Tweaking the treatment for restless legs
"The best drugs for restless leg syndrome sometimes can only work for a time. Then they boomerang."
Last Super Bowl, a TV commercial lauded the power of Requip (ropinirole), the first drug approved to treat restless leg syndrome, a condition whose signature feature is creepy-crawly leg sensations that interfere with sleep and rest in nearly 1 of every 10 adults.
But if taken too long, the drug can actually backfire, causing symptoms to worsen, say doctors who specialize in treating the condition. They say that treatment that rotates through different types of medications may be needed for many patients.
"It’s impossible to tell the whole story in a TV spot just a few seconds long," said Irene Richard, M.D, a movement disorder neurologist at the University of Rochester Medical Center. "When patients come in asking about the treatment, doctors need to know that this is usually not a simple, single-pill solution, despite what they’ve seen on TV."
In an article published in the December issue of the Journal of General Internal Medicine, Richard and fellow neurologist Roger Kurlan, M.D., warn primary care physicians that they cannot expect long-term success by simply prescribing ropinirole or a similar medication in its class, which works by activating dopamine receptors in the brain. Instead, the team – experts at treating movement disorders like Parkinson’s disease, Tourette’s syndrome and restless leg syndrome – recommends that physicians may need to rotate some patients through these drugs along with different types of medications.
"The truth is, some of the most common, most effective drugs, including ropinirole and pramipexole, which was recently approved to treat restless leg syndrome, may only work effectively for each person for a limited time," Kurlan said. "After that, this class of drugs – albeit the most-popular, effective, and the only one approved by the Food and Drug Administration for restless leg syndrome– has a regrettable tendency to turn traitor. The medicine can actually begin to worsen symptoms."
In their paper, which was written together with nurse practitioner Cheryl Deeley, Richard and Kurlan examine the cases of two older women who have the syndrome. Typically, patients move their legs frequently and are often irked by a life of pacing in the wee morning hours, or in the worst cases, being unable to take road trips or even sit through a movie.
In both cases, and in most other patients the doctors have treated, they have found it helpful to switch the medications that patients receive. Sometimes the medication is no longer useful or helpful. But more often, the approved medications actually began to trigger the symptoms they were supposed to prevent, a phenomenon called augmentation. Richard and Kurlan have seen several patients whose symptoms eased immediately after treatment with the new medications began, but whose symptoms then worsened markedly later.
"At this point, you can’t just up the dose," Kurlan said, "The drug is part of the problem."
Augmentation is similar to what occurs when patients use painkillers for an extended period of time to treat their tension headaches. Soon, the medication actually triggers the headaches and worsens them. That’s why such painkillers, though effective in the short term, usually can’t be taken regularly and indefinitely without a painful price.
In their report, the doctors say that the new medication for restless leg syndrome worked in one of the patients for seven months before she had to be switched to other medications. In the other, it worked for a few years before switching was required.
In the wake of FDA approval for Requip and Mirapex (pramipexole), along with the attendant heavy advertising, Kurlan and Richard stress the importance to both primary care physicians and patients alike of understanding the risks of relying on these medications for too long.
"The best drugs for restless leg syndrome sometimes can only work for a time. Then they boomerang," said Kurlan.
The solution, Kurlan and Richard say, might be to switch things up at just the right time, rotating treatment through several different classes of drugs as problems arise, or perhaps before augmentation even appears. Finessing an ideal rotation is a challenge because it differs from one patient to the next. How long each medication should be used – or not used, a break called a "drug holiday" which may later allow doctors to use them again, effectively – are questions that should be looked at, the doctors say. In one of the cases covered in the report in the Journal of General Internal Medicine, a short break from the new medications allowed doctors to use them effectively for four more months, while in the other, the break afforded just two more months of relief before the patient needed to again be switched to another treatment.
Previous studies typically have not monitored for the problem of augmentation or have been too brief to observe it, but the team hopes more attention will be paid to the issue in research studies.
"Ultimately, there is hope for those who suffer from restless leg syndrome," Richard said. "But until there’s an effective drug we can use long term without interruption, for many patients hope lies in a merry-go-round of medications, not a single drug. Patients and physicians must be braced for this."
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