The most commonly used treatments for WED/RLS make a bad disease worse

new England JournalStudy sheds light on treatment for Willis-Ekbom disease (Restless Legs (RLS) syndrome): Pregabalin (Lyrica) found as effective as FDA-approved pramipexole (Mirapex) without causing the worsening of symptoms that commonly occurs with pramipexole.

Rochester, Minn. – February 20, 2014 – A large-scale study of treatment for Willis-Ekbom disease (Restless Legs (RLS) syndrome, or WED/RLS) published February 14 in theNew England Journal of Medicine shows that the drug pregabalin (Lyrica) controls symptoms as well as pramipexole (Mirapex), but with significantly lower incidence of augmentation. Augmentation is a worsening of symptoms with long-term use, and occurs in about one third of WED/RLS patients who take the intermediate-acting dopamine drugs pramipexole and ropinirole (Requip). Both pramipexole and ropinirole are FDA approved for treating WED/RLS and commonly used as first-line therapy.

“Over the long term, the most commonly used treatments for WED/RLS make a bad disease worse,” says Richard P.Allen, PhD, who is first author of the report. Allen is an associate professor in the Department of Neurology at Johns Hopkins University past chair of the WED Foundation’s medical advisory board.

“This study is an important contribution to our knowledge of the treatment of a widespread and very serious medical condition,” said Karla Dzienkowski, executive director of the Willis-Ekbom Disease Foundation, headquartered in Rochester, Minn.

WED/RLS is a disease that produces an overwhelming evening and nighttime urge to move the legs. It wreaks havoc on sleep, disrupts quality of life, and is associated with increased risk of cardiovascular disease. Clinically significant WED/RLS affects from 2 to 3 percent of adults and progressively worsens over time.

While previous studies found that one third of patients became worse over three years of taking ropinirole and pramipexole, it was unclear whether this was caused by the drugs themselves or by natural worsening of symptoms over time.

drugsThe new study used a head-to-head comparison of two drugs at their usual doses for treating WED/RLS: Pramipexole is a drug that mimics dopamine in the brain and is FDA approved for treating WED/RLS. Pregabalin is a pain medication that is neither FDA approved for treating WED/RLS nor commonly used to manage the condition.

In the study, 719 patients received standard doses of either 0.25 or 0.5 mg pramipexole or 300 mg pregabalin. Both drugs were found equally effective in initially relieving WED/RLS symptoms, but after one year of treatment, pregabalin showed a better outcome.

Prior studies found that pramipexole and ropinirole (another dopamine mimic) deceptively provide effective initial treatment followed by an insidious worsening of the disease. This often results in very severe—even painful—symptoms that require a very difficult withdrawal from the medication. “What starts as an evening or nighttime disorder expands to affect the afternoon and even the entire day of some WED/RLS patients, totally disrupting life and the ability to work efficiently,” says Allen.

The new research found worsening of WED/RLS symptoms in only 1–2% of patients taking pregabalin—consistent with the rate of expected natural disease progression. In contrast, a dramatically higher rate of worsening symptoms occurred with pramipexole: 7–9%, mostly during the second half of the 12-month study.

The company producing pregabalin (sold as Lyrica) has not made plans to seek FDA approval for treating WED/RLS. The similar drug gabapentin enacarbil (sold as Horizant) was approved for treatment of WED/RLS in 2011.

Researchers from Pfizer, Massachusetts General Hospital in Boston, the Sleep Research Institute in Madrid, and Tampere University Hospital in Tampere, Finland, also contributed to the study.