Journal of Neural Transmission

, Volume 103, Issue 6, pp 699–715

Early institution of bromocriptine in Parkinson's disease inhibits the emergence of levodopa-associated motor side effects. Long-term results of the PRADO study

  • H. Przuntek
  • D. Welzel
  • M. Gerlach
  • E. Blümner
  • W. Danielczyk
  • H. -J. Kaiser
  • P. H. Kraus
  • H. Letzel
  • P. Riederer
  • K. Überla
Parkinson's Disease and Allied Conditions

DOI: 10.1007/BF01271230

Cite this article as:
Przuntek, H., Welzel, D., Gerlach, M. et al. J. Neural Transmission (1996) 103: 699. doi:10.1007/BF01271230

Summary

Long-term levodopa treatment in Parkinson's disease is typically associated with “motor side effects” consisting in dyskinesias and/or fluctuations in motility referred to as the on-off phenomena. The main objective of this prospective, randomized, multi-centre study was to determine to what extent the development of such complications could be prevented by partial substitution of levodopa monotherapy (L-DOPA/benserazide) by bromocriptine in patients with early symptoms of the disease. The basic trial population included 674 newly diagnosed Parkinsonian patients that were randomly allocated to monotherapy with levodopa or a combination therapy based upon a nearly 40% replacement of levodopa by bromocriptine. The two target regimens had to be consistently maintained for 42 months. Parkinsonian symptoms were assessed by means of the Webster rating scale, the Hoehn and Yahr scale, and the Zung Self-Rating Depression scale. Motor side effects and adverse events were recorded at each regular clinic visit.

Neurological symptoms improved and stabilized in a similar manner during treatment with both regimens throughout the study period. Motor side effects were observed in more patients on levodopa alone than on combination therapy (28.8 vs 20%; p=0.008). According to Kaplan-Meier estimates the cumulative probability of experiencing motor side effects was 0.43 on monotherapy, compared to 0.28 on combination therapy, which was equal to a one third reduction of risk (p=0.025). In regard to motor side effects, the degree of substitution of levodopa proved relevant: patients with >50% substitution by bromocriptine exhibited half the risk observed in those with <30% (p=0.045). The overall burden of motor side effects, as reflected by a sum score based upon the relevance, the severity and the extent of motor dysfunction, was also significantly less on combination therapy (p=0.046).

In conclusion, partial substitution of levodopa by bromocriptine (>30%) as first-line treatment of Parkinson's disease proves active in the prophylaxis of levodopa associated motor side effects. Early combination therapy therefore extends the period of optimal disease control.

Keywords

Parkinson's disease bromocriptine L-DOPA levodopa motor fluctuations adverse effects early combination therapy long-term treatment 

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • H. Przuntek
    • 1
  • D. Welzel
    • 2
  • M. Gerlach
    • 1
    • 4
  • E. Blümner
    • 5
  • W. Danielczyk
    • 6
  • H. -J. Kaiser
    • 3
  • P. H. Kraus
    • 1
  • H. Letzel
    • 5
  • P. Riederer
    • 4
  • K. Überla
    • 7
  1. 1.Neurologische KlinikRuhr-Universität, St. Josef-HospitalBochum
  2. 2.Institut für PharmakologieUniversität RegensburgGermany
  3. 3.Sandoz AGNuremberg
  4. 4.Klinische NeurochemieUniversitäts-NervenklinikWürzburg
  5. 5.Staticon, Medizinische Forschungsgesellschaft mbHPlaneggGermany
  6. 6.Neurologische AbteilungPflegeheim der Stadt Wien-Lainz, Ludwig-Boltzmann-Institut für AltersforschungViennaAustria
  7. 7.Institut für Medizinische Informationsverarbeitung, Biometrie und EpidemiologieUniversität MünchenGermany

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