After a speedy rise as one of the nation’s oddest-sounding designer disorders, restless legs syndrome may have run its course.
In 2005, the federal Food and Drug Administration approved the first medication targeting the twitching condition, propelling the problem to household-name status and launching a multimillion-dollar consumer advertising campaign by manufacturer GlaxoSmithKline.
Television ads touting ropinirole hydrochloride, a drug originally used to treat Parkinson’s disease, sent jittery patients to doctors’ offices to demand the brand name medication called Requip.
“People would call me and say ‘Did you see the commercial for restless leg?’’’ recalled Gloria Konrad, 58, of Loudon, Tenn., who says she’s suffered from the disorder for a decade. “My husband never believed me until all these people started saying they had it.”
Within a year, sales of Requip had doubled, climbing from $165 million in 2005 to nearly $330 million in 2006. By last year, 4.4 million prescriptions were written for the drug, with sales of nearly $491 million, according to IMS health, an industry information agency.
But a new FDA decision could reverse the trajectory of the ailment characterized by what Konrad describes as “creepy crawly” nighttime sensations that force her and other sufferers to move their legs, often interrupting sleep.
Last week, the drug agency approved the first generic versions of ropinirole tablets for four manufacturers. The move is likely to send Requip sales and advertising plummeting, industry experts predicted.
At least one sleep disorder specialist expects the focus on restless legs syndrome to fade as rapidly as the Requip television commercials — which have already been pulled from the airwaves.
“Restless legs syndrome is a great example of a suddenly out-of-the-blue disease,” said Dr. Christopher J. Earley, an associate professor of neurology at Johns Hopkins University in Baltimore who treats the disorder.
Advertising created an overheated demand for diagnosis among consumers, while easy-to-dispense drug samples provided a convenient response for busy doctors, he said.
"I would anticipate there would be something of a fall-off," Earley said, adding: “I think we need to take the kettle off the stove and let it cool down a bit."
That prediction alarms patient advocates who have welcomed public attention — and drug industry funding — for the little-known disorder described for centuries in literature and first defined in 1945.
“I think there certainly has been awareness about restless legs syndrome since the approval of ropinirole in 2005,” said Georgianna Bell, executive director of the Restless Legs Syndrome Foundation based in Rochester, Minn.
“RLS was seen as a common disorder, under-diagnosed and unrecognized. I think that may still be true to some extent," she added.
Some call it 'disease mongering'
But the possible change heartens critics who cite restless legs syndrome as a prime example of “disease mongering,” in which promoters such as drug companies deliberately enlarge the market for a product by convincing people that they’re sick and need treatment.
“You may have something that’s a normal condition,” said Dr. Lisa M. Schwartz, associate professor of medicine and community and family medicine at Dartmouth Medical School in Hanover, N.H. “It makes you wonder whether there’s a disease to be treated.”
Schwartz and her husband, Dr. Steven Woloshin, also at Dartmouth, say that drug company promotions, combined with uncritical media reporting, have exaggerated the prevalence of restless legs syndrome and led to over-diagnosis and over-treatment with powerful brain-altering drugs.
If the generic switch leads to fewer ads, that should decrease patient demand for diagnosis and treatment, leaving only the most serious sufferers to weigh the benefits of the drugs against the risks of potentially severe side effects.
Whether the ads decline depends largely on the makers of Mirapex, the second-leading drug approved to treat restless legs syndrome, said Schwartz.
“If it ends up that they pull back, the market might go down,” Schwartz said.
Representatives for Boehringer-Ingelheim, the makers of Mirapex, the brand name for pramipexole, declined to discuss whether their advertising strategy would change.
Ads for Requip are off the air now, according to a spokeswoman for GlaxoSmithKline, who said she couldn’t speculate about future plans. In any event, the company anticipates sales of Requip will fall as generic drugs become available.
“It’s usually a pretty sharp drop,” said Mary Anne Rhyne, the Glaxo spokeswoman.
Prevalence estimates exaggerated
Exactly who suffers from restless legs syndrome and how they should be treated has been a subject of considerable debate since GlaxoSmithKline began raising the profile of the disorder. Estimates of the prevalence of restless legs syndrome range from about 1 percent to as high as 12 percent of the population, which would be about 36 million Americans.
Best evidence suggests that about 5 percent of the population may have the condition, with about 2 percent to 3 percent of cases being moderate to severe, estimated Earley and Dr. Phyllis Zee, a professor and sleep expert at Northwestern University Medical School in Chicago. Woloshin said validated studies put the prevalence at about 3 percent.
“How many people really need treatment? Probably 1.5 percent to 2 percent of the population,” said Earley. “It still represents a significant number of people.”
Earley and Zee reject the suggestion that restless legs syndrome is an imaginary condition. Zee noted that researchers in Germany and Iceland recently detected a genetic link to the problem, though she acknowledged that it’s not clear what the link might mean. No one really knows what causes restless legs syndrome, only that it exists, the scientists said.
“It’s not a made-up disorder,” Zee said. “It’s been recognized for many years, but I don’t think we really understood the impact of the quality of life on patients.”
Both Zee and Earley acknowledged that they have received payment for providing talks or consultations for GlaxoSmithKline and for Boehringer-Ingelheim. Schwartz and Woloshin said they have no such conflicts.
Requip and Mirapex were used for years off-label to treat restless legs syndrome, before acquiring FDA approval in 2005 and 2006, respectively. Before that, antidepressants or opiates were commonly used to treat the disorder if methods such as reducing caffeine and altering diet, exercise and sleep habits didn’t work.
Though drugmakers portrayed their products as a sure-fire cure for symptoms, the reality isn’t so certain. People who took the drugs, known as nonergot dopamine agonists, were 36 percent more likely to respond to the treatment than people who took placebos, according to an analysis of 14 randomized controlled trials presented this week in the May/June issue of the Annals of Family Medicine.
But the range varied considerably in the trials, none of which lasted more than 12 weeks. In one trial, for instance, 17 of 32 people, or 53 percent, who took ropinirole responded to the drug, compared to 17 of 33 people, or 52 percent, who took sugar pills. In another study, the difference was 61 percent versus 52 percent.
“There’s such a huge placebo effect,” Schwarz said.
Side effect: Falling asleep while driving
At the same time, the side effects of the drugs can be considerable. Patients taking the drugs were about 35 percent more likely to withdraw from trials because of problems than those taking the placebo, the study showed. The biggest problems included debilitating nausea, dizziness and falling asleep during daily activities.
Other studies have shown the drugs can cause compulsions such as gambling or sexual promiscuity.
The generic drugs approved by the FDA will carry the same warning applied to Requip. It cautions that some patients have reported falling asleep with no warning, even while driving.
Even when the drugs do work, patients face problems of increased tolerance, which can progress into a condition called augmentation, in which the drug actually increases the symptoms of restless legs syndrome.
For many patients, however, the medications provide significant relief from a debilitating condition, said Zee.
“In my opinion, in general, the benefits outweigh the risks,” she said. “Now, you have to individualize. If they’re so bad with the disease, most of these side effects won’t matter.”
Patients such as Lynne Kaiser, 44, of Dallas, Texas, know the problems too well. She says she’s had restless legs syndrome since she was born and tried every possible treatment for the condition that feels like dozens of tiny, sharp needles repeatedly puncturing her limbs.
“It’s like having somebody poke you in the front of the head all the time, saying: ‘You have legs, you have legs, you have legs. Did you know you have legs?’” said Kaiser. “You would do almost anything to get sleep and have relief. You just start to lose your life.”
Her disease is so bad that the drugs no longer work. That was the case, too, for Gloria Konrad. Both women say they’re in the minority of severe cases that require individualized treatment that goes beyond a simple pill. Konrad, for instance, swears by vegan wellness oils that she says have relieved pain and helped her sleep.
‘People are not lemmings’
Debates about over-diagnosis get in the way of helping people like Kaiser and Konrad, said Bell, the director of the Restless Legs Syndrome Foundation.
“People are not lemmings to be led to the edge of the cliff and dropped off,” she said. “You’re making it sound like Glaxo and BI are telling people what to do. And that’s simply not true.”
Bell said she’s “a little tired” of charges that the disorder is the product of disease mongering. She acknowledges that about a third of the agency’s $1.2 million budget comes from corporate sponsorships from the two large drugmakers, but says the foundation is working to expand its funding base.
"We are here, we were here before GlaxoSmithKline and Boehringer-Ingelheim and we will be here after them," she said.
Bell believes the generic drugs will be a boon for patients, providing wider access at lower cost.
Still, there’s no denying that a drop in advertising could have an effect on the popularity of the drug for what was lampooned on “Seinfeld” as “jimmy legs.”
“This is going to be an interesting transition to follow. Folks may not be asking their docs for the once-highly-advertised drug to treat the leg twitch they were led to believe was a disease worthy of drug treatment,” said Gary Schwitzer, an associate professor in the University of Minnesota School of Journalism and Mass Communication, in an e-mail. Schwitzer studies direct-to-consumer advertising.
Doctors may not be inclined to prescribe the drug if the supply of brand-name samples disappears. And the generics won’t come with samples, Schwitzer added.
Whatever happens with restless legs syndrome, it won’t spell the end of disease mongering, he said.
“Does it really matter whether prescriptions drop off for restless legs syndrome drugs?” he said. “The void will be filled with new drugs for baldness, wrinkles, dandruff, toenail fungus and other dread diseases.”