Balance of risks and benefits unclear for dopamine agonist therapy in early Parkinson’s disease

Clinical question: 
Compared to placebo or levodopa, how effective and safe are dopamine agonists (DAs) in early Parkinson’s disease (PD)?
Bottom line: 
Compared to placebo or levodopa, DAs reduce motor complications (dystonia, dyskinesia and motor fluctuations) in patients with early PD1. However, symptom control is poorer with DAs, and ‘non-motor’ side-effects are increased (oedema, somnolence, constipation, dizziness, hallucinations, nausea and headaches). Patients on a DA were more than twice as likely to discontinue treatment prematurely due to adverse effects than control patients, suggesting that the ‘non-motor’ side-effects were of sufficient severity to have a meaningful impact on patient’s quality of life and were perhaps at least as clinically important as the motor complications.
Caveat: 
Unfortunately the balance of risks and benefits remains unclear, as only one trial included overall quality of life and cost-effectiveness as outcome measures. Larger, long-term comparative trials assessing patient-rated quality of life are needed to assess more reliably the balance of benefits and risks of DAs compared to levodopa. It is also important that cost-effectiveness is assessed, as there is a need for better evidence on the cost-effectiveness of the considerably more expensive DAs.
Context: 
Parkinson's disease is a progressive disorder affecting over six million people worldwide, making it the most common neurodegenerative disease after Alzheimer's disease2. In the absence of curative therapy, treatment is directed towards alleviating the characteristic symptoms of PD such as bradykinesia, tremor, rigidity and postural instability3. Levodopa combined with a peripheral dopa-decarboxylase inhibitor provides effective symptomatic control. However, long-term levodopa use is associated with the development of motor complications such as involuntary movements (dyskinesia) and motor fluctuations ('wearing-off' phenomenon and unpredictable 'on-off' fluctuations). Since levodopa was introduced in the 1960s, two other drug classes have also become widely used4. These are dopamine agonists and monoamine oxidase type B inhibitors (MAOBIs) and are used either alone (as first-line treatment) or in combination with levodopa, in an attempt to control symptoms or delay the onset of motor complications or both in early PD.
Review CD#: 
CD006564
PEARLS No: 
72
Date: 
May, 2008
Authored by: 
Brian R McAvoy