BMJ 2013;347:f7615 doi: 10.1136/bmj.f7615 (Published 19 December 2013)
Page 1 of 2
Views & Reviews
VIEWS & REVIEWS FROM THE FRONTLINE
Bad medicine: restless legs syndrome Des Spence general practitioner, Glasgow is steeped in direct payments from pharmaceutical companies and hence conflicts of interest.5
RLS research uses a classic trick: take soft, subjective symptoms that patients report themselves and then pseudoscientifically convert them to an illegitimate numerical rating.6 This can give statistically significant outcomes but with almost no discernible benefit for symptoms, sleep, and quality of life.7 8 There is also a massive unexplainable 40% placebo response in RLS.9 Indeed, rationally, placebos should be the treatment of choice. In addition the epidemiology describes a twofold difference among countries and between sexes.2
All roads lead to neurology, today’s repository for the medically unexplained. Consider the rise of partial epilepsy, tremor, sleep disorders, atypical migraine, complex regional pain syndromes, and paraesthesia, for example. These conditions have limited pathological basis, few objective tests, and are based on symptoms that patients report themselves. The truth is that what we really know about the higher functioning of the brain can be written on the back of a large postage stamp.
Restless legs syndrome (RLS) is deemed a common and serious neurological syndrome that affects 10% of the population,1 with 2-3% considerably affected,2 for which doctors are berated for underdiagnosis and undertreatment.3 The syndrome disturbs sleep and is characterised by restless movement and odd sensations in the legs. It is considered both a movement disorder and a sleep disorder, and various models of causation have been posited. But these symptoms are nebulous and unexplained biologically. In 20 years I have never had a patient present with these as primary symptoms in a consultation. So what I am being told does not reflect what I see. The story of RLS is also a big pharma classic, with its fingerprints all over the research and even involvement in defining diagnostic criteria: “pharmaceutical companies attended the workshop and many of them made very helpful contributions.”4 This cosy group of elite international experts
The biological basis of RLS is implausible, it is not one condition, and the benefit of treatment is marginal. But that hasn’t stopped the drug dealing, involving the usual suspects such as gabapentin derivatives (recently approved by the US Food and Drug Administration),10 strong opioids, and benzodiazepines.1 These psychoactive drugs are difficult to compare with placebo and are associated with dependence and rebound insomnia. Of course the big money is with RLS labelled as a chronic disease so that long term treatments can be peddled,11 despite a derelict research base and short duration of studies.12 RLS is medically unexplained yet the diagnosis is uncritically accepted. We risk overdiagnosis, overtreatment, and iatrogenic harm—classic bad medicine. Competing interests: I have read and understood the BMJ Group policy on declaration of interests and have no relevant interests to declare. Provenance and peer review: Commissioned; not externally peer reviewed. 1 2 3 4
5
National Institute of Neurological Disorders and Stroke. Restless legs syndrome fact sheet. NIH Publication No. 10-4847. Dec 2013. www.ninds.nih.gov/disorders/restless_ legs/detail_restless_legs.htm. Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 2005;165:1286-92. Garcia-Borreguero D, Stillman P, Benes H, Buschmann H, Chaudhuri KR, Gonzalez Rodríguez VM, et al. Algorithms for the diagnosis and treatment of restless legs syndrome in primary care BMC Neurol 2011;11:28. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4:101-19. International Committee of Medical Journal Editors (ICMJE). ICMJE form for disclosure of potential conflicts of interest. www.icmje.org/coi_disclosure.pdf.
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Subscribe: http://www.bmj.com/subscribe
BMJ 2013;347:f7615 doi: 10.1136/bmj.f7615 (Published 19 December 2013)
Page 2 of 2
VIEWS & REVIEWS
6 7 8 9
International Restless Legs Syndrome Study Group. International Restless Legs Syndrome Rating Scale. 2001. www.gsksource.com/gskprm/en/US/images/gsk_content/HORIZANT/ IRLS-rating-scale-form.pdf. Scholz H, Trenkwalder C, Kohnen R, Riemann D, Kriston L, Hornyak M. Dopamine agonists for restless legs syndrome. Cochrane Database Syst Rev 2011;3:CD006009. Quilici S, Abrams KR, Nicolas A, Martin M, Petit C, Lleu PL, et al. Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome. Sleep Med 2008;9:715-26. Trenkwalder C, Garcia-Borreguero D, Montagna P, Lainey E, de Weerd AW, Tidswell P, et al. Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomised, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry 2004;75:92-7.
10 11 12
US Food and Drug Administration (FDA). FDA news release. FDA approves Horizant to treat restless legs syndrome. 7 April 2011. www.fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm250188.htm. Garcia-Borreguero D, Allen R, Kohnen R, Silber M, Winkelman J, Earley C, et al. Summary of recommendations for the long- term treatment of RLS/WED from an IRLSSG task force. http://irlssg.org/summary/. Garcia-Borreguero D, Kohnen R, Silber MH, Winkelman JW, Earley CJ, Högl B, et al. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. Sleep Med 2013;14:675-84.
Cite this as: BMJ 2013;347:f7615 © BMJ Publishing Group Ltd 2013
For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
Page 1 of 2
Views & Reviews
VIEWS & REVIEWS FROM THE FRONTLINE
Bad medicine: restless legs syndrome Des Spence general practitioner, Glasgow is steeped in direct payments from pharmaceutical companies and hence conflicts of interest.5
RLS research uses a classic trick: take soft, subjective symptoms that patients report themselves and then pseudoscientifically convert them to an illegitimate numerical rating.6 This can give statistically significant outcomes but with almost no discernible benefit for symptoms, sleep, and quality of life.7 8 There is also a massive unexplainable 40% placebo response in RLS.9 Indeed, rationally, placebos should be the treatment of choice. In addition the epidemiology describes a twofold difference among countries and between sexes.2
All roads lead to neurology, today’s repository for the medically unexplained. Consider the rise of partial epilepsy, tremor, sleep disorders, atypical migraine, complex regional pain syndromes, and paraesthesia, for example. These conditions have limited pathological basis, few objective tests, and are based on symptoms that patients report themselves. The truth is that what we really know about the higher functioning of the brain can be written on the back of a large postage stamp.
Restless legs syndrome (RLS) is deemed a common and serious neurological syndrome that affects 10% of the population,1 with 2-3% considerably affected,2 for which doctors are berated for underdiagnosis and undertreatment.3 The syndrome disturbs sleep and is characterised by restless movement and odd sensations in the legs. It is considered both a movement disorder and a sleep disorder, and various models of causation have been posited. But these symptoms are nebulous and unexplained biologically. In 20 years I have never had a patient present with these as primary symptoms in a consultation. So what I am being told does not reflect what I see. The story of RLS is also a big pharma classic, with its fingerprints all over the research and even involvement in defining diagnostic criteria: “pharmaceutical companies attended the workshop and many of them made very helpful contributions.”4 This cosy group of elite international experts
The biological basis of RLS is implausible, it is not one condition, and the benefit of treatment is marginal. But that hasn’t stopped the drug dealing, involving the usual suspects such as gabapentin derivatives (recently approved by the US Food and Drug Administration),10 strong opioids, and benzodiazepines.1 These psychoactive drugs are difficult to compare with placebo and are associated with dependence and rebound insomnia. Of course the big money is with RLS labelled as a chronic disease so that long term treatments can be peddled,11 despite a derelict research base and short duration of studies.12 RLS is medically unexplained yet the diagnosis is uncritically accepted. We risk overdiagnosis, overtreatment, and iatrogenic harm—classic bad medicine. Competing interests: I have read and understood the BMJ Group policy on declaration of interests and have no relevant interests to declare. Provenance and peer review: Commissioned; not externally peer reviewed. 1 2 3 4
5
National Institute of Neurological Disorders and Stroke. Restless legs syndrome fact sheet. NIH Publication No. 10-4847. Dec 2013. www.ninds.nih.gov/disorders/restless_ legs/detail_restless_legs.htm. Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 2005;165:1286-92. Garcia-Borreguero D, Stillman P, Benes H, Buschmann H, Chaudhuri KR, Gonzalez Rodríguez VM, et al. Algorithms for the diagnosis and treatment of restless legs syndrome in primary care BMC Neurol 2011;11:28. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4:101-19. International Committee of Medical Journal Editors (ICMJE). ICMJE form for disclosure of potential conflicts of interest. www.icmje.org/coi_disclosure.pdf.
[email protected] For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
BMJ 2013;347:f7615 doi: 10.1136/bmj.f7615 (Published 19 December 2013)
Page 2 of 2
VIEWS & REVIEWS
6 7 8 9
International Restless Legs Syndrome Study Group. International Restless Legs Syndrome Rating Scale. 2001. www.gsksource.com/gskprm/en/US/images/gsk_content/HORIZANT/ IRLS-rating-scale-form.pdf. Scholz H, Trenkwalder C, Kohnen R, Riemann D, Kriston L, Hornyak M. Dopamine agonists for restless legs syndrome. Cochrane Database Syst Rev 2011;3:CD006009. Quilici S, Abrams KR, Nicolas A, Martin M, Petit C, Lleu PL, et al. Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome. Sleep Med 2008;9:715-26. Trenkwalder C, Garcia-Borreguero D, Montagna P, Lainey E, de Weerd AW, Tidswell P, et al. Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomised, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry 2004;75:92-7.
10 11 12
US Food and Drug Administration (FDA). FDA news release. FDA approves Horizant to treat restless legs syndrome. 7 April 2011. www.fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm250188.htm. Garcia-Borreguero D, Allen R, Kohnen R, Silber M, Winkelman J, Earley C, et al. Summary of recommendations for the long- term treatment of RLS/WED from an IRLSSG task force. http://irlssg.org/summary/. Garcia-Borreguero D, Kohnen R, Silber MH, Winkelman JW, Earley CJ, Högl B, et al. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. Sleep Med 2013;14:675-84.
Cite this as: BMJ 2013;347:f7615 © BMJ Publishing Group Ltd 2013
For personal use only: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
