1. www.wemove.org RLS Slide Library Version 1.0 - All Contents Copyright © WE MOVE 2001 Restless Legs Syndrome: Classification, Diagnosis and Approaches to Treatment Part 3 of 3

2. RLS Treatment Goals Eliminate or minimize associated symptoms Reduce EDS Improve overall quality of life Improve activities of daily living www.wemove.org

3. Overall Treatments Nonpharmacologic Pharmacological www.wemove.org

4. Possible Underlying Disorders Anemia Folic acid deficiency End-stage renal disease www.wemove.org

5. Potential Aggravators of RLS Tobacco products Alcohol Caffeine Certain medications Sleep deprivation www.wemove.org

6. Potentially Beneficial Strategies Maintaining a regular sleep regimen Sleeping late in the circadian cycle Undertaking regular, moderate exercise www.wemove.org

7. Additional Approaches Tasks that engage the mind during sedentary periods Bedtime massages Hot baths Cold packs or hot compresses www.wemove.org

8. Scope of RLS Treatment Established therapies are pharmacologic No known cure Therapy directed at symptomatic relief and improved ADLs and QOL www.wemove.org

9. Start Treatment

10. Initiation of Drug Therapy Review medical history and current drug regimen Use single drug, when possible, for comorbidities PRN meds for episodic RLS Use minimal effective dose Treatment during early evening hours www.wemove.org

11. Dopaminergic Agents: First-line RLS Therapies Dopamine agonists (DAs) Dopamine precursors (levodopa) www.wemove.org

12. Dopamine Agonists (DAs) Capable of alleviating all major symptoms of RLS Bromocriptine Pergolide Pramipexole Ropinerole www.wemove.org

13. Dopamine Precursors Carbidopa/levodopa available as… Sinemet ® in 10/100, 25/100, or 25/250 Sinemet ® CR in 25/100, 50/200 www.wemove.org

14. Administration of Levodopa for RLS PRN or on a regular schedule One to 2 hours before bedtime On an empty stomach, if possible www.wemove.org

15. Dosage of Carbidopa/levodopa for RLS Initially 12.5/50 mg/day to 25/100 mg/day of regular formulation for symptoms for waking with symptoms at night 25/100 mg/day of controlled-release formulation useful at bedtime/sleep onset www.wemove.org

16. Higher Doses of Levodopa Increased risk of augmentation Worsening of symptoms www.wemove.org

17. Adverse Effects of Levodopa GI symptoms: nausea and vomiting, constipation or diarrhea, anorexia Sleep disturbances: insomnia, fatigue Other: anxiety, dry mouth, flushing, headache www.wemove.org

18. Dopamine Agonists (DAs) Ergotolines –Pergolide (Permax ® ) –Bromocriptine (Parlodel ® ) Nonergotolines –Pramipexole (Mirapex ® ) –Ropinirole (Requip™) www.wemove.org

19. Ergot Derivatives Pergolide (Permax ® ) Bromocriptine (Parlodel ® ) www.wemove.org

20. Pergolide Therapy for RLS Long-acting Higher relative potency than bromocriptine Well-absorbed through GI tract www.wemove.org

21. Initiation of DA Therapy Relatively small dosage –0.05 mg for pergolide –1.25-2.50 mg for bromocriptine Slow titration upward www.wemove.org

22. Advantages of Pergolide or Bromocriptine Less augmentation than with carbidopa/levodopa First-line therapy for patient with moderate or severe RLS www.wemove.org

23. Adverse Effects Specific to Pergolide and Bromocriptine Contraindication: known hypersensitivity to ergot alkaloids Rare complications: –Pulmonary or retroperitoneal fibrosis –Pleural thickening and effusions Reddened, edematous skin changes in legs www.wemove.org

24. Nonergotoline DAs for RLS Pramipexole (Mirapex ® ) Ropinirole (Requip ® ) www.wemove.org

25. Pramipexole Targets: Several RLS Symptoms www.wemove.org

26. Key Benefits of Nonergotoline DAs Possible effectiveness in non-responders to other DAs (i.e., ergotolines) www.wemove.org

27. Initiating Pramipexole Therapy for RLS Initiate with low dose of 0.125 mg/day or lower Gradual titration to therapeutic range of 0.25 mg to 1.5 mg/day www.wemove.org

28. Adverse Effects of DAs Nausea/vomiting Orthostatic hypertension Nasal congestion Insomnia Dizziness Lightheadedness Somnolence www.wemove.org

29. Other Drugs with Dopaminergic Action Amantadine (Symmetrel®) Selegiline (Eldepryl®) www.wemove.org

30. Benzodiazepines for RLS Clonazepam (Klonopin ® ) Temazepam (Restoril ® ) Diazepam (Valium ® ) Triazolam (Halcion ® ) www.wemove.org

31. Benzodiazepine Issues for RLS Schedule C-IV controlled substances Low risk of tolerance/abuse www.wemove.org

32. Role of Benzodiazepines in RLS May be combined with dopamine agonists or carbidopa/levodopa Most benefit –Mild and intermittent symptoms –Young patients www.wemove.org

33. Daily Doses of Benzodiazepines for RLS Clonazepam: 0.75 mg Diazepam: 2.0 to 5.0 mg Triazolam: 0.125 to 0.25 mg www.wemove.org

34. AEs of Benzodiazepines Daytime somnolence “Hang over” Decreased libido Risk of falls Exacerbation of pre-existing sleep apnea Tolerance and dependency Withdrawal symptoms www.wemove.org

35. Opioids in the Treatment of RLS Propoxyphene hydrochloride (Darvon ® ) Codeine Oxycodone hydrochloride (Percocet ® or Roxicodone ® ) Methadone hydrochloride www.wemove.org

36. Administration of Opioids For RLS Oral administration Taken with food to minimize GI upset Taken at bedtime www.wemove.org

37. Adverse Effects of Opioids Nausea Constipation Mental changes Interaction with other CNS depressants Addiction www.wemove.org

38. Other Pharmacologic Agents for RLS Anticonvulsants –Carbamazepine (Tegretol ® ) –Gabapentin (Neurontin ® ) Antihypertensives –Clonidine hydrochloride (Catapres ® ) www.wemove.org

39. Other Pharmacologic Agents for RLS Antispasticity agents –Baclofen Mixed analgesics and sedative-hypnotics –Tramadol (Ultram ® ) www.wemove.org