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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17 responses so far

17 Responses to “Restless Leg Syndrome”

  1. delaneypaon 30 Jan 2008 at 1:24 pm

    Mirapex and Requip are good medicines, but not necessarily the first things to reach for. Try: 1) simply going for a walk before bedtime; 2) checking a ferritin level and corrected iron deficiencies if needed; 3) gabapentin; 4) Sinemet.

    Also, as noted in Wikipedia, RLS actually goes back hundreds of years as a recognized entity: “Earlier studies were done by Thomas Willis (1622-1675) and by Theodor Wittmaack.[19] Another early description of the disease and its symptoms were made by George Miller Beard (1839-1883).[19] In a 1945 publication titled ‘Restless Legs’, Karl-Axel Ekbom described the disease and presented eight cases used for his studies.” I seem to recall in med school about some ancient Greeks writing about the condition.

  2. durnetton 30 Jan 2008 at 1:24 pm

    Thanks for the post. I’ve had restless leg-like symptoms for a couple of decades. My wife has been complaining about my “jimmy leg” since we started dating. My symptoms are periodic and I can’t seem to reproduce them, so I haven’t consulted a physician.

    When the new drugs came on the scene, I was a little skeptical because of some of the same rumors you addressed here. This clears some worries up, but re-enforces my concern that the doctor will simply cave to my self-diagnosis. As a patient, how can I be sure that the physician isn’t simply giving me my own diagnosis back because she is afraid of confrontation with some irrational hypochondriac?

  3. Steven Novellaon 30 Jan 2008 at 2:17 pm

    “Try: 1) simply going for a walk before bedtime; 2) checking a ferritin level and corrected iron deficiencies if needed; 3) gabapentin; 4) Sinemet.”

    Sure, there are other treatments, and I did not imply that these medications need to be first line. To comment on your list, however: 1) This is a good idea, and I certainly recommend it to patients, but most patients have tried this prior to seeking medical advice; 2) Assessing for underlying or predisposing conditions also should be part of a routine evaluation, absolutely; 3) gabapentin can sometimes be helpful, but it is not as effective as dopamine agonists and there is no real reason it should be tried first, except now that it is available as a generic it is cheaper; 4) Sinemet contains L-dopa, which is converted to dopamine, so has the same effect as Mirapex and Requip. This is generally considered to be a second-line choice if the agonists fail.

    Older treatments include clonazepam, which is rarely used now because it is addictive.

  4. Eximious Joneson 30 Jan 2008 at 4:22 pm

    Thank you SO MUCH for addressing this topic. I have suffered from RLS for about ten years (and take gabapentin for it). I had never even heard of RLS until I was diagnosed. There are people who believe in ghosts, acupuncture and Bigfoot, but RLS is what they choose to be skeptical about. Sheesh.

  5. Roy Nileson 30 Jan 2008 at 6:49 pm

    If you can’t cure it, here’s one way to relax and enjoy it.

    http://www.youtube.com/watch?v=Wonk568HiOk

  6. [...] Blogosphere) Tags: big pharma, blog, mirapexin, NeuroLogica, restless leg, scepticism Over at NeuroLogica Blog, Steven has posted about scepticism about Restless Leg Syndrome and the use of dopamine agonists – [...]

  7. yesnokayon 06 Feb 2008 at 5:12 pm

    I think its important to note that this is a typical growth cycle for big pharma drugs. Many were conceived as treatments for other conditions, but through R&D and testing, received approval for other indications.

    This doesn’t mean they are any less effective, or just a ploy to extend the profitability of a compound. Just look at Viagra, it was initially studied for use as a hypertension drug.

  8. LepleyDOon 16 Feb 2008 at 12:03 am

    “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.”

    What you call raising awareness, I would call disease mongering. I would say this out of concern for healthcare costs in general, however, and not a prioiri anti-pharm ideology. Your post seems to suggest that criticism of RLS hype can only arise from knee jerk industry skepticism.

    I think as a neurologist, your vantage point of RLS is different than what I see in primary care. You see more cases of RLS, and more severe cases causing significant disability. But, by far, the bigger public health problem is rising healthcare cost, and people’s inability to afford health insurance. RLS hype, which you acknowledge can lead to overdiagnosis, will escalate cost, and reduce people’s access to health insurance. This is the harm.

    I’ve never seen a seminar or educational program on RLS offered in my area that wasn’t industry sponsored.

    Also, RLS probably exists on a continuim, with medications reserved for those on the moderate to severe end of the spectrum. However, now the typical patient comes in specifically requesting the medication, and doctors have to work backwards from there. This leads to a tendency to overprescribe, because as a business there is a “customer is always right” axiom that exists in doctors offices.

    If anything, the RLS hype also hurts Parkison’s patients, because the increase cost has led some insurers to make these drugs “prior authotization only” which makes it harder for PD patients to obtain the medications.

  9. Steven Novellaon 16 Feb 2008 at 9:24 am

    LepleyDO,

    I acknowledged that promoting a specific treatment for a specific disease can lead to overdiagnosis and over prescribing. My point was that this is not necessarily the case. Also, evidence suggests that underprescribing is as common as overprescribing.

    I agree with your point about healthcare costs – but let’s call this what it is – rationing health care. You are essentially saying that increasing awareness of a disease and treatment leads to people being treated and this raises health care costs – which is true whether or not the treatment is appropriate. We both agree that overprescribing is bad, but how do you define this. If medication for moderate RLS improves someones quality of life, is that worth it?

    I also think you are underestimating the consequences of RLS in many patients, which is sleep deprivation. This has a host of negative health consequences and may even increase the ultimate cost of health care.

    The solution to overdiagnosis is not censorship but physician education.

    On your final point, I have not found this causes a problem in getting these medication to PD patients. At worst it creates more work for my office staff who have to submit the prior auth. But I blame this on the insurance companies – not an evidence-based extension of the indication for these meds.

  10. LepleyDOon 16 Feb 2008 at 11:28 am

    I disagree. I’m not suggesting we ration healthcare, I’m suggesting we should curb the consumerism and restrict DTC advertising. This is not necessarily censorship, and many industrialized countries do this which share our same free speech values.

    I agree I probably do underestimate the negative consequences of RLS, in primary care my knowledge is superficial on a range of diseases. But I do think you underestimate how difficult it can be to find independent sources of physician education outside of academic institutions. Pretty much all the CME lectures I come across are industry sponsored. I think it’s like this in many smaller communities.

    Independent education is costly for the independent physician. Industry sponsored seminars tend to be free for me, the bill being footed by the drug companies. Compare an analysis of various medications on Medscape, a “free” education service (heavy on pharm ads), to one from “The Medical Letter”, a nonprofit, pharm-free, subscription service, and subtle but real differences are apparent.

    I also think you underestimate the strain that prior auth’s can put on a small independent practice trying to minimize overhead. But I agree that this is more of an insurance problem than the pharm industry.

    I agree that these medicines help RLS. I just think the way they are marketed directly to patients, and the way the industry educates physicians, is what is harmful.

  11. LepleyDOon 16 Feb 2008 at 11:33 am

    “The Medical Letter” is far more discerning and credible about the risks and benefits of various medications than Medscape, in my opinion. The cost makes it less accessible. Which is the point I was trying to make above.

  12. [...] inconveniencing their buddies in “Big Pharma.” (Carrey also throws in the myth that restless leg syndrome is a made up diagnosis by Big Pharma – so I guess he only has to care about diseases that touch him [...]

  13. [...] I cover dubious medical topics on this blog in order to expose them, but occasionally I cover diseases or disorders that are genuine but may seem questionable. That is just one more of the negative [...]

  14. Privicon 23 May 2011 at 5:22 pm

    I tried so many things to stop my legs from shaking, and I only found this privic spray that calms my legs. You can check their website, http://www.privic.com. Hope it can help you too!

  15. clinicalgpson 21 Dec 2011 at 6:01 pm

    There are a number of clinical research trials around the country which are focused on developing new treatments for restless leg syndrome. Regardless of what some people may believe, there are people out there who are affected by this condition. For a full list of restless leg clinical research trials check http://www.clinicaltrialsgps.com/clinical-trials-indications/restless-leg-syndrome/.

  16. AchieveAlabamaon 09 Jan 2013 at 5:17 pm

    Hey, I really like the post that you have provided here. I know that this can be a complex condition, and sometimes people can live for years without knowing the cause of these sensations. If you are looking for more resources on RLS clinical trials, then you should also go check out: http://www.achieveclinical.com/clinical-trials/restless-leg-syndrome/ This page has some valuable information, which you should look over carefully if you are considering taking part in a trial.

  17. Avail DeLandon 18 Feb 2013 at 10:24 pm

    I agree with what is being said on the subject of RLS clinical studies. I know that there is some confusion that still surrounds this particular condition, and many people just don’t understand what it can be like to feel those sensations in their legs on a constant basis. For that reason, we have added an educational video on restless leg syndrome, which can be viewed at: http://www.availclinical.com/clinical-trials/restless-leg-syndrome/

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