The causative relationship between
levodopa and the long-term motor complications of
therapy, along with the possibility that
levodopa may be toxic to dopaminergic neurones in vivo, has led to a move away from its use in early
Parkinson's disease. Alternatives such as
amantadine and the
anticholinergics suffer from poor efficacy in comparison and a high side effect profile.
Selegiline is probably less effective than
levodopa and the issue of its safety versus neuroprotective properties remains unresolved. Long-term trials with the old and newer
dopamine agonists as monotherapy have shown that as a class they can delay the development of
dyskinesia and probably response fluctuations. However, major uncertainties remain about their use as monotherapy in all patients instead of
levodopa. No data on their effect on quality of life and health care costs are available. Most of the trials were heavily biased towards younger patients with
Parkinson's disease, so little data in the elderly are available. In later disease when patients have already developed motor complications on
levodopa, the choice rests between adjuvant
therapy with a
dopamine agonist, a
catechol-O-methyltransferase inhibitor (COMT; e.g.
entacapone), and a
monoamine oxidase B inhibitor (MAO B; e.g.
selegiline). Trials with the former two classes have confirmed that they can reduce 'off' time, reduce
levodopa dose, and improve motor impairments and disabilities with acceptable increases in adverse events including
dyskinesia. Trials with
selegiline as adjuvant
therapy were less rigorous but it can allow a reduction in
levodopa dose and motor impairments. No studies have compared these three classes of
drug as adjuvant
therapy so there is no evidence on which to base rational decisions in this type of patient. A large pragmatic trial which includes older patients is needed to clarify which treatment is best for different stages of the disease.