 |
 |
Dopamine Agonist Risk-Benefit Unclear in Parkinson's BIRMINGHAM, England, April 16 -- Despite some drawbacks with dopamine agonists, they seem better at controlling motor complications of early Parkinson's disease than levodopa, researchers here found in a meta-analysis. Action Points Explain to interested patients that treatment for Parkinson's disease has relied on levodopa for many years, but the drug has a range of motor side effects that are clinically important. This study confirms that the newer dopamine agonists are better at controlling the motor complications of the disease than levodopa. Note that the drugs have a range of other non-motor side effects that appear to be clinically important and the balance of risks and benefits remains unclear. The researchers characterized the 29 studies in the meta-analysis as of variable quality. Yet they found that dopamine agonists were less likely to lead to dyskinesia, dystonia, and motor fluctuations. The downside of the agents is that they are associated with an increase in side effects such as somnolence, hallucinations, and nausea, Rebecca Stowe, Ph.D., of the University of Birmingham, and colleagues reported in a Cochrane Review. And patients treated with dopamine agonists were more than twice as likely to stop therapy as were those treated with levodopa, wrote Dr. Stowe and colleagues. The high dropout rate suggests that "the side effects were severe enough to have a meaningful impact on patients' quality of life, outweighing the muscle control problems," Dr. Stowe said. The 29 studies in the meta-analysis included 5,247 patients who were in the early stages of Parkinson's disease. "The balance of risks and benefits of dopamine agonists remains unclear," Dr. Stowe said. A qualitative analysis suggested that levodopa did a better job treating the standard symptoms of Parkinson's, including bradykinesia, tremor, rigidity, and postural instability. The 29 studies had three main designs -- dopamine agonists versus placebo, agonists and levodopa against levodopa, and agonists alone against levodopa. Analysis of the outcomes of the studies showed that, compared with levodopa patients, participants treated with a dopamine agonist: Were half as likely to develop dyskinesia. The odds ratio was 0.51, with a 95% confidence interval from 0.43 to 0.59, which was significant at P0.00001. Had less dystonia. The odds ratio was 0.64, with a 95% confidence interval from 0.51 to 0.81, which was significant at P=0.0002. Were less likely to have motor fluctuations. The odds ratio was 0.75, with a 95% confidence interval from 0.63 to 0.90, which was significant at P=0.002. On the other hand, a range of non-motor complications was likely to be increased. Dopamine agonist patients were: Nearly four times as likely to have edema. The odds ratio was 3.68, with a 95% confidence interval from 2.62 to 5.18, which was significant at P0.00001. 51% more likely to have somnolence. The odds ratio was 1.49, with a 95% confidence interval from 1.12 to 2.00, which was significant at P=0.007. More prone to constipation, with an odds ratio of 1.59 with a 95% confidence interval from 1.11 to 2.28, which was significant at P=0.01. Likely to suffer dizziness, with an odds ratio of 1.45 and a 95% confidence interval from 1.09 to 1.92, which was significant at P=0.01. More subject to hallucinations. The odds ratio was 1.69, with a 95% confidence interval from 1.13 to 2.52, which was significant at P=0.01. More prone to nausea, with an odds ratio of 1.32 and a 95% confidence interval from 1.05 to 1.66, which was significant at P=0.02. They also noted that "symptomatic control of Parkinson's disease was better with levodopa than with agonists, but data were reported too inconsistently and incompletely to meta- analyze." Importantly, the researchers found, patients treated with dopamine agonists were also significantly more likely to stop treatment because of adverse events. The odds ratio was 2.49, with a 95% confidence interval from 2.08 to 2.98, which was significant at P0.00001. The analysis confirms that the benefit of the newer dopamine agonists, the researchers conclude, "provides conclusive evidence" of an increase in non-motor side-effects that were not obvious from individual clinical trials. Based on the high rate of treatment discontinuation, the non-motor side-effects "appear at least as clinically important" as the motor complications that the dopamine agonists avoid, the researchers said. They concluded that "unfortunately, the balance of risks and beneļ¬ts remains unclear, as only one trial included overall quality of life and cost-effectiveness as outcome measures." The researchers did not report any external or internal financing. Dr. Stowe and all but one of the researchers reported no conflicts. Carl E. Clarke, M.D., of the University of Birmingham, reported funding from manufacturers of several of the drugs discussed in the review. Primary source: Cochrane Database of Systematic Reviews Source reference: Stowe RL, et al "Dopamine agonist therapy in early Parkinson's disease"Cochrane Database of Systematic Reviews 2008; 2: CD006564. DOI: 10.1002/14651858.CD006564.pub2. Find this article at: http://www.medpagetoday.com/Neurology/ParkinsonsDisease/tb/9139 Click Here to Print ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn