Definitions of the strength of the recommendations (A, B, C, U) and classification of the evidence (Class I through Class IV) are provided at the end of the "Major Recommendations" field.
Selegiline. What is the role of selegiline in the treatment of early Parkinson’s disease (PD)?
Conclusions
Selegiline has mild symptomatic benefit (class II). There is no convincing clinical evidence for neuroprotective benefit with selegiline (class II). There is no convincing evidence for increased mortality with selegiline whether it is given in combination with levodopa or as monotherapy (class II).
Recommendations for Patients with Parkinson's Disease Who Require Symptomatic Treatment
Initial symptomatic treatment of patients with Parkinson's disease with selegiline in order to confer mild, symptomatic benefit prior to the institution of dopaminergic therapy may be considered (level A, class II evidence).
There is insufficient evidence to recommend the use of selegiline to confer neuroprotection in patients with Parkinson's disease (level U).
Initiating dopaminergic treatment. When symptomatic therapy is required, does levodopa or a dopamine agonist offer best control of motor symptoms?
Conclusions
Levodopa, cabergoline, ropinirole, and pramipexole are effective in ameliorating motor and activities of daily living disability in patients with Parkinson's disease who require dopaminergic therapy.
Levodopa is more effective than cabergoline, ropinirole, and pramipexole in treating the motor and activities of daily living features of Parkinson's disease.
Initiating dopaminergic treatment. When symptomatic therapy is required, does levodopa or a dopamine agonist offer the most favorable long-term complication profile?
Conclusions
Cabergoline, ropinirole, and pramipexole treatment of Parkinson's disease patients requiring dopaminergic therapy results in fewer motor complications (wearing off, dyskinesias, on-off motor fluctuations) than levodopa treatment after 2.5 years of follow-up.
Cabergoline, ropinirole, and pramipexole treatment of Parkinson's disease patients requiring dopaminergic therapy is associated with more frequent adverse events including hallucinations, somnolence, and edema than levodopa therapy.
Recommendations
In patients with Parkinson's disease who require the initiation of dopaminergic treatment, either levodopa or a dopamine agonist may be used. The choice depends on the relative impact of improving motor disability (better with levodopa) compared with the lessening of motor complications (better with dopamine agonists) for each individual patient with Parkinson's disease (level A, class I and class II evidence).
Sustained-release versus immediate release levodopa: When initiating levodopa therapy, which formulation should be used—immediate-release or sustained-release levodopa?
Conclusions
When initiating therapy with levodopa, there is no difference in the rate of motor complications between immediate-release levodopa and sustained-release levodopa.
Recommendations
For patients with Parkinson's disease in whom levodopa treatment is being instituted, either an immediate-release or sustained-release preparation may be considered (level B, class II evidence).
Definitions:
Ratings for the Quality of the Evidence
- Class I. Prospective, randomized, controlled clinical trial with masked outcome assessment, in a representative population. The following are required: (a) primary outcome(s) is/are clearly defined; (b) exclusion/inclusion criteria are defined; (c) adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias; (d) relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences.
- Class II. Prospective matched group cohort study in a representative population with masked outcome assessment that meets a through d above OR a randomized controlled trial in a representative population that lacks one criteria a through d.
- Class III. All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment.
- Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion.
Definitions for the Strength of the Recommendations
- A. Established as effective, ineffective or harmful for the given condition in the specified population. Level A rating requires at least one convincing class I study or at least two consistent, convincing class II studies.
- B. Probably effective, ineffective or harmful for the given condition in the specified population. Level B rating requires at least one convincing class II study or at least three consistent class III studies.
- C. Possibly effective, ineffective or harmful for the given condition in the specified population. Level C rating requires at least two convincing and consistent class III studies.
- U. Data inadequate or conflicting; given current knowledge, treatment is unproven.
