Restless legs syndrome patients may need drug rotation

Periodic medication changes may be necessary to keep restless legs syndrome symptoms in check, according to a case report published in this month's Journal of General Internal Medicine. Physicians at the University of Rochester School of Medicine and Dentistry in New York documented the details of two patients who, in less than a year, required escalating doses of medication in order to control the condition. At some point, the drugs also started to make things worse, indicating the medication class should be switched.

"One cannot simply prescribe a single medication for RLS and expect long-term success," wrote the authors. "Patients with this condition often require careful clinical monitoring and frequent medication adjustments."

Several studies have found tolerance and augmentation rates ranging from 32% to 80%, depending on the drug class. Doctors also say it is something they see in their practices. But while its existence has been documented, it's unknown how to prevent it or predict who will experience it.

"There are a lot of questions that need to be answered," said Sudhansu Chokroverty, MD, professor and co-chair of neurology in charge of clinical neurophysiology and sleep medicine at the New Jersey Neuroscience Institute at JFK Medical Center.

Experts say, though, that it is possible to deal with these issues as they come up. Many specialists say using dopamine agonists rather than levodopa as first-line therapy can reduce the incidence of these types of events. Last month the Food and Drug Administration gave the nod to another dopamine agonist. Mirapex (pramipexole dihydrochloride), manufactured by Boehringer Ingelheim Pharmaceuticals, was approved for the treatment of the disorder's moderate to severe form. This drug was first approved in 1997 to treat Parkinson's.

Other strategies include addressing possible iron deficiency or changing medications for other conditions that could be making the situation worse. Splitting the dose throughout the day may reduce the chance of augmentation, and the dosage can be increased in response to tolerance, particularly if the patient starts at a low dose. The drug class can be changed completely or another medication added if necessary.

"These medications ... do have side effects, in this case augmentation and tolerance, but these are not insurmountable," said Clete Kushida, MD, PhD, director of the Stanford University Center for Human Sleep Research in Palo Alto, Calif.

But physicians pointed out that while tolerance and augmentation are common, it rarely happens as quickly as it did to this paper's subjects.

"Physicians should be aware of it, but most patients are not going to be like these," said Wayne Hening, MD, PhD, assistant clinical professor of neurology at the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School. "We usually find a medication that they will be happy with, and it's going to work for years."