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.
Similar content being viewed by others
References
Nussbaum RL, Ellis CE. Alzheimer’s disease and Parkinson’s disease. N Engl J Med 2003; 348: 1356–64
Factor SA, Weiner WJ, editors. Parkinson’s disease: diagnosis and clinical management. 2nd ed. New York: Demos, 2008
Fabbrini G, Brotchie JM, Grandas F, et al. Levodopa-induced dyskinesias. Mov Disord 2007; 22(10): 1379–89
Chen JJ, Swope DM. Pharmacotherapy for Parkinson’s disease. Pharmacotherapy 2007; 27: 161S–73S
Hubble JP. Long-term studies of dopamine agonists. Neurology 2002; 58Suppl. 1: S42–50
Reichmann H. Long-term treatment with dopamine agonists in idiopathic Parkinson’s disease. J Neurol 2000; 247Suppl. 4:IV/17–19
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
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
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
Poewe W. Non-motor symptoms in Parkinson’s disease. Eur J Neurol 2008; 15Suppl. 1: 14–20
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]
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]
Tan EK, Jankovic J. Choosing dopamine agonists in Parkinson’s disease. Clin Neuropharmacol 2001; 24(5): 247–53
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
Junghanns S, Glockler T, Reichmann H. Switching and combining of dopamine agonists. J Neurol 2004; 251Suppl. 6: VI/19–23
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
Reichmann H, Herting B, Muller A, et al. Switching and combining dopamine agonists. J Neural Transm 2003; 110: 1393–400
Clinical Pharmacology [database]. Tampa (FL): Gold Standard, Inc., 2009 [online]. Available from URL: http://www.clinicalpharmacology.com [Accessed 2009 Oct 14]
Parlodel® (bromocriptine mesylate tablets): US prescribing information. New York: Novartis, 2006
Mirapex® (pramipexole dihydrochloride tablets): US prescribing information. Ridgefield (CT): Boehringer Ingelheim Pharmaceuticals, Inc., 2009
Requip® (ropinirole tablets): US prescribing information. Research Triangle Park (NC): GlaxoSmithKline, 2009
Neupro® (rotigotine transdermal system): US prescribing information. Mequon (WI): Schwarz Pharma, LLC, 2004
Requip XL® (ropinirole extended release tablets): US prescribing information. Research Triangle Park (NC): GlaxoSmithKline, 2008
Stewart D, Morgan E, Burn D, et al. Dopamine agonist switching in Parkinson’s disease. Hosp Med 2004; 65(4): 215–9
Fahn S, Jankovic J, editors. Principles and practice of movement disorders. 2nd ed. Philadelphia (PA): Churchill Livingstone Elsevier, 2007
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
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
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
Voon V, Potenza MN, Thomsen T. Medication-related impulse control and repetitive behaviors in Parkinson’s disease. Curr Opin Neurol 2007; 20: 484–92
Friedman JH, Factor SA. Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson’s disease. Mov Disord 2000; 15(2): 201–11
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
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
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
Apokyn® (apomorphine hydrochloride injection): US prescribing information. Brisbane (CA): Tercica, Inc., 2009
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
Reddymasu SC, Soykan I, McCallum RW. Domperidone: review of pharmacology and clinical applications in gastroenterology. Am J Gastroenterol 2007; 102: 2036–45
Barone JA. Domperidone: a peripherally acting dopamine2-receptor antagonist. Ann Pharmacother 1999; 33: 429–40
Champion MC, Hartnett M, Yen M. Domperidone, a new dopamine antagonist. CMAJ 1986; 135: 457–61
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
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]
Berardi RR, editor. Handbook of nonprescription drugs: an interactive approach to self care. 15th ed. Washington, DC: American Pharmaceutical Association, 2006
Spirling LI, Daniels IR. Peppermint: more than just an after-dinner mint. J R Soc Promot Health 2001; 121(1): 62–3
Arnulf I. Excessive daytime sleepiness in parkinsonism. Sleep Med Rev 2005; 9: 185–200
Kumar R. Approved and investigational uses of modafinil: an evidence-based review. Drugs 2008; 68(13): 1803–39
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
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
Chou KL. Adverse events from the treatment of Parkinson’s disease. Neurol Clin 2008; 26: S65–83
Parkes JD. Domperidone and Parkinson’s disease. Clin Neuropharmacol 1986; 9(6): 517–32
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
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
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]
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
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
Brodsky MA, Godbold J, Roth T, et al. Sleepiness in Parkinson’s disease: a controlled study. Mov Disord 2003; 18(6): 668–72
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
Hogl B, Seppi K, Brandauer E. Increased daytime sleepiness in Parkinson’s disease: a questionnaire survey. Mov Disord 2003; 18(3): 319–23
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
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
Valentino RM, Foldvary-Schaefer N. Modafinil in the treatment of excessive daytime sleepiness. Cleve Clin J Med 2007; 74(8): 561–71
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
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
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
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
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
Weintraub D. Dopamine and impulse control disorders in Parkinson’s disease. Ann Neurol 2008; 64 Suppl.: S93–100
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
Grosset D. Dopamine agonists and therapy compliance. Neurol Sci 2008; 29: S375–6
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
Nirenberg MJ, Waters C. Compulsive eating and weight gain related to dopamine agonist use. Mov Disord 2006; 21(4): 524–9
Rabinak CA, Nirenberg MJ. Dopamine agonist withdrawal syndrome in Parkinson disease. Arch Neurol 2010; 67(1): 58–63
Barnes J, David AS. Visual hallucinations in Parkinson’s disease: a review and phenomenological survey. J Neurol Neurosurg Psychiatry 2001; 70: 727–33
Fenelon G, Mahieux F, Huon R, et al. Hallucinations in Parkinson’s disease: prevalence, phenomenology and risk factors. Brain 2000; 123: 733–45
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
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
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
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
Papapetropoulos S, Argyriou AA, Ellul J. Factors associated with drug-induced visual hallucinations in Parkinson’s disease. J Neurol 2005; 252: 1223–8
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
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
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
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
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
The French Clozapine Parkinson Study Group. Clozapine in drug-induced psychosis in Parkinson’s disease. Lancet 1999; 353: 2041–2
Senard JM, Rai S, Lapeyre-Mestre M. Prevalence of orthostatic hypotension in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997; 63: 584–9
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
Goldstein DS, Pechnik S, Holmes C, et al. Association between supine hypertension and orthostatic hypotension in autonomic failure. Hypertension 2003; 42: 136–42
Lang AE. Acute orthostatic hypotension when starting dopamine agonist therapy in Parkinson disease: the role of domperidone therapy [letter]. Arch Neurol 2001; 58: 835
Abate G, Polimeni RM, Cuccurullo F, et al. Effects of indomethacin on postural hypotension in Parkinsonism. BMJ 1979; 2: 1466–8
Hoehn MM. Levodopa-induced postural hypotension: treatment with fludrocortisone. Arch Neurol 1975; 32: 50–1
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
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
Kleiner-Fisman G, Fisman DN. Risk factors for the development of pedal edema in patients using pramipexole. Arch Neurol 2007; 64: 820–4
Tan EK, Ondo W. Clinical characteristics of pramipexole-induced peripheral edema. Arch Neurol 2000; 57: 729–32
Acknowledgements
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Published:
Issue Date:
DOI: https://doi.org/10.2165/11318330-000000000-00000