Drug Safety

, Volume 24, Issue 11, pp 863–868 | Cite as

Increased Risk of Somnolence with the New Dopamine Agonists in Patients with Parkinson’s Disease

A Meta-Analysis of Randomised Controlled Trials
  • Mahyar Etminan
  • Ali Samii
  • Bahi Takkouche
  • Paula A. Rochon
Original Research Article

Abstract

Background: Recent case reports and letters have alerted practitioners to the risk of sleep attacks, usually preceded by somnolence, in patients with Parkinson’s disease treated with pramipexole and ropinirole.

Objective: To quantify the risk of somnolence with the new dopamine agonists pramipexole and ropinirole in patients with Parkinson’s disease.

Methods: We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts and Cochrane Library, contacted experts and pharmaceutical manufacturers, and manually reviewed all references retrieved to identify possible articles to include. Information on randomisation, blinding, type of treatment and reporting of somnolence were abstracted by 2 independent reviewers. Disagreements were resolved by a third author.

Analysis: We made 2 separate analyses. The first analysis compared the risk of somnolence in patients taking either pramipexole or ropinirole to that in patients taking placebo. The second analysis compared the risk of somnolence with these drugs (plus levodopa) versus that with levodopa alone. We calculated pooled relative risk estimates using the random effects model and when no heterogeneity was detected we used the fixed effects model.

Results: Four trials were included in the analysis of patients taking pramipexole or ropinirole compared with those taking placebo. The pooled relative risk of somnolence in this analysis was 4.98 [95% confidence interval (CI) 1.79 to 13.89]. Seven trials were included in the analysis of patients taking levodopa and pramipexole or ropinirole compared with those taking levodopa alone. The pooled relative risk was 2.06 (95% CI 1.47 to 2.88).

Conclusion: Patients with Parkinson’s disease using pramipexole or ropinirole are at higher risk of experiencing somnolence relative to patients taking placebo. Patients taking levodopa plus either one of these dopamine agonists are at higher risk than those taking levodopa alone. Clinicians should carefully weigh this risk against the benefit of these agents when prescribing these drugs.

References

  1. 1.
    Adler CH, Sethi KD, Hauser RA, et al. Ropinirole for the treatment of early Parkinson’s disease. Neurology 1997; 49: 393–99PubMedCrossRefGoogle Scholar
  2. 2.
    Schrag AE, Brooks DJ, Brunt E, et al. The safety of ropinirole, a selective nonergoline dopamine agonist, in patients with Parkinson’s disease. Clin Neuropharmacol 1998; 21: 169–75PubMedGoogle Scholar
  3. 3.
    Lieberman A, Olanow CW, Sethi K, et al. A multicenter trial of ropinirole as adjunct treatment for Parkinson’s disease. Neurology 1998; 51: 1057–62PubMedCrossRefGoogle Scholar
  4. 4.
    Frucht S, Rogers JD, Greene PE, et al. Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology 1999; 52: 1908–10PubMedCrossRefGoogle Scholar
  5. 5.
    Piker W, Happe S. Sleep attacks in Parkinson’s disease. Lancet 2000; 356: 597–8CrossRefGoogle Scholar
  6. 6.
    Schapira AH. Sleep attacks (sleep episodes) with pergolide. Lancet 2000; 355: 1332–3PubMedCrossRefGoogle Scholar
  7. 7.
    Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson’s disease: a randomized controlled trial. JAMA 2000; 284: 1931–38Google Scholar
  8. 8.
    National Research Council. Combining information: statistical issues and opportunities for research. Washington, DC: National Academy Press, 1992: 52Google Scholar
  9. 9.
    Takkouche B, Cadarso-Suarez C, Spiegelman D. Evaluation of old and new tests of heterogeneity in epidemiologic metaanalysis. Am J Epidemiol 1999; 150: 206–15PubMedCrossRefGoogle Scholar
  10. 10.
    Rascol O, Lees AJ, Senard JM, et al. A placebo controlled study of ropinirole, a new D2 agonist in the treatment of motor fluctuations of L-dopa treated Parkinsonian patients. Adv Neurol 1996; 69: 531–34PubMedGoogle Scholar
  11. 11.
    Rascol O, Brooks DJ, Brunt ER, et al. Ropinirole in the treatment of early Parkinson’s disease: a six month interim report of a five year levodopa-controlled study. Mov Disord 1998; 13: 39–45PubMedCrossRefGoogle Scholar
  12. 12.
    Sethi KD, O’Brien CF, Hammerstad JP, et al. Ropinirole for the treatment of early Parkinson’s disease. Arch Neurol 1998; 55: 1211–6PubMedCrossRefGoogle Scholar
  13. 13.
    Parkinson Study Group. Safety and efficacy of pramipexole in early Parkinson’s disease: a randomized dose-ranging study. JAMA 1997; 278: 125–30Google Scholar
  14. 14.
    Shannon KM, Bennet JP, Friedman JH. Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson’s disease. Neurology 1997; 49: 724–28PubMedCrossRefGoogle Scholar
  15. 15.
    Brooks DJ, Abott RJ, Lee AJ, et al. A placebo-controlled evaluation of ropinirole, a novel D2 agonist, as sole dopaminergic therapy in Parkinson’s disease patients. Clin Neuropharmacol 1998; 21: 101–7PubMedGoogle Scholar
  16. 16.
    Brooks DJ, Torjanski N, Burn DJ. Ropinirole in the symptomatic treatment of Parkinson’s disease. J Neural Transplant 1995; 45Suppl. 1: 231–38Google Scholar
  17. 17.
    Pinter MM, Pogarell O, Oertel WH. Efficacy, safety and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson’s disease: a double blind, placebo, controlled, randomized, multicentre study. J Neurol Neurosurg Psychiatry 1999; 66: 436–1PubMedCrossRefGoogle Scholar
  18. 18.
    Rascol O, Lees AJ, Senard JM, et al. Ropinirole in the treatment of levodopa-induced motor fluctuations in patients with Parkinson’s disease. Clin Neuropharmacol 1996; 19: 234–45PubMedCrossRefGoogle Scholar
  19. 19.
    Rascol O, Brooks DJ, Korczyn AD, et al. A five year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. N Engl J Med 2000; 342: 1484–91PubMedCrossRefGoogle Scholar
  20. 20.
    Hauser RA, Gauger L, Anderson WM, et al. Pramipexole-induced somnolence and episodes of daytime sleep. Mov Disord 2000; 15: 658–63PubMedCrossRefGoogle Scholar
  21. 21.
    Frucht SJ, Greene PE, Fahn S. Sleep episodes in Parkinson’s disease: a wake up call. Mov Disord 2000; 15: 601–3PubMedCrossRefGoogle Scholar
  22. 22.
    British national formulary. 39th ed. Vol 1. London: British Medical Association, 2000Google Scholar
  23. 23.
    Canadian Pharmacists Association Group. In: Gillis MC, editor. Compendium of pharmaceuticals and specialties. 35th ed. Vol 1. Ottawa: Canadian Pharmacists Association, 2000Google Scholar
  24. 24.
    Physicians’ desk reference. 54th ed. Montvale (MI): Medical Economics Company, 2000Google Scholar
  25. 25.
    Corrigan MH, Denahan AQ, Eugene CW, et al. Comparison of pramipexole, fluoxetine and placebo in patients with major depression. Depress Anxiety 2000; 11: 58–65PubMedCrossRefGoogle Scholar
  26. 26.
    Ferreira JJ, Galitsky M, Montastruc JL, et al. Sleep attacks and Parkinson’s disease treatment. Lancet 2000; 355: 1333–4PubMedCrossRefGoogle Scholar
  27. 27.
    Olanow CW, Fahn S, Muenter M, et al. A multicenter double-blind placebo controlled trial of pergolide as an adjunct to sinemet in Parkinson’s disease. Mov Disord 1994; 9: 40–7PubMedCrossRefGoogle Scholar
  28. 28.
    Barone P, Bravi D, Bermejo-Pareja F, et al. Pergolide monotherapy in the treatment of early Parkinson’s disease: a randomized controlled study. Neurology 1999; 53: 573–9PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • Mahyar Etminan
    • 1
    • 2
  • Ali Samii
    • 3
  • Bahi Takkouche
    • 4
  • Paula A. Rochon
    • 1
    • 5
    • 6
  1. 1.Kunin-Lunenfeld Applied Research Unit, Department of PharmacyBaycrest Center for Geriatric CareToronto, OntarioCanada
  2. 2.Department of Clinical EpidemiologyUniversity of TorontoToronto, OntarioCanada
  3. 3.Department of Neurology, School of MedicineUniversity of WashingtonSeattleUSA
  4. 4.Department of Preventive Medicine, Faculty of MedicineUniversity of Santiago de CompostelaSantiago de CompostelaSpain
  5. 5.Departments of Medicine and Public Health Sciences, Faculty of MedicineUniversity of TorontoToronto, OntarioCanada
  6. 6.Institute for Clinical Evaluative SciencesSunnybrook and Women’s College Health Sciences CentreToronto, OntarioCanada

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