Dopamine agonists for Parkinson's disease

Abstract

Sir—Yves Agid and colleagues (Aug 17, p 575) argue that levodopa is the most effective treatment for Parkinson’s disease and that the associated motor side-effects are related to the pulsatile delivery of this drug. They suggest that these complications can be prevented with long-acting dopaminergic medications or continuous infusion of levodopa. However, Agid and co-workers make no mention of the role of dopamine agonists as an alternative treatment strategy to levodopa in early disease. Many patients with Parkinson’s disease have motor complications, including dyskinesia, within 5–10 years of starting levodopa; these motor complications increase with the dose of levodopa. Dyskinesias are a particular problem in young-onset patients and are difficult to manage. Currently available controlled-release inhibitors of aromatic aminoacid decarboxylase are not proven to reduce levodopa-induced motor fluctuations in the long term. The alternative of continuous infusion is not a practical option for most patients with Parkinson’s disease. We do not know of any evidence that early use of inhibitors of aromatic aminoacid decarboxylase or catecholO-methyltransferase reduce motor complications. There is, however, evidence that dopamine agonists are associated with fewer motor sideeffects than standard levodopa therapy when treatment is started early in the disease. Preclinical studies suggest that dopamine agonists may reduce the loss of dopaminergic neurons, and slow the rate of disease progression. In double-blind trials with imaging endpoints, A Whone and colleagues and K Marek and co-workers noted that loss of dopamine-transporter function is significantly reduced with dopamine agonists compared with levodopa. We recommend that occurrence of motor complications can be kept to a minimum by use of a dopamine agonist in appropriate patients and by delaying introduction of levodopa in early disease to prevent neuronal priming to these effects. The objectives of management of Parkinson’s disease are changing—it is no longer appropriate just to provide short-term control of motor symptoms. The longer term objective to reduce all complications and ensure preservation of quality of life for as long as is possible is arguably of greater importance. The cognitive consequences of Parkinson’s disease remain a major concern for older patients, but we now have the opportunity to reduce the occurrence of motor complications associated with long-term levodopa therapy. The evidence is building in favour of offering dopamine agonists to all suitable patients from the onset of Parkinson’s disease.