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Clinical Review and Treatment of Select Adverse Effects of Dopamine Receptor Agonists in Parkinson’s Disease

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Abstract

Dopamine receptor agonists provide a viable alternative or adjunct to levodopa therapy in Parkinson’s disease and are associated with fewer motor complications and dyskinesia. However, all available dopamine agonists may cause profound adverse effects in some patients. In many cases, these adverse effects amplify non-motor symptoms that people with Parkinson’s disease may already be experiencing. Nausea from dopamine agonists generally lessens with time and may be responsive to both antiemetic therapy and complementary remedies, such as ginger, peppermint and chamomile. Unfortunately, compulsive behaviours, as well as peripheral oedema caused by dopamine agonists, are poorly responsive to pharmacological therapy and require a reduction or discontinuation of agonist therapy. Somnolence and associated sleep attacks generally require elimination of the agonist or the use of a stimulating agent. The necessity of treatment for hallucinations and psychosis associated with dopamine agonists must be thoroughly evaluated prior to initiating therapy. If a medication is initiated for hallucinations or psychosis, quetiapine or clozapine are agents of choice. Orthostatic hypotension, though not always symptomatic, responds well to nonpharmacological strategies and medications, including indometacin, midodrine and fludrocortisone. Care must be taken to educate patients with Parkinson’s disease about the common adverse effects of dopamine agonists and what can be done to lessen them.

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References

  1. Nussbaum RL, Ellis CE. Alzheimer’s disease and Parkinson’s disease. N Engl J Med 2003; 348: 1356–64

    Article  PubMed  CAS  Google Scholar 

  2. Factor SA, Weiner WJ, editors. Parkinson’s disease: diagnosis and clinical management. 2nd ed. New York: Demos, 2008

    Google Scholar 

  3. Fabbrini G, Brotchie JM, Grandas F, et al. Levodopa-induced dyskinesias. Mov Disord 2007; 22(10): 1379–89

    Article  PubMed  Google Scholar 

  4. Chen JJ, Swope DM. Pharmacotherapy for Parkinson’s disease. Pharmacotherapy 2007; 27: 161S–73S

    Article  PubMed  CAS  Google Scholar 

  5. Hubble JP. Long-term studies of dopamine agonists. Neurology 2002; 58Suppl. 1: S42–50

    Article  PubMed  CAS  Google Scholar 

  6. Reichmann H. Long-term treatment with dopamine agonists in idiopathic Parkinson’s disease. J Neurol 2000; 247Suppl. 4:IV/17–19

    Google Scholar 

  7. Parkinson Study Group CALM Cohort Investigators. Long-term effect of initiating pramipexole versus levodopa in early Parkinson disease. Arch Neurol 2009; 66(5): 563–70

    Article  Google Scholar 

  8. Hauser RA, Rascol O, Korczyn AD, et al. Ten-year follow-up of Parkinson’s disease patients randomized to initial therapy with ropinirole or levodopa. Mov Disord 2007; 22(16): 2409–17

    Article  PubMed  Google Scholar 

  9. Katzenschlager R, Head J, Schrag A, et al. Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD. Neurology 2008; 71: 474–80

    Article  PubMed  CAS  Google Scholar 

  10. Poewe W. Non-motor symptoms in Parkinson’s disease. Eur J Neurol 2008; 15Suppl. 1: 14–20

    Article  PubMed  Google Scholar 

  11. FDA. Public health advisory: pergolide (marketed as Permax). 2007 Mar 3 [online]. Available from URL: http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm051285.html [Accessed 2010 Jan 18]

  12. FDA. Neupro (rotigotine transdermal system). 2008 Apr 8 [online]. Available from URL: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094861.htm [Accessed 2010 Jan 18]

  13. Tan EK, Jankovic J. Choosing dopamine agonists in Parkinson’s disease. Clin Neuropharmacol 2001; 24(5): 247–53

    Article  PubMed  CAS  Google Scholar 

  14. Lebrun-Frenay C, Borg M. Choosing the right dopamine agonist for patients with Parkinson’s disease. Curr Med Res Opin 2002; 18(4): 209–14

    Article  PubMed  CAS  Google Scholar 

  15. Junghanns S, Glockler T, Reichmann H. Switching and combining of dopamine agonists. J Neurol 2004; 251Suppl. 6: VI/19–23

    CAS  Google Scholar 

  16. Obering CD, Chen JJ, Swope DM. Update on apomorphine for the rapid treatment of hypomobility (“off”) episodes in Parkinson’s disease. Pharmacotherapy 2006; 26(6): 840–52

    Article  PubMed  CAS  Google Scholar 

  17. Reichmann H, Herting B, Muller A, et al. Switching and combining dopamine agonists. J Neural Transm 2003; 110: 1393–400

    Article  PubMed  CAS  Google Scholar 

  18. Clinical Pharmacology [database]. Tampa (FL): Gold Standard, Inc., 2009 [online]. Available from URL: http://www.clinicalpharmacology.com [Accessed 2009 Oct 14]

  19. Parlodel® (bromocriptine mesylate tablets): US prescribing information. New York: Novartis, 2006

  20. Mirapex® (pramipexole dihydrochloride tablets): US prescribing information. Ridgefield (CT): Boehringer Ingelheim Pharmaceuticals, Inc., 2009

  21. Requip® (ropinirole tablets): US prescribing information. Research Triangle Park (NC): GlaxoSmithKline, 2009

  22. Neupro® (rotigotine transdermal system): US prescribing information. Mequon (WI): Schwarz Pharma, LLC, 2004

  23. Requip XL® (ropinirole extended release tablets): US prescribing information. Research Triangle Park (NC): GlaxoSmithKline, 2008

  24. Stewart D, Morgan E, Burn D, et al. Dopamine agonist switching in Parkinson’s disease. Hosp Med 2004; 65(4): 215–9

    PubMed  Google Scholar 

  25. Fahn S, Jankovic J, editors. Principles and practice of movement disorders. 2nd ed. Philadelphia (PA): Churchill Livingstone Elsevier, 2007

    Google Scholar 

  26. 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

    Article  PubMed  CAS  Google Scholar 

  27. Ernst E, Pittler MH. Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials. Br J Anaesth 2000; 84(3): 367–71

    Article  PubMed  CAS  Google Scholar 

  28. Antonini A, Cilia R. Behavioural adverse effects of dopaminergic treatments in Parkinson’s disease: incidence, neurobiological basis, management and prevention. Drug Saf 2009; 32(6):475–88

    Article  PubMed  CAS  Google Scholar 

  29. Voon V, Potenza MN, Thomsen T. Medication-related impulse control and repetitive behaviors in Parkinson’s disease. Curr Opin Neurol 2007; 20: 484–92

    Article  PubMed  Google Scholar 

  30. Friedman JH, Factor SA. Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson’s disease. Mov Disord 2000; 15(2): 201–11

    Article  PubMed  CAS  Google Scholar 

  31. Kujawa K, Leurgans S, Raman R, et al. Acute orthostatic hypotension when starting dopamine agonists in Parkinson’s disease. Arch Neurol 2000; 57: 1461–3

    Article  PubMed  CAS  Google Scholar 

  32. Pathak A, Senard JM. Pharmacology of orthostatic hypotension in Parkinson’s disease: from pathophysiology to management. Expert Rev Cardiovasc Ther 2004; 2(3): 393–403

    Article  PubMed  CAS  Google Scholar 

  33. Schoffer KL, Henderson RD, O’Maley K, et al. Non-pharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson’s disease. Mov Disord 2007; 22(11): 1543–9

    Article  PubMed  Google Scholar 

  34. Apokyn® (apomorphine hydrochloride injection): US prescribing information. Brisbane (CA): Tercica, Inc., 2009

  35. Ahmad N, Keith-Ferris J, Gooden E, et al. Making a case for domperidone in the treatment of gastrointestinal motility disorders. Curr Opin Pharmacol 2006; 6: 571–6

    Article  PubMed  CAS  Google Scholar 

  36. Reddymasu SC, Soykan I, McCallum RW. Domperidone: review of pharmacology and clinical applications in gastroenterology. Am J Gastroenterol 2007; 102: 2036–45

    Article  PubMed  CAS  Google Scholar 

  37. Barone JA. Domperidone: a peripherally acting dopamine2-receptor antagonist. Ann Pharmacother 1999; 33: 429–40

    Article  PubMed  CAS  Google Scholar 

  38. Champion MC, Hartnett M, Yen M. Domperidone, a new dopamine antagonist. CMAJ 1986; 135: 457–61

    PubMed  CAS  Google Scholar 

  39. Soykan I, Sarosiek I, Shifflett J, et al. Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with Parkinson’s disease. Mov Disord 1997; 12(6): 952–7

    Article  PubMed  CAS  Google Scholar 

  40. Natural Medicines Comprehensive Database. Stockton (CA): Therapeutic Research Faculty; 1995-2009 [online]. Available from URL: http://www.naturaldatabase.com/(S(0db2djzcs0kgz045ma21zqva))/home.aspx?cs=&s=ND [Accessed 2009 Oct 15]

  41. Berardi RR, editor. Handbook of nonprescription drugs: an interactive approach to self care. 15th ed. Washington, DC: American Pharmaceutical Association, 2006

    Google Scholar 

  42. Spirling LI, Daniels IR. Peppermint: more than just an after-dinner mint. J R Soc Promot Health 2001; 121(1): 62–3

    Article  PubMed  CAS  Google Scholar 

  43. Arnulf I. Excessive daytime sleepiness in parkinsonism. Sleep Med Rev 2005; 9: 185–200

    Article  PubMed  Google Scholar 

  44. Kumar R. Approved and investigational uses of modafinil: an evidence-based review. Drugs 2008; 68(13): 1803–39

    Article  PubMed  CAS  Google Scholar 

  45. Factor SA, Friedman JH, Lannon MC, et al. Clozapine for the treatment of drug-induced psychosis in Parkinson’s disease: results of the 12 week open label extension in the PSYCLOPS trial. Mov Disord 2001; 16(1): 135–9

    Article  PubMed  CAS  Google Scholar 

  46. Miyasaki JM, Shannon K, Voon V, et al. Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 66: 996–1002

    Article  PubMed  CAS  Google Scholar 

  47. Chou KL. Adverse events from the treatment of Parkinson’s disease. Neurol Clin 2008; 26: S65–83

    Article  PubMed  Google Scholar 

  48. Parkes JD. Domperidone and Parkinson’s disease. Clin Neuropharmacol 1986; 9(6): 517–32

    Article  PubMed  CAS  Google Scholar 

  49. Jost W. Gastrointestinal motility problems in patients with Parkinson’s disease: effects of antiparkinsonian treatment and guidelines for management. Drugs Aging 1997; 10(4): 249–58

    Article  PubMed  CAS  Google Scholar 

  50. Braun M, Cawello W, Boekens H, et al. Influence of domperidone on pharmacokinetics, safety and tolerability of the dopamine agonist rotigotine. Br J Clin Pharmacol 2008; 67(2): 209–15

    Article  PubMed  Google Scholar 

  51. FDA. FDA talk paper: FDA warns against women using unapproved drug, domperidone, to increase milk production. 2004 Jun 7 [online]. Available from URL: http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm073070.htm [Accessed 2010 Jan 18]

  52. Paus S, Brecht HM, Koster J, et al. Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson’s disease. Mov Disord 2003; 18(6): 659–67

    Article  PubMed  Google Scholar 

  53. Chaudhuri KR, Pal S, Brefel-Courbon C. ‘Sleep attacks’ or ‘unintended sleep episodes’ occur with dopamine agonists: is this a class effect? Drug Saf 2002; 25(7): 473–83

    Article  PubMed  CAS  Google Scholar 

  54. Brodsky MA, Godbold J, Roth T, et al. Sleepiness in Parkinson’s disease: a controlled study. Mov Disord 2003; 18(6): 668–72

    Article  PubMed  Google Scholar 

  55. Hobson DE, Lang AE, Martin WR, et al. Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian Movement Disorders Group. JAMA 2002; 287: 455–63

    Article  PubMed  Google Scholar 

  56. Hogl B, Seppi K, Brandauer E. Increased daytime sleepiness in Parkinson’s disease: a questionnaire survey. Mov Disord 2003; 18(3): 319–23

    Article  PubMed  Google Scholar 

  57. Razmy A, Lang AE, Shapiro CM. Predictors of impaired daytime sleep and wakefulness in patients with Parkinson disease treated with older (ergot) versus newer (nonergot) dopamine agonists. Arch Neurol 2004; 61: 97–102

    Article  PubMed  Google Scholar 

  58. Roth T, Schwartz JRL, Hirshkowitz M, et al. Evaluation of the safety of modafinil for treatment of excessive sleepiness. J Clin Sleep Med 2007; 3(6): 595–602

    PubMed  Google Scholar 

  59. Valentino RM, Foldvary-Schaefer N. Modafinil in the treatment of excessive daytime sleepiness. Cleve Clin J Med 2007; 74(8): 561–71

    Article  PubMed  Google Scholar 

  60. Ondo WG, Fayle R, Atassi F, et al. Modafinil for daytime somnolence in Parkinson’s disease: double blind, placebo controlled parallel trial. J Neurol Neurosurg Psychiatry 2005; 76: 1636–9

    Article  PubMed  CAS  Google Scholar 

  61. McKeon A, Josephs KA, Klos KJ, et al. Unusual compulsive behaviors primarily related to dopamine agonist therapy in Parkinson’s disease and multiple system atrophy. Parkinsonism Relat Disord 2007; 13: 516–9

    Article  PubMed  Google Scholar 

  62. Driver-Dunckley ED, Boble BN, Hentz JG, et al. Gambling and increased sexual desire with dopaminergic medications in restless legs syndrome. Clin Neuropharmacol 2007; 30(5): 249–55

    Article  PubMed  CAS  Google Scholar 

  63. Bostwick JM, Hecksel KA, Stevens SR, et al. Frequency of new-onset pathologic compulsive gambling or hypersexuality after drug treatment of idiopathic Parkinson disease. Mayo Clin Proc 2009; 84(4): 310–6

    PubMed  CAS  Google Scholar 

  64. Weintraub D, Koester J, Potenza M, et al. Dopaminergic therapy and impulse control disorders in Parkinson’s disease: top line results of a cross-sectional study of over 3000 patients [abstract]. Mov Disord 2008; 23Suppl. 4:38

    Google Scholar 

  65. Weintraub D. Dopamine and impulse control disorders in Parkinson’s disease. Ann Neurol 2008; 64 Suppl.: S93–100

    Article  PubMed  Google Scholar 

  66. Mamikonyan E, Siderowf AD, Duda JE, et al. Long-term follow-up of impulse control disorders in Parkinson’s disease. Mov Disord 2007; 23(1): 75–80

    Article  Google Scholar 

  67. Grosset D. Dopamine agonists and therapy compliance. Neurol Sci 2008; 29: S375–6

    Article  PubMed  Google Scholar 

  68. Kimber TE, Thompson PD, Kiley MA. Resolution of dopamine dysregulation syndrome following cessation of dopamine agonist therapy in Parkinson’s disease. J Clin Neurosci 2008; 15: 205–8

    Article  PubMed  CAS  Google Scholar 

  69. Nirenberg MJ, Waters C. Compulsive eating and weight gain related to dopamine agonist use. Mov Disord 2006; 21(4): 524–9

    Article  PubMed  Google Scholar 

  70. Rabinak CA, Nirenberg MJ. Dopamine agonist withdrawal syndrome in Parkinson disease. Arch Neurol 2010; 67(1): 58–63

    Article  PubMed  Google Scholar 

  71. Barnes J, David AS. Visual hallucinations in Parkinson’s disease: a review and phenomenological survey. J Neurol Neurosurg Psychiatry 2001; 70: 727–33

    Article  PubMed  CAS  Google Scholar 

  72. Fenelon G, Mahieux F, Huon R, et al. Hallucinations in Parkinson’s disease: prevalence, phenomenology and risk factors. Brain 2000; 123: 733–45

    Article  PubMed  Google Scholar 

  73. Ecker D, Unrath A, Kasubek J, et al. Dopamine agonists and their risk to induce psychotic episodes in Parkinson’s disease: a case-control study. BMC Neurol 2009; 9: 23–8

    Article  PubMed  Google Scholar 

  74. Biglan KM, Holloway RG, McDermott MP, et al. Risk factors for somnolence, edema, and hallucinations in early Parkinson’s disease. Neurology 2007; 69: 187–95

    Article  PubMed  Google Scholar 

  75. Reddy S, Factor SA, Molho ES, et al. The effect of quetiapine on psychosis and motor function in Parkinsonian patients with and without dementia. Mov Disord 2002; 17(4): 676–81

    Article  PubMed  Google Scholar 

  76. Fernandez HH, Trieschmann ME, Burke MA, et al. Long-term outcome of quetiapine use for psychosis among Parkinsonian patients. Mov Disord 2003; 18(5): 510–4

    Article  PubMed  Google Scholar 

  77. Papapetropoulos S, Argyriou AA, Ellul J. Factors associated with drug-induced visual hallucinations in Parkinson’s disease. J Neurol 2005; 252: 1223–8

    Article  PubMed  Google Scholar 

  78. Fernandez HH, Friedman JH, Jacques C, et al. Quetiapine for the treatment of drug-induced psychosis in Parkinson’s disease. Mov Disord 1999; 14(3): 484–7

    Article  PubMed  CAS  Google Scholar 

  79. Ondo WG, Tintner R, Dat Voung K, et al. Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson’s disease. Mov Disord 2005; 20(8): 958–63

    Article  PubMed  Google Scholar 

  80. Merims D, Balas M, Peretz C, et al. Rater-blinded, prospective comparison: quetiapine versus clozapine for Parkinson’s disease psychosis. Clin Neuropharmacol 2006; 29(6): 331–7

    Article  PubMed  CAS  Google Scholar 

  81. Rabey JM, Prokhorov T, Miniovitz A, et al. Effect of quetiapine in psychotic Parkinson’s disease patients: a double-blind labeled study of 3 months duration. Mov Disord 2007; 22(3): 313–8

    Article  PubMed  Google Scholar 

  82. Shotbolt P, Samuel M, Fox C, et al. A randomized controlled trial of quetiapine for psychosis in Parkinson’s disease. Neuropsychiatr Dis Treat 2009; 5: 327–32

    Article  PubMed  CAS  Google Scholar 

  83. The French Clozapine Parkinson Study Group. Clozapine in drug-induced psychosis in Parkinson’s disease. Lancet 1999; 353: 2041–2

    Article  Google Scholar 

  84. Senard JM, Rai S, Lapeyre-Mestre M. Prevalence of orthostatic hypotension in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997; 63: 584–9

    Article  PubMed  CAS  Google Scholar 

  85. Senard JM, Brefel-Courbon C, Rascol O, et al. Orthostatic hypotension in patients with Parkinson’s disease: pathophysiology and management. Drugs Aging 2001; 18(7): 495–505

    Article  PubMed  CAS  Google Scholar 

  86. Goldstein DS, Pechnik S, Holmes C, et al. Association between supine hypertension and orthostatic hypotension in autonomic failure. Hypertension 2003; 42: 136–42

    Article  PubMed  CAS  Google Scholar 

  87. Lang AE. Acute orthostatic hypotension when starting dopamine agonist therapy in Parkinson disease: the role of domperidone therapy [letter]. Arch Neurol 2001; 58: 835

    Article  PubMed  CAS  Google Scholar 

  88. Abate G, Polimeni RM, Cuccurullo F, et al. Effects of indomethacin on postural hypotension in Parkinsonism. BMJ 1979; 2: 1466–8

    Article  PubMed  CAS  Google Scholar 

  89. Hoehn MM. Levodopa-induced postural hypotension: treatment with fludrocortisone. Arch Neurol 1975; 32: 50–1

    Article  PubMed  CAS  Google Scholar 

  90. Low PA, Gilden JL, Freeman R, et al. Efficacy of midodrine versus placebo in neurogenic orthostatic hypotension: a randomized, double-blind multicenter study. JAMA 1997; 277: 1046–51

    Article  PubMed  CAS  Google Scholar 

  91. Jankovic J, Gilden JL, Hiner BC, et al. Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine. Am J Med 1993; 95: 38–48

    Article  PubMed  CAS  Google Scholar 

  92. Kleiner-Fisman G, Fisman DN. Risk factors for the development of pedal edema in patients using pramipexole. Arch Neurol 2007; 64: 820–4

    Article  PubMed  Google Scholar 

  93. Tan EK, Ondo W. Clinical characteristics of pramipexole-induced peripheral edema. Arch Neurol 2000; 57: 729–32

    Article  PubMed  CAS  Google Scholar 

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No sources of funding were used to assist in the preparation of this review. The author has no conflicts of interest that are directly relevant to the content of this review.

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Wood, L.D. Clinical Review and Treatment of Select Adverse Effects of Dopamine Receptor Agonists in Parkinson’s Disease. Drugs Aging 27, 295–310 (2010). https://doi.org/10.2165/11318330-000000000-00000

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