Restless legs syndrome: Diagnostic time-savers, Tx tips

,; ,

Applied Evidence

Restless legs syndrome: Diagnostic time-savers, Tx tips

J Fam Pract. 2009 August;58(8):415-423

PDF Download

References

1. Karroum E, Konofal E, Arnulf I. Restless-legs syndrome. Rev Neurol. 2008;164:701-721.

2. Vergne-Salle P, Coyral D, Dufauret K, et al. Is restless legs syndrome underrecognized? Current management. Joint Bone Spine. 2006;73:369-373.

3. Fulda S, Wetter TC. Dopamine agonists for the treatment of restless legs syndrome. Expert Opin Pharmacother. 2005;6:2655-2666.

4. Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med. 2005;165:1286-1292.

5. Conti C, de Oliveira MM, Andriolo RB, et al. Levodopa for idiopathic restless legs syndrome: evidence-based review. Mov Disord. 2007;22:1943-1951.

6. Restless Legs Syndrome Foundation. RLS Medical Bulletin. 2005. Available at: http://www.irlssg.org/RLSMB2005pf.pdf. Accessed July 9, 2009.

7. Ryan M, Slevin J. Restless legs syndrome. Am J Health Syst Pharm. 2006;63:1599-1612.

8. Oertel W, Trenkwalder C, Zucconi M, et al. State of the art in restless legs syndrome therapy: practice recommendations for treating restless legs syndrome. Mov Disord. 2007;22(suppl 18):S466-S475.

9. Thorpy M. New paradigms in the treatment of restless legs syndrome. Neurology. 2005;64(12 suppl 3):S28-S33.

10. Winkelman J. A better future for patients with restless legs syndrome. Am J Med. 2007;120(1 suppl 1):S28-S29.

11. Chahine L, Chemali Z. Restless legs syndrome: a review. CNS Spectr. 2006;11:511-520.

12. Johnson E. Omnibus Sleep in America poll. National Sleep Foundation. 1998.-

13. Rothdach AJ, Trenkwalder C, Haberstock J, et al. Prevalence and risk factors of RLS in an elderly population: the MEMO study. Neurology. 2000;54:1064-1068.

14. Garcia-Borreguero D. Time to REST: epidemiology and burden. Eur J Neurol. 2006;13(suppl 3):S15-S20.

15. Schapira A. RLS patients: who are they? Eur J Neurol. 2006;13(suppl 3):S2-S7.

16. Benes H, Walters AS, Allen RP, et al. Definition of restless legs syndrome, how to diagnose it, and how to differentiate it from RLS mimics. Mov Disord. 2007;22(suppl 18):S401-S408.

17. Hening W, Allen R, Tenzer P, et al. Restless legs syndrome: demographics, presentation and differential diagnosis. Geriatrics. 2007;62:26-29.

18. O’Keefe ST, Gavin K, Lavan JN. Iron status and restless legs in the elderly. Age Ageing. 1994;23:200-203.

19. Sun ER, Chen CA, Ho G, et al. Iron and the restless legs syndrome. Sleep. 1998;21:371-377.

20. Akpinar S. Restless legs syndrome treatment with dopaminergic drugs. Clin Neuropharmacol. 1987;10:69-79.

21. Becker P, Jamieson A, Brown D. Dopaminergic agents in restless legs syndrome and periodic limb movements of sleep: response and complications of extended treatment in 49 cases. Sleep. 1993;16:713-716.

22. Von Scheele C, Kempi V. Long-term effect of dopaminergic drugs in restless legs. A 2 year follow-up. Arch Neurol. 1990;47:1223-1224.

23. Bertoni JM, Arlette JP, Fernandez HH, et al. Epidemiologic association of Parkinson’s disease and melanoma. Mov Disord. 2006;21(suppl 15):S610.-

24. Fiala K, Whetteckey J, Manyam B. Malignant melanoma and levodopa in Parkinson’s disease: causality or coincidence? Parkinsonism Relat Disord. 2003;9:321-327.

25. Montagna P. The treatment of restless legs syndrome. Neurol Sci. 2007;28(suppl 1):S61-S66.

26. Kushida C. Clinical presentation, diagnosis and quality of life issues in restless legs syndrome. Am J Med. 2007;120(1 suppl 1):S4-S12.

27. Baker W, White C, Coleman C. Effect of nonergot dopamine agonists on symptoms of restless legs syndrome. Ann Fam Med. 2008;6:253-262.

28. Fulda S, Wetter T. Emerging drugs for restless legs syndrome. Expert Opin Emerg Drugs. 2005;10:527-552.

29. Walters A, Wagner M, Hening W, et al. Successful treatment of idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep. 1993;16:327-332.

30. Walters A, Winkelman J, Trenkwalder C, et al. Long term follow-up on restless legs syndrome patients treated with opioids. Mov Disord. 2001;16:1105-1109.

31. Boghen D, Lamothe L, Elie R. The treatment of restless legs syndrome with clonazepam: a prospective controlled trial. Can J Neurol Sci. 1986;13:245-247.

32. Peled R, Lavie P. Double-blind evaluation of clonazepam on periodic leg movements in sleep. J Neurol Neurosurg Psychiatry. 1987;50:1679-1681.

33. Ferni-Strambi L. RLS-like symptoms: differential diagnosis by history and clinical assessment. Sleep Med. 2007;8(suppl 2):S3-S6.

Review the need for iron replacement

The role that low levels of iron play in RLS is not entirely clear. One study found the median ferritin level in patients with RLS symptoms to be 33 mcg/L, compared with 59 mcg/L in those without symptoms.¹⁸ Another study showed patients with ferritin levels less than 50 mcg/L to have more severe RLS symptoms than those with levels greater than 50 mcg/L.¹⁹ Both iron and dopamine have been shown to have circadian rhythms similar to RLS, with their nadir correlating with the time of maximum severity of RLS symptoms. (Low levels of iron may be associated with either idiopathic or secondary RLS.)

FAST TRACK

Any patient with a plasma ferritin concentration <50 mcg/L and RLS symptoms should be started on iron replacement therapy.

Consensus guidelines recommend against initiating iron replacement therapy without checking levels, as this could lead to iron overload.⁶ Any patient with a plasma ferritin concentration <50 mcg/L and RLS symptoms should be started on iron replacement therapy. The recommended dose of iron is 325 mg ferrous sulfate, taken with 300 mg vitamin C, 3 times a day. Vitamin C allows for better absorption of the iron.⁸

Monitor ferritin levels at 6-week intervals until they exceed 50 mcg/L, then check iron concentrations every few months. Iron replacement therapy can be decreased or discontinued, provided the ferritin remains at this level.¹⁷

Try these strategies for symptom relief

The goal in treating RLS is to decrease the severity and frequency of symptoms, leading to an improvement in sleep quality, a decrease in daytime somnolence, and an overall improvement in quality of life. Treatment guidelines, supported by the IRLSSG and the Medical Advisory Board of the Restless Legs Syndrome Foundation, are based on symptom frequency and severity—whether they are intermittent, daily, or refractory.^3,9,17

The algorithm ( FIGURE ) provides recommendations for starting and escalating pharmacologic therapy. Nonpharmacologic treatments have not been studied in systematic trials; however, recommendations for their use are based on expert opinion, case series, or anecdotal reports. In patients who do not have severe symptoms, it makes sense to try simpler strategies first.

Review medications and diet. Many medications have been associated with RLS, either as a secondary cause or suspected of exacerbating symptoms. These include dopamine antagonists (neuroleptics, antiemetics); antidepressants, primarily tricyclics and selective serotonin reuptake inhibitors, lithium, and antipsychotics; antihistamines, including diphenhydramine and other over-the-counter cold and allergy remedies; calcium channel blockers; and diuretics.^6,8,17

FAST TRACK

If no substitute can be found for a medication associated with RLS symptoms, consider changing the dosing schedule to earlier in the day.

If a patient troubled by symptoms of RLS is taking any of these agents, consider changing the medication. If no suitable substitute is available, it may help to change the dosing schedule to earlier in the day—ideally no later than 3 PM.^8,17 Advise patients, too, to avoid caffeine, tobacco, and alcohol, as well as any other food or beverage known to contain stimulants.

Encourage activity. Discuss the importance of exercise in the management of RLS symptoms. Encourage patients to routinely engage in physical activity and to pursue mentally stimulating activities such as reading, puzzles, or games.

Stress good sleep hygiene. Urge patients to follow a consistent sleep schedule, going to sleep and awakening at the same time each day; to use the bed only for rest or intimacy and avoid reading or watching TV in bed; and to establish a relaxing bedtime routine. Some patients have found that hot or cold baths before bed help to relieve symptoms; others report that massaging their legs or stretching leads to an improvement in symptoms.^7,9,17

FIGURE
RLS: A treatment algorithm^2,7,9,20

FESO₄, ferrous sulfate; RLS, restless legs syndrome.

Pharmacologic options: Selecting the right one

In addition to iron replacement, there are 5 major types of RLS treatment:

dopaminergic agents,
dopamine agonists
anticonvulsants,
opioids,
benzodiazepines.

Carbidopa/levodopa for intermittent symptoms

Most patients with RLS have a positive response to treatment with dopaminergic agents, at least initially, and for many years carbidopa/levodopa was the usual therapy for RLS. It remains a first-line treatment for patients with intermittent symptoms.

FAST TRACK

Carbidopa/levodopa is a good choice for patients with intermittent symptoms because it can be taken on an as-needed basis.

Early studies consistently showed that 70% to 80% of RLS patients treated with carbidopa/levodopa had a significant improvement in symptoms.^20-22 But the studies were small, did not always include a placebo arm, and most were crossover trials, making it impossible to do a statistical comparison.⁵