Jan 30 2008

Restless Leg Syndrome

Restless Leg Syndrome (RLS) is a neurological disorder in which there is a sensation of restlessness in the legs. This may be perceived as an unpleasant “drawing” sensation or a feeling of crawling on the skin. These sensations are relieved by moving the legs, and therefore the desire to move increases, ultimately becoming irresistible. The symptoms of RLS are most prominent just before falling asleep and therefore they may delay the onset of sleep, and may also interrupt sleep, and therefore RLS is considered a sleep disorder.

In 2005 Requip (ropinirole) became the first drug approved by the FDA for treatment of RLS. In 2006 this was followed by Mirapex (pramipexole). As we live in the age of the internet and anti-“Big Pharma” conspiracy theories are in vogue, there soon appeared claims that RLS is a fake syndrome, made up by Boehringer Ingelheim and GlaxoSmithKline in order to manufacture a market for their drugs.

Here is an e-mail question I recently received which reflects these common conspiracy claims:

Skepticism uber allas, but that would be an oxymoron. Anyway, I would like to ask you Dr. Novella as a neurologist your opinion of “Restless Leg Syndrome.” My brother who is a physician (dermatologist) told me that his professional colleagues tell him that RLS is a made up myth. That two major pharmaceutical companies have turned their failed sleep meds into a new need and market. We have all seen the massive TV and print media advertising. I have heard you on a past podcast talk about the natural paralysis this is necessary for REM sleep to keep us acting out our dreams. Also, these RLS medications are vasodilators. The effect is relieving the tingling feeling in the legs which is I believe is a result from inactivity. A very American thing.

While I think it is critically important to exercise healthy skepticism toward any self-serving claims, and that includes all marketing (especially within health care), it is equally important to separate fact from fiction and not assume that anything that serves the interest of a corporation must be a lie.

The notion that RLS is a recent fabrication is easy to falsify. I learned about RLS while I was in medical school, and I always have the subjective sense that anything that predated my medical school education is ancient. But to check this out in more detail, I looked up RLS in my Adams and Victor Principles of Neurology, 5th Edition from 1993. Pages 337-338 describe RLS as I did above, and indicate that the more technical name for the disorder is anxietas tibiarum. I also did a Pub Med search on “restless leg syndrome” and the oldest reference dates back to 1960. That would be an awfully long time for GSK to have been planning their deception.

The claim that Mirapex and Requip were failed sleep medications is also demonstrably false. Both of these medications were previously approved by the FDA as treatments for Parkinson’s disease (PD). Both drugs are dopamine agonists – they act in the brain like the neurotransmitter, dopamine, which is lacking in Parkinson’s. One symptom of PD that is present in some patients is akathisia, a restless sensation marked by a desire to move. Akathisia is very similar in character to restless leg syndrome. It was also observed that L-dopa (a precursor to dopamine that is also used to treat for PD) also relieves the symptoms of RLS. It was therefore obvious to consider dopamine agonists, like Mirapex and Requip, for the treatment of RLS and it was a surprise to no one that such drugs worked for the disorder.

Still, there are those who are critical of the current “hype” surrounding RLS and claim that the pharmaceutical companies, aided by a less-than-skeptical media, are pushing the diagnosis. For example, this commentary published in PLoS Medicine writes:

The articles also reinforced the need for more diagnosis. About half reported that the syndrome is underdiagnosed by physicians (“.relatively few doctors know about restless legs. This is the most common disorder your doctor has never heard of” [17]) and underrecognized by patients (“.many people can suffer in silence for years before it is recognized” [18]). One-quarter of articles encouraged patient self-diagnosis and suggested people ask their doctor whether restless legs might explain various problems (including insomnia, daytime fatigue, attention deficit disorder in children, and depression). One-fifth of articles referred readers to the “nonprofit” Restless Legs Foundation for further information; none reported that the foundation is heavily subsidized by GlaxoSmithKline. No article acknowledged the possibility of overdiagnosis (the idea that some people will be diagnosed unnecessarily and take medication they do not really need).

This brings up many interesting and complex issues regarding such diagnoses. Although it is clear that RLS is a real disorder known for over four decades, it is highly plausible and fits well within our understanding of movement disorders and the role of dopamine agonists in treating them – there is always the risk of less-than-rigorous clinicians making the diagnosis based upon vague symptoms. Such “fad” disorders come and go. Also, it is well known that the existence of a diagnosis may drive patients with vague or non-specific symptoms, or with less socially acceptable disorders like depression, to believe that they have the syndrome and to seek treatment.

It is also clear that pharmaceutical companies use advertising to increase public awareness of diseases their drugs treat, and also spend a great deal of money increasing physician awareness of these diagnoses and their drugs. This may also lead to casual overdiagnosis. However, such advertising is not necessarily all bad. Many diseases are grossly underdiagnosed, and raising awareness may actually improve medical care. It is a fallacy to assume that anything that is in the self-interest of a large corporation must be bad.

For example, a recent review article concludes:

Because diagnosis currently relies solely on patient (or caregiver) interview, recognizing the symptoms of RLS and knowing what medications treat this condition–as well as the many that exacerbate it–is important for all health care practitioners.

Knowledge, generally, is a good thing. Optimally, experts will spread the word to their colleagues through lectures, articles, and seminars about how to properly diagnose and treat RLS, to minimize both underdiagnosis and overdiagnosis. Also the media should seek balance in how they report about such disorders and their treatment, although my sense is that the complexity of this situation is above the average journalist and would require a science or health journalist with good sources to get that balance correct. And finally, we have to keep a close eye on pharmaceutical companies to keep them honest. Mostly they make their money by selling effective drugs for real disorders, but they also will put the most advantageous spin on their products. So a dose of healthy skepticism toward their marketing efforts is also a good idea.

But let us not throw the baby out with the bathwater. RLS is real enough and dopamine agonists like Mirapex and Requip are reasonable evidence-based treatments for RLS. And while we need to keep our skeptical radar up, we should not accept knee-jerk conspiracy theories and urban legends about “big pharma.”

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