Medication Strategies for Slowing the Progression of Parkinson’s Disease

  • J. Eric Ahlskog
Part of the Current Clinical Practice book series (CCP)


The recognition that levodopa therapy is capable of reversing the symptoms and signs of Parkinson’s disease (PD) revolutionized the treatment of this disorder. It was soon recognized, however, that the disease continues to progress despite levodopa treatment. This progression is not rapid but occurs over many years. Potentially, there are three avenues of progression, and they occur to variable degrees (Table 7-1). In the first are levodopa treatment complications, including motor fluctuations and involuntary movements (dyskinesias). These motor fluctuations reflect a short-duration response to a dose of levodopa, with the improvement in motor symptoms lasting from 1 hour to a few hours and then “wearing off.” A transition from one state to the other may occur very rapidly in some patients; this has been termed the “on-off’ response. These levodopa treatment complications typically occur later in the course of the disease, at least in most cases. The second avenue of progression is a declining motor response to levodopa therapy; treatment may become much less effective with the passage of time. This is not necessarily a problem for all patients, and many have a relatively preserved levodopa response that persists for many years. The third avenue of progression is the development of problems not related to motor control. Dementia occurs in approximately 10% to 30% of patients with advancing disease. Psychosis may also develop with advancing disease, occurring as delusions, hallucinations, or inappropriate behavior. This may be provoked by medications, but in some cases psychosis is independent of drug therapy. Symptoms of dysautonomia, which may be present to a mild degree early in the course,


Substantia Nigra Motor Fluctuation Levodopa Treatment Slow Disease Progression Parkinson Study Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Selected Reading

  1. Ahlskog JE. Treatment of early Parkinson’s disease: are complicated strategies justified? Mayo Clin Proc 1996; 71: 659–670.PubMedCrossRefGoogle Scholar
  2. Beal MF. Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Ann Neurol 1992; 31: 119–130.PubMedCrossRefGoogle Scholar
  3. Blandini F, Porter RH, Greenamyre JT. Glutamate and Parkinson’s disease. Mol Neurobiol 1996; 12: 73–94.PubMedCrossRefGoogle Scholar
  4. Diamond SG, Markham CH, Hoehn MM, McDowell FH, MuenterMD. Multi-center study of Parkinson mortality with early versus later dopa treatment. Ann Neurol 1987; 22: 8–12.PubMedCrossRefGoogle Scholar
  5. Fahn S, Cohen G. The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it. Ann Neurol 1992; 32: 804–812.PubMedCrossRefGoogle Scholar
  6. Lees AJ. Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson’ s disease. Parkinson’ s Disease.Research Group of the United Kingdom. BMJ 1995; 311: 1602–1607.PubMedCrossRefGoogle Scholar
  7. Lesser RP, Fahn S, Snider SR, Cote LJ, Isgreen WP, Barrett RE. Analysis of the clinical problems in parkinsonism and the complications of long-term levodopa therapy. Neurology 1979; 29: 1253–1260.PubMedCrossRefGoogle Scholar
  8. Markham CH, Diamond SG. Long-term follow-up of early dopa treatment in Parkinson’ s disease. Ann Neurol 1986; 19: 365–372.PubMedCrossRefGoogle Scholar
  9. Olanow CW, Hauser RA, Gauger L, Malapira T, Koller W, Hubble J, Bushenbark K, Lilienfeld D, Esterlitz J. The effect of deprenyl and levodopa on the progression of Parkinson’ s disease. Ann Neurol 1995; 38: 771–777.PubMedCrossRefGoogle Scholar
  10. Palhagen S, Heinonen EH, Hagglund J, Kaugesaar T, Kontants H, Maki-Ikola O, Palm R, Turunen J. Selegiline delays the onset of disability in de novo parkinsonian patients. Swedish Parkinson Study Group. Neurology 1998; 51: 520–525.PubMedCrossRefGoogle Scholar
  11. The Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’ s disease. N Engl J Med 1993; 328: 176–183.CrossRefGoogle Scholar
  12. The Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP subjects not requiring levodopa. Ann Neurol 1996a; 39: 29–36.CrossRefGoogle Scholar
  13. The Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP patients requiring levodopa. Ann Neurol 1996b; 39: 37–45.CrossRefGoogle Scholar
  14. Poewe WH, Lees AJ, Stern GM. Low-dose L-dopa therapy in Parkinson’s disease: a 6-year follow-up study. Neurology 1986; 36: 1528–1530.PubMedCrossRefGoogle Scholar
  15. Przuntek H, Wetzel D, Blümner E, Danielczyk W, Letzel H, Kaiser HJ, Kraus PH, Riederer P, Schwarzmann D, Wolf H, Überla K. Bromocriptine lessens the incidence of mortality in L-Dopa-treated parkinsonian patients: prado-study discontinued. Eur J Clin Pharmacol 1992; 43: 357–363.PubMedCrossRefGoogle Scholar
  16. Rinne UK. Dopamine agonists as primary treatment in Parkinson’s disease. Adv Neurol 1986; 45: 519–523.Google Scholar
  17. Snyder SH, D’ Amato RI. MPTP: a neurotoxin relevant to the pathophysiology of Parkinson’s disease. The 1985 George C. Cotzias lecture. Neurology 1986; 36: 250–258.PubMedCrossRefGoogle Scholar
  18. Uitti RJ, Rajput AH, Ahlskog JE, Offord KP, Schroeder DR, Ho MM, Prasad M, Rajput A, Basran P. Amantadine treatment is an independent predictor of improved survival in Parkinson’s disease. Neurology 1996; 46: 1551–1556.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • J. Eric Ahlskog

There are no affiliations available

Personalised recommendations