identified a total of 311 publications, but only 12 met the inclusion criteria. Eleven studies pointed out that levodopa-containing medicine are the most frequently used, followed by dopamine agonists. The highest rate was found for levodopa-containing products and decarboxylase inhibitor (1.06 and 1.33 DDD/1000 inh/day), followed by anticholinergic Biperiden (0.494 and 0.455 DDD/1000 inh/day) during 2018 and 2019 in Bulgaria.
Conclusion: Overall, the treatment approaches used in the last decade comply with guideline recommendations, despite variations in levodopa and dopamine agonist utilization. Even though new medicines have been approved for PD management, levodopa-containing products are still most often prescribed and used worldwide.
Parkinson’s Disease Collaborators. Global, regional, and national burden of Parkinson's disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2018;17:939-53. DOI: https://doi.org/10.1016/S1474-4422(18)30295-3
Khan AU, Akram M, Daniyal M, Zainab R. Awareness and current knowledge of Parkinson's disease: a neurodegenerative disorder. Int J Neurosci 2019;129:55-93. DOI: https://doi.org/10.1080/00207454.2018.1486837
Kalia LV, Lang AE. Parkinson's disease. Lancet 2015;386:896-912. DOI: https://doi.org/10.1016/S0140-6736(14)61393-3
Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain 2002;125:861-70. DOI: https://doi.org/10.1093/brain/awf080
Deumens R, Blokland A, Prickaerts J. Modeling Parkinson's disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 2002;175:303-17. DOI: https://doi.org/10.1006/exnr.2002.7891
Wishart S, Macphee GJ. Evaluation and management of the non-motor features of Parkinson's disease. Ther Adv Chronic Dis 2011;2:69-85. DOI: https://doi.org/10.1177/2040622310387847
Cacabelos R. Parkinson's Disease: From pathogenesis to pharmacogenomics. Int J Mol Sci 2017;18:551. DOI: https://doi.org/10.3390/ijms18030551
McFarthing K, Buff S, Rafaloff G, et al. Parkinson's Disease drug therapies in the clinical trial pipeline: 2020. J Parkinsons Dis 2020;10:757-74. DOI: https://doi.org/10.3233/JPD-202128
Mitkov J, Kondeva-Burdina M, Zlatkov A. Synthesis and preliminary hepatotoxicity evaluation of new caffeine-8-(2-thio)-propanoic hydrazid-hydrazone derivatives. Pharmacia 2019;66:99-106. DOI: https://doi.org/10.3897/pharmacia.66.e37263
Kondeva-Burdina M, Mitkov J, Georgieva M, et al. Cytotoxicity, brain antihypoxic activity and antioxidant properties of new derivatives of caffein-8-thioglycolic acid. Compt Rend Bulg Acad Sci 2016;69:521-8.
Jin H, Kanthasamy A, Ghosh A, et al. Mitochondria-targeted antioxidants for treatment of Parkinson's disease: preclinical and clinical outcomes. Biochim Biophys Acta 2014;842:1282-94. DOI: https://doi.org/10.1016/j.bbadis.2013.09.007
National Health Insurance Fund (NHIF). Information on the number of patients and reimbursement amount. Available from: https://www.nhif.bg/page/218
WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment 2018. Oslo; 2017.
WHO Collaborating Centre for Drug Statistics. ATC/DDD Index. Available from: https://www.whocc.no/atc_ddd_index/
National Statistical Institute. Population (Demography, Migration and Projections). Available from: https://www.nsi.bg/en/content/6593/population-demography-migration-and-projections
Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009;339:b2700. DOI: https://doi.org/10.1136/bmj.b2700
Kalilani L, Friesen D, Boudiaf N, Asgharnejad M. The characteristics and treatment patterns of patients with Parkinson’s disease in the United States and United Kingdom: A retrospective cohort study. PLoS One 2019:14:e0225723. DOI: https://doi.org/10.1371/journal.pone.0225723
Orayj K, Lane E. Patterns and determinants of prescribing for Parkinson's Disease: A systematic literature review. Parkinsons Dis 2019;2019:9237181. DOI: https://doi.org/10.1155/2019/9237181
Möller JC, Körner Y, Dodel RC, et al. Pharmacotherapy of Parkinson’s disease in Germany. J Neurol 2005:252:926–35. DOI: https://doi.org/10.1007/s00415-005-0784-1
Machado-Alba JE, Calvo-Torres LF, Gaviria-Mendoza A, Castrillón-Spitia JD. Prescribing patterns of antiparkinson drugs in a group of Colombian patients 2015. Biomedica 2018;38:417-26. DOI: https://doi.org/10.7705/biomedica.v38i4.3781
Shah J, Pranav J, Shikha S, Devang R, Supriya M. Drug utilization pattern and analysis of quality of life in Indian patients of Parkinson’s disease. Int J Basic Clin Pharmacol 2019;8:2092. DOI: https://doi.org/10.18203/2319-2003.ijbcp20194121
Nakaoka S, Ishizaki T, Urushihara H, et al. Prescribing pattern of anti-Parkinson drugs in Japan: A trend analysis from 2005 to 2010. PLoS One 2014;9:e99021. DOI: https://doi.org/10.1371/journal.pone.0099021
Kakariqi L, Sonila V. Ambulatory utilization of anti-parkinsonian drugs in Albania during 2004-2014. Int J Surg Med 2017;3:65-9. DOI: https://doi.org/10.26417/ejis.v3i2.p76-84
Kasamo S, Takeuchi M, Ikuno M, et al. Real-world pharmacological treatment patterns of patients with young-onset Parkinson's disease in Japan: a medical claims database analysis. J Neurol 2019;266:1944-52. DOI: https://doi.org/10.1007/s00415-019-09360-7
Gaida R, Truter I. Prescribing patterns for Parkinson’s disease in a South African patient population. J Appl Pharmaceut Sci 2014;4:29-34
Pitcher TL, Macaskill MR, Anderson TJ. Trends in antiparkinsonian medication use in new zealand: 1995-2011. Parkinsons Dis 2014;2014:379431. DOI: https://doi.org/10.1155/2014/379431
Crispo JA, Fortin Y, Thibault DP, et al. Trends in inpatient antiparkinson drug use in the USA, 2001-2012. Eur J Clin Pharmacol 2015;71:1011-9. DOI: https://doi.org/10.1007/s00228-015-1881-4
Hollingworth SA, Rush A, Hall WD, Eadie MJ. Utilization of anti-Parkinson drugs in Australia: 1995-2009. Pharmacoepidemiol Drug Saf 2011;20:450-6. DOI: https://doi.org/10.1002/pds.2114
Gruppo di lavoro OsMed. L’uso dei farmaci in Italia. Rapporto nazionale anno 2007. Roma: Il Pensiero Scientifico Editore; 2008.
National Agency for Medicines, Department of safety and drug information Finnish Statistics on Medicines. National Agency for Medicines; 2014.
Keus SH, Munneke M, Graziano M, et al. European Physiotherapy Guideline for Parkinson’s Disease KNGF/ParkinsonNet, Nijmegen. Available from: https:// www.parkinsonnet.nl/app/uploads/sites/3/2019/11/eu_guideline_parkinson_guideline_for_pt_s1.pdf
National Institute for Health and Care Excellence. Guideline No. 71 Parkinson's disease in adults: diagnosis and management,. 2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK447153/
Suzuki M, Arai M, Hayashi A, Ogino M. Adherence to treatment guideline recommendations for Parkinson's disease in Japan: A longitudinal analysis of a nationwide medical claims database between 2008 and 2016. PLoS One 2020;15:e0230213. DOI: https://doi.org/10.1371/journal.pone.0230213
Bulgarian algorithm for diagnostic and treatment of Parkinson’s disease. Official journal of the Association of movement disorders and multiple sclerosis and Bulgarian Association of clinical EMG and evoked potentials 2018;15.
Degli Esposti L, Piccinni C, Sangiorgi D, et al. Prescribing pattern and resource utilization of monoamine oxidase-B inhibitors in Parkinson treatment: comparison between rasagiline and selegiline. Neurol Sci 2016;37:227-34. DOI: https://doi.org/10.1007/s10072-015-2395-7
Iarkov A, Barreto GE, Grizzell JA, Echeverria V. Strategies for the treatment of Parkinson's Disease: Beyond dopamine. Front Aging Neurosci 2020;12:4. DOI: https://doi.org/10.3389/fnagi.2020.00004
Kasabova-Angelova A, Tzankova D, Mitkov J, et al. Xanthine derivatives as agents affecting non-dopaminergic neuroprotection in Parkinson`s disease. Curr Med Chem 2020;27:2021-36. DOI: https://doi.org/10.2174/0929867325666180821153316
Kasabova-Angelova A, Kondeva-Burdina M, Mitkov J, et al. Neuroprotective and MAOB inhibitory effects of a series of caffeine-8-thioglycolic acid amides. Braz J Pharmaceut Sci 2020;56:e18255. DOI: https://doi.org/10.1590/s2175-97902019000318255
Petzer JP, Petzer A. Caffeine as a lead compound for the design of therapeutic agents for the treatment of Parkinson's disease.Curr Med Chem 2015;22:975-88. DOI: https://doi.org/10.2174/0929867322666141215160015
Mitkov J, Kasabova-Angelova A, Kondeva-Burdina M, et al. Design, synthesis and evaluation of 8-thiosubstituted 1,3,7- trimethylxanthine hydrazones with in-vitro neuroprotective and MAO-B inhibitory activities. Med Chem 2020;16:326-39. DOI: https://doi.org/10.2174/1573406415666190531121927
Iorio-Morin C, Fomenko A, Kalia SK. Deep-brain stimulation for essential tremor and other tremor syndromes: A narrative review of current targets and clinical outcomes. Brain Sci 2020;10:925. DOI: https://doi.org/10.3390/brainsci10120925