May 12 (HealthDay News) -- The drugs that are widely used to treat restless legs syndrome do provide relief, but they are burdened by side effects and a gradual loss of effectiveness that causes many sufferers to stop taking them, a new analysis finds.

"One of the things that we found that we can't fully explain is that they have more robust effects early in therapy," said study co-author C. Michael White, an associate professor of pharmacy practice at the University of Connecticut School of Pharmacy. The report was published in the May/June issue of the Annals of Family Medicine.

White and his colleagues looked at 14 trials of four nonergot dopamine agonist (NEDA) drugs, one of which never reached the market. The other three, pramipexole (Mirapex), ropinirole (Requip) and rotigotine (Neupro) are the mainstays of treatment for a condition that affects 5 percent to 10 percent of American adults.

"This kind of meta-analysis hasn't been done before," White said. "There have been lots of studies to assess their effects, but they didn't look at things like rates of withdrawal and risks associated with using the therapy."

Restless legs syndrome is a neurological disorder in which the leading symptom is described by its name. Those symptoms usually occur at night, interfering with sleep. NEDA drugs quiet the legs by mimicking the activity of dopamine, a molecule that acts as a hormone and also a signal transmitter between cells. Such drugs are also used to treat Parkinson's disease.

One drug that looked good in the meta-analysis was sumanirole, whose development was stopped in 2004 by Pfizer Inc. on the grounds that it offered no apparent advantage over existing medications. The meta-analysis included just one short-term study of sumanirole.

Among the others, White said, "when you look at the benefits of pramipexole, it looks like it's providing more benefits." One explanation for that finding is that the trials of the drug were relatively short-term, before the side effects that lead many participants to drop out became more evident, he said.

Those side effects include nausea, dizziness, wheeziness, fatigue and transient headache, White said.

The dropout rate was greatest in trials of ropinerole, "which may be the drug that is causing the most profound side effects," he said.

On the positive side of the ledger, "it looks like they all had the same measure of efficacy" in relieving symptoms, at least over the short-term, White said.

"It would be tempting to go with pramipexole, at least for the short term," he said. "If you are concerned about safety, ropinerole had a higher rate of withdrawal."

Some head-to-head studies of the drugs are needed to determine which is the most effective and safest, and such studies should have a longer follow-up than past studies, the researchers said.

The American College of Neurology is now going over the data on controlled trials of the NEDA drugs and will publish guidelines on their use "by the end of the year," said Dr. William Endo, an associate professor of neurology at Baylor College of Medicine in Houston.

Endo, a member of the committee developing the guidelines, said the published studies show that these are definitely first-line treatments for restless legs syndrome. There is no doubt about it, he said. These are the only really major compounds that have gone through controlled trials. It is the quality of the studies, as much as the results, that supports them.

The dropout rate among people taking the drugs is about what could be expected of any drug therapy, Endo said.

SOURCES: C. Michael White, Pharm.D., associate professor, pharmacy practice, University of Connecticut School of Pharmacy, Storrs; William Endo, associate professor, neurology, Baylor College of Medicine, Houston; May/June 2008 Annals of Family Medicine