Many of the symptoms of Parkinson's disease are due to the loss of certain groups of nerves in the brain, which results in the lack of a chemical called dopamine. Currently, there are several different treatments available for people with newly diagnosed Parkinson's including levodopa (Sinemet or Madopar) which is converted into dopamine in the brain, dopamine agonists (for example, ropinirole and pramipexole) which mimic the action of dopamine, and monoamine oxidase B (MAO-B) inhibitors (selegiline or rasagiline) which reduce the breakdown of dopamine in the brain. Each of these types of drugs has theoretical advantages and disadvantages. For example, although a very good treatment, levodopa can cause involuntary movements (dyskinesia), painful cramps (dystonia) and a shortened response to each dose (motor fluctuations) after a while, whilst MAO-B inhibitors and dopamine agonists may reduce the risk of these complications but are not so good at improving the symptoms of Parkinson's. At present, therefore, it is not clear which of these three groups of drugs should be prescribed when people with early Parkinson's first need treatment. We reviewed the trials that compared giving MAO-B inhibitors with other types of medication in people with early Parkinson's to see if there was good evidence that MAO-B inhibitors were the best treatment to offer. However, unfortunately we only identified two trials (593 patients) so there was only limited evidence. The results showed that MAO-B inhibitors were less good at improving the symptoms of Parkinson's than either levodopa or dopamine agonists but that they may reduce motor fluctuations compared with levodopa, though not compared with dopamine agonists. MAO-B inhibitors did, however, have fewer major side effects than some dopamine agonists.
MAO-B inhibitors are one option for the early treatment of PD although they have weaker symptomatic effects than levodopa and dopamine agonists. They may reduce the rate of motor fluctuations compared with initial levodopa therapy and may have fewer significant adverse effects than the older agonists but data are too few to provide reliable conclusions.
It has been postulated that monoamine oxidase B (MAO-B) inhibitors alter disease progression in Parkinson's disease (PD) but trials have produced conflicting results.
To assess the effectiveness and safety of long-term use of MAO-B inhibitors compared with other dopaminergic agents in early PD.
We searched several electronic databases including: the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2009), MEDLINE (January 1950 to February 2009) and EMBASE (January 1980 to February 2009). We also handsearched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other researchers.
We included all randomised controlled trials that compared a MAO-B inhibitor with other dopaminergic agents (presently levodopa or dopamine agonists) in patients with early PD, where treatment and follow up lasted at least one year.
Two reviewers independently selected trials for inclusion, assessed the methodological quality, and extracted the data. Additional data were provided by the original authors. Random-effects models were used to analyse results, where appropriate.
Only two eligible trials were included (593 patients), both of reasonable quality although one was unblinded. Both trials compared selegiline with a dopamine agonist, whilst one also compared selegiline with levodopa. MAO-B inhibitors were not associated with a significant increase or decrease in deaths compared with levodopa (odds ratio (OR) 0.96; 95% confidence interval (CI) 0.52 to 1.76) or dopamine agonists (OR 1.30; 95% CI 0.69 to 2.45). Those receiving MAO-B inhibitors were more likely to require add-on therapy during follow-up than those receiving levodopa (OR 12.02; 95% CI 6.78 to 21.31) or dopamine agonist (OR 2.00; 95% CI 1.05 to 3.81). There was a reduction in motor fluctuations with MAO-B inhibitors compared with levodopa (OR 0.55; 95% CI 0.32 to 0.94) but not dopamine agonists (OR 1.15; 95% CI 0.65 to 2.05). Withdrawals due to adverse events were less common with MAO-B inhibitors than with dopamine agonists (OR 0.11; 95% CI 0.01 to 0.99).