12 Million Can't Sleep, Can't Sit With Restless Legs Syndrome

When Richard Jefferson was 7 years old, his legs twitched so uncomfortably his parents would put them in ice packs to ease the creepy-crawly pain.

As he got older, the symptoms got worse: When in bed his legs flailed and woke him from sleep, and he couldn't sit through a movie or dinner at a restaurant.

"I used to beat them because I would rather have pain than restless legs," said Jefferson, now 62, of Rochester, N.Y. Once the retired assemblyman became so distressed he checked into the emergency room and received morphine. "The minute you sit down, it starts all over again. I've had to plan my life around it."

Jefferson -- like an estimated 12 million Americans -- suffers from restless legs syndrome, a neurological disorder characterized by an uncontrollable urge to move when at rest. Many more people go undiagnosed or misdiagnosed, according to the Restless Legs Foundation.

Sensations are often described as burning, creeping, tugging, or like insects crawling inside the legs. They can range from irritating to painful. Patients complain that they cannot sleep, and if the condition is left untreated, it can cause exhaustion and lead to social isolation.

For decades, Jefferson has searched to find the right medicine, and when doctors prescribed Requip (ropinirole) -- the drug most commonly prescribed for RLS -- he found relief. But only for six months. Then the treatment backfired.

In a recent article in the Journal of General Internal Medicine, neurologists at the University of Rochester Medical Center warned that drugs like Requip and a similar drug Mirapex (pramipexole) can actually make the symptoms worse.

These drugs -- so-called dopamine agonists -- have an "augmentation" effect -- that is, they can heighten the symptoms they are ostensibly treating. They act on dopamine receptors in the brain that help coordinate smooth movement.

These newer drugs, which are safer and have fewer side effects, have replaced dopamine drugs like Levodopa and Sinemet for treatment of RLS. The older drugs can cause intense movement, low blood pressure and nausea, and cause problems when used long-term.

Other drugs used for RLS, like narcotic painkillers and benzodiazepines, produce the opposite effect of the dopamine agonists. With long-term use, patients require higher doses, which produce side effects, including addiction.

Requip has historically been used to treat Parkinson's disease and Tourette's syndrome. But in the past year, the drug has been heavily marketed for treatment of RLS in direct-to-consumer advertising. One prominent ad for Requip aired during the Super Bowl last year.

"It's impossible to tell the whole story in a TV spot just a few seconds long," said Dr. Irene Richard, a movement disorder neurologist at 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."

Rochester neurologists recommend doctors rotate patients through a variety of drugs to avoid augmentation.

"We think of the dopamine medicines as benign and controlled substances like Valium as addictive," Richard said. "But you have to be careful not to make the situation worse, and what is heralded as benign is not."

Requip is manufactured by GlaxoSmithKline, which saw a 34 percent increase in sales to about $78 million following its U.S. marketing launch for treatment of RLS, according to the company's 2005 annual review.

GlaxoSmithKline is aware of augmentation, according to Holly Russell, the director of product communication, and includes it in the Requip safety literature. She said the ads had increased awareness about RLS.

"Patients have told us their doctors did not appreciate their condition," Russell said. "They have suffered alone and blamed themselves for their symptoms."

Some physicians mistakenly attribute the RLS symptoms to nervousness, insomnia, stress, arthritis, muscle cramps or aging.

RLS occurs in both sexes, although the incidence may be slightly higher in women. The syndrome can begin in childhood, but it mostly hits in middle age or later. The severity of the disorder increases with age.

More than 80 percent of sufferers experience periodic limb movement disorder, which is characterized by involuntary leg twitching or jerking movements during sleep that typically occur every 10 to 60 seconds.

Jim Dunlap of Harvard, Mass., has experienced periodic limb movement disorder all his life, waking five or six times each night. The 87-year-old refuses treatment for his restless legs and spends sleepless hours working on his computer or walking around the house. A bad experience with benzodiazepines has put him off medications.

"I was so disoriented that I couldn't find my way back to bed from the bathroom," he said.

Richard Jefferson tried everything -- from quinine water to painkillers -- for his restless legs. Doctors eventually prescribed Requip, but it worked for only six to eight months.

When the doctors upped the dosage, it backfired. While being asked to lie still for an evaluation at Johns Hopkins medical center, "I was climbing the walls," said Jefferson.

Today Jefferson is being successfully treated with methadone, but doctors are not sure how long that will last.

"There's nothing left for me to try," said Jefferson, whose mother, two sisters and daughter also suffer from the condition.

Researchers are investigating the genetic component of the disease and hope to find soon the biological markers that will elevate the syndrome to a disease, according to Georgianna Bell, executive director of the Restless Legs Foundation.

Bell believes dopamine agonist drugs have provided relief for many patients, and that the well-documented augmentation effects do not occur in all cases.

"Yes, it's a problem, though it is not clear how common it is," Richard said. "The jury is still out, but it is an area of active interest."

Using drugs in different combinations seems to provide the best results for most people with RLS, she said. "What works for one may not work for another. And what works for you now may not work six months from now."

According to the Restless Legs Foundation, which has provided educational information on RLS for 15 years, many people with less severe symptoms find relief in quality of life changes, like giving up alcohol, caffeine at night and even letting up on exercise, which can trigger those leg sensations.

Still, many patients have had success with these new drugs. Nelly Cardinale of Webster, N.Y., who was diagnosed when she was 68, tried self-help methods until she was diagnosed with cancer in 2000 and underwent radiation and chemotherapy.

"It got to the point that I couldn't lie down and in the middle of the night -- my legs were jumping and I couldn't read or watch TV," Cardinale said. "I got so tired I would walk around crying. For a year, I couldn't get the rest I needed."

She is now being treated with Mirapex, a dopamine agonist like Requip that has cured -- at least temporarily -- all her symptoms.

"For the first time, I slept," Cardinale said. "I cried on the phone to the doctor, 'Thank you so much.' It's a miracle."