Practice parameter: Initiation of treatment for Parkinson’s disease: An evidence-based review

In 1993, the last AAN Practice Parameter on medical treatment of Parkinson’s disease (PD) concluded that levodopa was the most effective drug for management of this disorder. Since then, a number of new compounds including non-ergot dopamine agonists (DA) and sustained-release levodopa have been released and studied. Thus, the issue of treatment in de novo PD patients warrants reexamination. Specific questions include: 1) does selegiline offer neuroprotection; 2) what is the best agent with which to initiate symptomatic treatment in de novo PD; and 3) is there a benefit of sustained release levodopa over immediate-release levodopa? Using evidence-based principles, a literature review using MEDLINE, EMBASE, and the Cochrane Library was performed to identify all human trials in de novo PD between 1966 and 1999. Only articles that fulfilled class I or class II evidence were included. Based on this review, the authors conclude: 1) Selegiline has very mild symptomatic benefit (level A, class II evidence) with no evidence for neuroprotective benefit (level U, class II evidence). 2) For PD patients requiring initiation of symptomatic therapy, either levodopa or a DA can be used (level A, class I and class II evidence). Levodopa provides superior motor benefit but is associated with a higher risk of dyskinesia. 3) No evidence was found that initiating treatment with sustained-release levodopa provides an advantage over immediate-release levodopa (level B, class II evidence).

[1]  V. Kostic,et al.  Early development of levodopa‐induced dyskinesias and response fluctuations in young‐onset Parkinson's disease , 1991, Neurology.

[2]  E. Tolosa,et al.  Immediate-release and controlled-release carbidopa/levodopa in PD , 1999, Neurology.

[3]  Cerebrospinal fluid homovanillic acid in the DATATOP study on Parkinson's disease. Parkinson Study Group. , 1995, Archives of neurology.

[4]  T. Engber,et al.  Palliative and prophylactic benefits of continuously administered dopaminomimetics in Parkinson's disease. , 1994, Neurology.

[5]  J. Montastruc Treatment of Parkinson's disease should begin with a dopamine agonist , 2000, Movement disorders : official journal of the Movement Disorder Society.

[6]  C. Mytilineou,et al.  Deprenyl Protects Dopamine Neurons from the Neurotoxic Effect of 1‐Methyl‐4‐Phenylpyridinium Ion , 1985, Journal of neurochemistry.

[7]  L. Grégoire,et al.  Risk Factors for Peak Dose Dyskinesia in 100 Levodopa-treated Parkinsonian Patients , 1996, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[8]  O. Rascol,et al.  Treatment of Parkinson's disease should begin with a dopamine agonist , 1999, Movement disorders : official journal of the Movement Disorder Society.

[9]  Anthony E. Lang,et al.  Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP patients requiring levodopa , 1996 .

[10]  A. Lees,et al.  Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson's disease , 1995, BMJ.

[11]  W. Oertel,et al.  Costs of drug treatment in Parkinson's disease , 1998, Movement disorders : official journal of the Movement Disorder Society.

[12]  R. Detels,et al.  A case‐control study of multiple sclerosis , 1989, Neurology.

[13]  J. Nutt On‐off phenomenon: Relation to levodopa pharmacokinetics and pharmacodynamics , 1987, Annals of neurology.

[14]  H. Przuntek,et al.  Effect of selegiline on mortality in patients with Parkinson's disease , 1998, Neurology.

[15]  A. Siderowf,et al.  Cost‐effectiveness analysis in Parkinson's disease: Determining the value of interventions , 2000, Movement disorders : official journal of the Movement Disorder Society.

[16]  Shoulson Mortality in DATATOP: A Multicenter trial in early Parkinson's disease , 1998, Annals of neurology.

[17]  U. Rinne Lisuride, a dopamine agonist in the treatment of early Parkinson's disease , 1989, Neurology.

[18]  L A Beckett,et al.  Prevalence of parkinsonian signs and associated mortality in a community population of older people. , 1996, The New England journal of medicine.

[19]  M. Mark,et al.  An analysis of treatment options and outcome in patients with Parkinson's disease and severe dyskinesias. , 1994, Annals of clinical and laboratory science.

[20]  C. Marsden,et al.  Cabergoline in the treatment of early parkinson's disease , 1997, Neurology.

[21]  Anthony E. Lang,et al.  Effect of deprenyl on the progression of disability in early Parkinson's disease. , 1989, The New England journal of medicine.

[22]  W. Weiner The initial treatment of Parkinson's disease should begin with levodopa , 1999, Movement disorders : official journal of the Movement Disorder Society.

[23]  D. Brooks,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. , 2000, The New England journal of medicine.

[24]  J. Montastruc,et al.  Long-term treatment of Parkinson's disease with bromocriptine. , 1979, Journal of neurology, neurosurgery, and psychiatry.

[25]  Dr Ira Shoulson Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP subjects not requiring levodopa , 1996, Annals of neurology.

[26]  John Seibyl,et al.  Pramipexole vs levodopa as initial treatment for Parkinson disease: A randomized controlled trial. Parkinson Study Group. , 2000, JAMA.

[27]  A. Burstein,et al.  Impact of Parkinson's disease and its pharmacologic treatment on quality of life and economic outcomes. , 2000, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[28]  M. Brin,et al.  Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. , 1993, The New England journal of medicine.

[29]  R. Palm,et al.  Selegiline delays the onset of disability in de novo parkinsonian patients , 1998, Neurology.

[30]  Bromocriptine in Parkinson's disease: a double-blind study comparing "low-slow" and "high-fast" introductory dosage regimens in de novo patients. UK Bromocriptine Research Group. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[31]  J. Kulisevsky,et al.  A Six‐month Study of Pergolide and Levodopa in De Novo Parkinson's Disease Patients , 1998, Clinical neuropharmacology.