Search tips
Search criteria 


Logo of jnnpsycJournal of Neurology, Neurosurgery and PsychiatryVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
J Neurol Neurosurg Psychiatry. 1994 September; 57(9): 1034–1038.
PMCID: PMC1073123

A randomised controlled study comparing bromocriptine to which levodopa was later added, with levodopa alone in previously untreated patients with Parkinson's disease: a five year follow up.


This pilot study was performed to compare the occurrence of long term motor complications in Parkinson's disease when the introduction of levodopa was delayed by an initial treatment with high doses of bromocriptine alone. The trial was a prospective randomised controlled study comparing 31 previously untreated patients with Parkinson's disease initially given bromocriptine alone to which levodopa was later added (group B/D) and 29 other previously untreated patients with Parkinson's disease immediately given levodopa alone (group D). The end point was the occurrence of the first motor complications (wearing off or dyskinesia). Group B/D patients received bromocriptine (52 (SEM 5) mg/day) for 2.7 years, to which levodopa was later added (471 (SEM 46) mg/day). Group D patients received a comparable dose of levodopa alone (569 (SEM 47) mg/day). Both had similar disability scores at the end of the study. Motor complications were fewer and appeared later in group B/D than in group D (56% after 4.9 (SEM 0.5) years of treatment v 90% after 2.7 (SEM 0.5) years, p < 0.01). Wearing off appeared later (p < 0.01) in group B/D (4.5 (SEM 0.6) years) than in group D (2.9 (SEM 0.6) years). Peak dose dyskinesia occurred less often in group B/D patients (three v 14 cases, p < 0.01). This study showed that a three year initial monotherapy with high doses of bromocriptine followed by addition of levodopa delayed the occurrence of long term motor complications usually found in patients with Parkinson's disease treated with levodopa alone from the beginning.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (997K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Marsden CD, Parkes JD. "On-off" effects in patients with Parkinson's disease on chronic levodopa therapy. Lancet. 1976 Feb 7;1(7954):292–296. [PubMed]
  • Montastruc JL. Recent advances in the clinical pharmacology of Parkinson's disease. Therapie. 1991 Jul-Aug;46(4):293–303. [PubMed]
  • Cedarbaum JM, Gandy SE, McDowell FH. "Early" initiation of levodopa treatment does not promote the development of motor response fluctuations, dyskinesias, or dementia in Parkinson's disease. Neurology. 1991 May;41(5):622–629. [PubMed]
  • Peppe A, Dambrosia JM, Chase TN. Risk factors for motor response complications in L-dopa-treated parkinsonian patients. Adv Neurol. 1993;60:698–702. [PubMed]
  • Horstink MW, Zijlmans JC, Pasman JW, Berger HJ, Korten JJ, van 't Hof MA. Which risk factors predict the levodopa response in fluctuating Parkinson's disease? Ann Neurol. 1990 May;27(5):537–543. [PubMed]
  • Caraceni T, Scigliano G, Musicco M. The occurrence of motor fluctuations in parkinsonian patients treated long term with levodopa: role of early treatment and disease progression. Neurology. 1991 Mar;41(3):380–384. [PubMed]
  • Horstink MW, Zijlmans JC, Pasman JW, Berger HJ, van't Hof MA. Severity of Parkinson's disease is a risk factor for peak-dose dyskinesia. J Neurol Neurosurg Psychiatry. 1990 Mar;53(3):224–226. [PMC free article] [PubMed]
  • de Jong GJ, Meerwaldt JD, Schmitz PI. Factors that influence the occurrence of response variations in Parkinson's disease. Ann Neurol. 1987 Jul;22(1):4–7. [PubMed]
  • Fahn S, Bressman SB. Should levodopa therapy for Parkinsonism be started early or late? Evidence against early treatment. Can J Neurol Sci. 1984 Feb;11(1 Suppl):200–205. [PubMed]
  • Melamed E. Initiation of levodopa therapy in parkinsonian patients should be delayed until the advanced stages of the disease. Arch Neurol. 1986 Apr;43(4):402–405. [PubMed]
  • Markham CH, Diamond SG. Modification of Parkinson's disease by long-term levodopa treatment. Arch Neurol. 1986 Apr;43(4):405–407. [PubMed]
  • Rinne UK. Combined bromocriptine-levodopa therapy early in Parkinson's disease. Neurology. 1985 Aug;35(8):1196–1198. [PubMed]
  • Rinne UK. Early combination of bromocriptine and levodopa in the treatment of Parkinson's disease: a 5-year follow-up. Neurology. 1987 May;37(5):826–828. [PubMed]
  • Weiner WJ, Factor SA, Sanchez-Ramos JR, Singer C, Sheldon C, Cornelius L, Ingenito A. Early combination therapy (bromocriptine and levodopa) does not prevent motor fluctuations in Parkinson's disease. Neurology. 1993 Jan;43(1):21–27. [PubMed]
  • Factor SA, Weiner WJ. Early combination therapy with bromocriptine and levodopa in Parkinson's disease. Mov Disord. 1993 Jul;8(3):257–262. [PubMed]
  • Montastruc JL, Rascol O, Rascol A. A randomised controlled study of bromocriptine versus levodopa in previously untreated Parkinsonian patients: a 3 year follow-up. J Neurol Neurosurg Psychiatry. 1989 Jun;52(6):773–775. [PMC free article] [PubMed]
  • Montastruc JL, Rascol O, Rascol A. Comparaison de la bromocriptine et de la levodopa dans le traitement de première intention de la maladie de Parkinson: résultats à 3 ans d'une étude prospective randomisée. Rev Neurol (Paris) 1990;146(2):144–147. [PubMed]
  • Gibb WR, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry. 1988 Jun;51(6):745–752. [PMC free article] [PubMed]
  • Golbe LI, Davis PH, Schoenberg BS, Duvoisin RC. Prevalence and natural history of progressive supranuclear palsy. Neurology. 1988 Jul;38(7):1031–1034. [PubMed]
  • Quinn N. Multiple system atrophy--the nature of the beast. J Neurol Neurosurg Psychiatry. 1989 Jun;Suppl:78–89. [PMC free article] [PubMed]
  • Gibb WR, Lees AJ. A comparison of clinical and pathological features of young- and old-onset Parkinson's disease. Neurology. 1988 Sep;38(9):1402–1406. [PubMed]
  • Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967 May;17(5):427–442. [PubMed]
  • Obeso JA, Grandas F, Vaamonde J, Luquin MR, Artieda J, Lera G, Rodriguez ME, Martinez-Lage JM. Motor complications associated with chronic levodopa therapy in Parkinson's disease. Neurology. 1989 Nov;39(11 Suppl 2):11–19. [PubMed]
  • Lees AJ. The on-off phenomenon. J Neurol Neurosurg Psychiatry. 1989 Jun;Suppl:29–37. [PMC free article] [PubMed]
  • Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br J Cancer. 1977 Jan;35(1):1–39. [PubMed]
  • Mouradian MM, Heuser IJ, Baronti F, Fabbrini G, Juncos JL, Chase TN. Pathogenesis of dyskinesias in Parkinson's disease. Ann Neurol. 1989 May;25(5):523–526. [PubMed]
  • Nutt JG. Levodopa-induced dyskinesia: review, observations, and speculations. Neurology. 1990 Feb;40(2):340–345. [PubMed]
  • Fabbrini G, Mouradian MM, Juncos JL, Schlegel J, Mohr E, Chase TN. Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part I. Ann Neurol. 1988 Sep;24(3):366–371. [PubMed]
  • Nakanishi T, Kanazawa I, Iwata M, Goto I, Kowa H, Mannen T, Mizuno Y, Nishitani H, Ogawa N, Takahashi A, et al. Nation-wide collaborative study on the long-term effects of bromocriptine in the treatment of parkinsonian patients: analysis on the maintenance and the change of the original mode of treatment. Eur Neurol. 1992;32 (Suppl 1):23–29. [PubMed]
  • Lees AJ, Stern GM. Sustained bromocriptine therapy in previously untreated patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 1981 Nov;44(11):1020–1023. [PMC free article] [PubMed]
  • Bédard PJ, Mancilla BG, Blanchette P, Gagnon C, Di Paolo T. Levodopa-induced dyskinesia: facts and fancy. What does the MPTP monkey model tell us? Can J Neurol Sci. 1992 Feb;19(1 Suppl):134–137. [PubMed]
  • Przuntek H, Welzel D, Blümner E, Danielczyk W, Letzel H, Kaiser HJ, Kraus PH, Riederer P, Schwarzmann D, Wolf H, et al. Bromocriptine lessens the incidence of mortality in L-dopa-treated parkinsonian patients: prado-study discontinued. Eur J Clin Pharmacol. 1992;43(4):357–363. [PubMed]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group