Journal of Neurology

, Volume 257, Supplement 2, pp 262–267

Has drug therapy changed the natural history of Parkinson’s disease?



This narrative review examines the effects of drug therapy on the natural history of Parkinson’s disease. In terms of modifying the underlying disease process, it is possible that immediate therapy, rather than deferred treatment, can have a positive effect on the underlying disease process. However, it is unlikely that drug therapy has changed mortality from the condition and there is no evidence that it can delay the onset of non-motor features such as dementia and falls. The beneficial effects of drug therapy on the motor symptoms of Parkinson’s disease are unquestionable, but these are at the expense of short-term dopaminergic side effects, long-term motor complications, and impulse control disorders. Major questions remain regarding which initial therapeutic approach should be taken which may possibly be answered by the ongoing PD MED trial. The beneficial effects of drug therapy on the motor features of Parkinson’s disease have had a fundamental impact on the suffering of patients. The mainstay of these therapies continues to be levodopa, although it is now used at lower doses than in the past and in combination with other drug classes.


Parkinson’s disease Natural history Mortality Treatment Levodopa 


  1. 1.
    Clarke CE (1993) Mortality from Parkinson’s disease in England and Wales 1921–1989. J Neurol Neurosurg Psychiatry 56:690–693PubMedCrossRefGoogle Scholar
  2. 2.
    Clarke CE (1995) Does levodopa therapy delay death in Parkinson’s disease? A review of the evidence. Mov Disord 10(3):250–256PubMedCrossRefGoogle Scholar
  3. 3.
    Clarke C (2000) Mortality from Parkinson’s disease. J Neurol Neurosurg Psychiatry 68(2):254–255PubMedCrossRefGoogle Scholar
  4. 4.
    Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression, and mortality. Neurology 17:427–442PubMedGoogle Scholar
  5. 5.
    Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P (2003) Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol 60(3):387–392PubMedCrossRefGoogle Scholar
  6. 6.
    Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A et al (2004) Levodopa and the progression of Parkinson’s disease [see comment]. N Engl J Med 351(24):2498–2508PubMedCrossRefGoogle Scholar
  7. 7.
    Shoulson I, Oakes D, Fahn S, Lang A, Langston JW, LeWitt P et al (2002) Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson’s disease: a randomized placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of Parkinsonism trial. Ann Neurol 51(5):604–612PubMedCrossRefGoogle Scholar
  8. 8.
    Parkinson Study Group (2004) A controlled, randomised, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol 61:561–566CrossRefGoogle Scholar
  9. 9.
    Olanow CW, Rascol O, Hauser R, Feigin PD, Jankovic J, Lang A et al (2009) A double-blind, delayed-start trial of rasagiline in Parkinson’s disease. N Engl J Med 361(13):1268–1278PubMedCrossRefGoogle Scholar
  10. 10.
    Clarke CE (2008) Are delayed-start design trials to show neuroprotection in Parkinson’s disease fundamentally flawed? Mov Disord 23(6):784–789PubMedCrossRefGoogle Scholar
  11. 11.
    Stowe RL, Ives NJ, Clarke C, van Hilten J, Ferreira J, Hawker RJ et al (2008) Dopamine agonist therapy in early Parkinson’s disease. Cochrane Database Syst Rev (2):CD006564Google Scholar
  12. 12.
    Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE et al (2004) Monoamine oxidase type B inhibitors in early Parkinson’s disease: meta-analysis of 17 randomised trials involving 3525 patients. BMJ 329(7466):593PubMedCrossRefGoogle Scholar
  13. 13.
    Weintraub D (2008) Dopamine and impulse control disorders in Parkinson’s disease. Ann Neurol 64(Suppl 2):S93–S100PubMedGoogle Scholar
  14. 14.
    Schapira AH, Albrecht S, Barone P, Comella CL, McDermott MP, Mizuno Y et al (2010) Rationale for delayed-start study of pramipexole in Parkinson’s disease: the PROUD study. Mov Disord 25:1627–1632Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.School of Clinical and Experimental Medicine, College of Medicine and Dental SciencesUniversity of BirminghamBirminghamUK
  2. 2.Department of NeurologyCity Hospital, Sandwell and West Birmingham Hospitals NHS TrustBirminghamUK

Personalised recommendations