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Restless Legs Syndrome David Atkins 2-28-08 PAS 645-646 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 Is RLS even REAL? YES. HISTORY of RLS • Phenomenon was described as early as 17th 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. Epidemiology Roughly 10% prevalence in the general population of U.S. and Western Europe. Significantly lower rates in African Americans. Higher incidence in women? Etiology • IDIOPATHIC • Genetic Linkage: 3 separate loci have been identified, none solely responsible. • Most research is aimed at dopamine and/or iron pathologies. Two Forms of RLS: • Primary (idiopathic): Secondary RLS: • Early onset: usually manifests before 45 • Later age of onset • Familial: >60% have at least 1 primary family member with RLS. • No family history of RLS • More gradual progression of Sx over time. • Rapid progression of Sx. 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 Diagnosing RLS 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. ALWAYS try non-pharm. Tx Behavioral/Lifestyle modification: Practice good sleep hygeine Regular moderate exercise, but at the right times Other anecdotal methods st 1 Avoid Sx aggravators: caffeine nicotine alcohol diphenhydramine TCA's SSRI's neuroleptics 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 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 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 Pharmacologic Tx As a clinician... • • • • • • Diagnose RLS using essential criteria. -Consider +FH, underlying cause, and assess iron status Educate patient and attempt nonpharmacologic 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. 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.