1. Restless Legs Syndrome David Atkins 2-28-08 PAS 645-646

2. What is RLS ? Restless Legs Syndrome (RLS) is a sensorimotor movement disorder. Characterized by: – an uncontrollable urge to move the legs – symptoms typically begin in the evening or at bedtime, preventing the sufferer from falling asleep

3. Is RLS even REAL? YES.

4. HISTORY of RLS Phenomenon was described as early as 17 th century by Thomas Willis. Closely observed in 1945 by Karl-Axel Ekbom who coined the term "Restless legs" (formerly called "Ekbom-syndrome"). Diagnostic criteria outlined by International RLS Study Group (IRLSSG) in 1995. Revised in 2003.

5. Epidemiology Roughly 10% prevalence in the general population of U.S. and Western Europe. Significantly lower rates in African Americans. Higher incidence in women?

6. Etiology IDIOPATHIC Genetic Linkage: 3 separate loci have been identified, none solely responsible. Most research is aimed at dopamine and/or iron pathologies.

7. Two Forms of RLS: Primary (idiopathic): Early onset: usually manifests before 45 Familial: >60% have at least 1 primary family member with RLS. More gradual progression of Sx over time. Secondary RLS: Later age of onset No family history of RLS Rapid progression of Sx.

8. Secondary RLS Usually related to disorders that result in iron deficiency. Most common underlying causes of secondary RLS: –Pregnancy –Anemia –End-stage renal disease –ADHD

9. Diagnosing RLS

10. Treating RLS There is no cure, Tx is symptomatic only Pharmacologic vs. Non-pharmicologic Many treatments out there, but all lack sufficient research…studies are ongoing.

11. ALWAYS try non-pharm. Tx 1 st Behavioral/Lifestyle modification: Practice good sleep hygeine Regular moderate exercise, but at the right times Other anecdotal methods Avoid Sx aggravators: caffeine nicotine alcohol diphenhydramine TCA's SSRI's neuroleptics

12. NON-Pharmacologic Tx: IRON Iron supplementation: 50-65mg tid (+Vit C) IV: sodium ferric gluconate or iron sucrose Only beneficial if serum ferritin <50μg/L

13. Pharmocologic Tx DA-agonists are drugs of choice: –Levadopa (d.o.c. for intermittent RLS) –Ropinirole (Requip ® ) FDA approved for RLS in May, 2005. –Pramipexole (Mirapex ® ) FDA approved for RLS in November, 2006. Both indicated for moderate-severe RLS. No studies (yet) comparing ropinirole to pramipexole

14. Other Rx options: Opioids Benzodiazepines Anti-convulsants BZDP's: very popular before DA-agonists became first line, with good results. Both BZDP's and Opioids have low dependence and abuse potential when used for RLS

15. Pharmacologic Tx

16. As a clinician... Diagnose RLS using essential criteria. - Consider +FH, underlying cause, and assess iron status Educate patient and attempt non- pharmacologic therapies (d/c Sx aggravators) If non-pharm Tx fails, Rx a dopaminergic. If dopaminergics fail, try one of the "others". May use combo of dopaminergic + "other". Remember: all pts experience RLS and respond to Tx differently.

18. References: Essential Dx table: Patrick L. Restless Legs Syndrome: Pathophysiology and the Role of Iron and Folate. Altern Med Rev. 2007 Jun;12(2):101-12. Common Pharmacologic drugs: Hening WA. Current guidelines and standards of practice for restless legs syndrome. Am J Med. 2007 Jan;120 (1 Suppl 1):S22-7. Tx Algorithm: Ryan M, Slevin JT. Restless legs syndrome. Am J Health Syst Pharm. 2006 Sep;63(17):1599-612.