Fatma Nazlı DURMAZ ÇELİK, Müge KUZU, Özlem AYKAÇ, Serhat ÖZKAN

Parkinson Hastalığı’nda Dopamin Agonistlerinin Kesilmesi: Retrospektif Bir Analiz

Parkinson hastalığında dopamin agonisti (DA) tedavisindeki en önemli zorluk, etkisinden daha ağır basabilen ve hatta tedavinin kesilmesine yol açabilen yan etkileridir. DA'lar için kesilme oranlarının bire bir karşılaştıran çalışmlar ise çok sınırlıdır. Parkinson hastalığı (PH) olan hastalarda pramipeksol ve ropinirol tedavilerinin kesilme sıklığını ve özelliklerini araştırmayı ve bunların kesilmesine ilişkin risk faktörlerini belirlemeyi amaçladık. DA tedavisi (pramipeksol veya ropinirol) uygulanan 329 hastanın verileri geriye dönük olarak belirlendi. İki DA grubu arasında demografik özellikler, hastalık süresi, levodopa eşdeğer dozu, dopamin agonist dozu, ilgili yan etkiler, DA tedavi süresi ve Hoehn ve Yahr (HY) ölçek skorları karşılaştırıldı. Olumsuz etkilere bağlı olarak DA'lerin kesilme oranı% 51,6 idi. Psikiyatrik yan etkiler (%14,3) tedaviyi bırakmanın en sık nedeniyken, dürtü kontrol bozuklukları (DKB) ve pedal ödemi diğer öne çıkan nedenlerdi. Pramipeksol grubunda HY evre 2 ve 3 olan hastalarda tedaviyi bırakma oranı daha yüksekti, yine başlangıç yaşı ve hastalık süresi arttıkça bıraka oranı artmaktaydı . Ropinirol grubunda DKB daha yüksek prevalansa sahipti. Gündüz uykululuk, kabızlık ve baş ağrısı gibi sık görülen yan etkiler DA'lerin kesilmesinin nedeni olarak bulunmadı; daha ziyade psikoz, dürtü kontrol bozukluğu ve pedal ödemi nedeniyle hastalar bu tedavileri çoğunlukla bırakmıştı. Hastaların yarısından fazlasında yan etkilerin tedavinin kesilmesine yol açması dikkat çekicidir.

Anahtar Kelimeler:

Parkinson hastalığı, yan etki, dopamin agonisti, Parkinson's disease, side effects, dopamine agonists

Discontinuation of Dopamine Agonists in Parkinson’s Disease: A Retrospective Analysis

The most significant difficulty in dopamine agonist (DA) treatment is its adverse effects which may outweigh its efficacy or even be disabling leading to discontinuation. Limited data is available to provide a head-to-head comparison of the discontinuation rates for DAs. We aimed to investigate the prevalence and characteristics of the discontinuation of pramipexole and ropinirole treatments and to determine the risk factors related to their discontinuation in patients with Parkinson’s disease (PD). The data of 329 patients that underwent DA treatment (pramipexole or ropinirole) were retrospectively determined. Demographics, disease duration, levodopa equivalent dose, dopamine agonist dosage, related adverse effects, duration of DA treatment, and the Hoehn and Yahr (HY) scale scores were compared between the two DA groups. The rate of discontinuation of the DAs due to adverse effects was 51.6%. Psychiatric side effects (14.3%) were the most common reason for discontinuation, and impulse control disorders (ICD) and pedal edema were the other prominent reasons. The discontinuation rate was higher among the patients with HY stage 2 and 3 in the pramipexole group, increased age at onset, and increased disease duration. In the ropinirole group, ICD had higher prevalence. The odds ratio of the ICD risk was found to be 2.58 times higher in the ropinirole group. Common side effects such as daytime sleepiness, constipation, and headache were not found to be reasons for the discontinuation of DAs; rather, the patients mostly discontinued these treatments due to psychosis, impulse control disorder, and pedal edema. It is noteworthy that adverse effects led to the discontinuation of treatment in over half of the patients. Further prospective randomized controlled studies on the reasons for DA discontinuation and related risk factors will be beneficial.

Keywords:

Discontinuation, dopamine agonists, Parkinson’s disease, adverse effect,

PDF

___

1. Garcia-Ruiz PJ, Martinez Castrillo JC, Alonso-Canovas A, Herranz Barcenas A, Vela L, Sanchez Alonso P, et al. Impulse control disorder in patients with Parkinson's disease under dopamine agonist therapy: a multicentre study. J Neurol Neurosurg Psychiatry. 2014;85(8):840-4.
2. Ferreira JJ, Katzenschlager R, Bloem BR, Bonuccelli U, Burn D, Deuschl G, et al. Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease. Eur J Neurol. 2013;20(1):5-15. 3. Borovac JA. Side effects of a dopamine agonist therapy for Parkinson's disease: a mini-review of clinical pharmacology. Yale J Biol Med. 2016;89(1):37-47.
4. Alonso Canovas A, Luquin Piudo R, Garcia Ruiz-Espiga P, Burguera JA, Campos Arillo V, Castro A, et al. Dopaminergic agonists in Parkinson's disease. Neurologia. 2014;29(4):230-41.
5. Gibb WRG, Lees A. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s dise- ase. J Neurol Neurosurg Psychiatry. 1988;51:745-52.
6. Schapira AHV, Barone P, Hauser RA, Mizuno Y, Rascol O, Busse M, et al. Extended-release pramipexole in advanced Parkinson disease A randomized controlled trial. Neurology. 2011;77(8):767-74.
7. Poewe W, Rascol O, Barone P, Hauser RA, Mizuno Y, Haaksma M, et al. Extended-release pramipexole in early Parkinson disease A 33-week randomized controlled trial. Neurology. 2011;77(8):759-66.
8. Hauser RA, Schapira AHV, Barone P, Mizuno Y, Rascol O, Busse M, et al. Long-term safety and sustained efficacy of extended-release pramipexole in early and advanced Parkinson's disease. European Journal of Neurology. 2014;21(5):736-43. 9. Schapira AHV, McDermott MP, Barone P, Comella CL, Albrecht S, Hsu HH, et al. Pramipexole in patients with early Parkinson's disease (PROUD): a randomised delayed-start trial. Lancet Neurology. 2013;12(8):747-55.
10. Stocchi F, Giorgi L, Hunter B, Schapira AH. PREPARED: Comparison of prolonged and immediate release ropinirole in advanced Parkinson's disease. Mov Disord. 2011;26(7):1259-65.
11. Mizuno Y, Yamamoto M, Kuno S, Hasegawa K, Hattori N, Kagimura T, et al. Efficacy and safety of extended- versus immediate-release pramipexole in Japanese patients with advanced and L-dopa-undertreated Parkinson disease: a double-blind, randomized trial. Clin Neuropharmacol. 2012;35(4):174-81.
12. Chaudhuri KR, Todorova A, Nirenberg MJ, Parry M, Martin A, Martinez-Martin P, et al. A Pilot Prospective, Multicenter Observational Study of Dopamine Agonist Withdrawal Syndrome in Parkinson's Disease. Mov Disord Clin Pract. 2015;2(2):170-4.
13. Molina JA, Sainz-Artiga MJ, Fraile A, Jimenez-Jimenez FJ, Villanueva C, Orti-Pareja M, et al. Pathologic gambling in Parkinson's disease: a behavioral manifestation of pharmacologic treatment? Mov Disord. 2000;15(5):869-72.
14. Weintraub D, Siderowf AD, Potenza MN, Goveas J, Morales KH, Duda JE, et al. Association of dopamine agonist use with impulse control disorders in Parkinson disease. Arch Neurol. 2006;63(7):969-73.
15. Ambermoon P, Carter A, Hall WD, Dissanayaka NN, O'Sullivan JD. Impulse control disorders in patients with Parkinson's disease receiving dopamine replacement therapy: evidence and implications for the addictions field. Addiction. 2011;106(2):283-93.
16. Stocchi F, Radicati FG, Torti M. Drug safety evaluation of ropinirole prolonged release. Expert Opin Drug Saf. 2014;13(3):383-9.
17. Etminan M, Gill S, Samii A. Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson's disease: a meta-analysis. Drug Saf. 2003;26(6):439-44.
18. Pondal M, Marras C, Miyasaki J, Moro E, Armstrong MJ, Strafella AP, et al. Clinical features of dopamine agonist withdrawal syndrome in a movement disorders clinic. J Neurol Neurosurg Psychiatry. 2013;84(2):130-5.
19. Hollingworth SA, McGuire TM, Pache D, Eadie MJ. Dopamine Agonists: Time Pattern of Adverse Effects Reporting in Australia. Drugs Real World Outcomes. 2015;2(3):199-203.
20. Ceravolo R, Frosini D, Rossi C, Bonuccelli U. Impulse control disorders in Parkinson's disease: definition, epidemiology, risk factors, neurobiology and management. Parkinsonism Relat Disord. 2009;15 Suppl 4:S111-5.
21. Voon V, Sohr M, Lang AE, Potenza MN, Siderowf AD, Whetteckey J, et al. Impulse control disorders in Parkinson disease: a multicenter case--control study. Ann Neurol. 2011;69(6):986-96.
22. Grall-Bronnec M, Victorri-Vigneau C, Donnio Y, Leboucher J, Rousselet M, Thiabaud E, et al. Dopamine Agonists and Impulse Control Disorders: A Complex Association. Drug Saf. 2018;41(1):19-75.
23. Moore TJ, Glenmullen J, Mattison DR. Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs. JAMA Intern Med. 2014;174(12):1930-3.
24. Joutsa J, Martikainen K, Vahlberg T, Voon V, Kaasinen V. Impulse control disorders and depression in Finnish patients with Parkinson's disease. Parkinsonism Relat Disord. 2012;18(2):155-60.
25. Bharmal A, Lu C, Quickfall J, Crockford D, Suchowersky O. Outcomes of patients with Parkinson disease and pathological gambling. Can J Neurol Sci. 2010;37(4):473-7.
26. Tan EK, Ondo W. Clinical characteristics of pramipexole-induced peripheral edema. Arch Neurol-Chicago. 2000;57(5):729-32.