1. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. In the Clinic Restless Legs Syndrome

2. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. What is RLS?  Diagnostic criteria (all criteria must be met)  Urge to move legs, usually accompanied by uncomfortable, unpleasant sensations in legs  Begins or worsens during rest or inactivity  Partially or totally relieved by movement  Only occurs or worsens in the evening or night  Not attributable to another condition

3. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. What symptoms should prompt clinicians to consider RLS?  Insomnia  Urge to move the legs or leg dysesthesia  Other common symptoms  Leg pain  Fatigue  Leg jerks  Daytime sleepiness

4. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. What physical examination findings indicate possible RLS?  No physical findings are associated with idiopathic RLS  RLS may accompany  Low iron stores  Pregnancy  Renal disease  Diabetes  Neuropathy

5. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. What other evaluation should be performed in patients suspected of having RLS?  Assess  Timing and severity of RLS symptoms  Impact on daytime mood and function  Medical history  Symptoms of other sleep disorders  Family history  Medication use  Some experts recommend iron studies, even in absence of anemia continued…

6. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1.  Common mimics  Leg cramps  Neuropathy  Arthritis  Peripheral vascular disease  Akathisia  Refer to sleep specialist or neurologist  Uncertain diagnosis or coexisting sleep disorder  Neurologic disorder or other complex medical condition

7. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. CLINICAL BOTTOM LINE: Diagnosis...  Diagnosis is based on clinical criteria  Symptom timing, frequency, and severity are important  History and physical exam distinguishes RLS from mimics  Other diagnostic studies only for possible associated conditions (iron deficiency)

8. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. What nondrug therapies should clinicians recommend for RLS?  Distracting activities  Mental-alerting strategies (knitting, video games)  Activities requiring standing, locomotion, movement  Activities that may improve symptoms  Pneumatic compression devices  Near-infrared light-treatment  Aerobic or resistance training, intradialytic exercise  Avoid drugs that might provoke RLS  Avoid sleep deprivation  The role of supplemental iron is uncertain

9. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. How should clinicians choose and dose drugs?  Mild or intermittent symptoms  Only use pharmacologic therapy for situations that limit mobility (e.g., air travel)  Moderate or severe symptoms that interfere with sleep or impair daytime functioning  Reserve drugs for those with near daily or daily symptoms  Dopamine agonists (pramipexole, ropinorole, rotigotine)  Alpha-2 delta ligands (gabapentin encarbil)  Off label: other alpha-2 delta ligands and opioids

10. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. Dopamine agonists  Recommended for patients with very severe RLS, comorbid depression/dysthymia, and obesity/metabolic syndrome  Initiate with lowest recommended dose  Don’t exceed in 24-hour period: 1 mg pramipexole; 4 mg ropinirole; 3 mg rotigotine  For pramipexole and ropinirole: take 1-2 hours before expected symptom onset  Side effects: nausea, somnolence, and site application reactions with rotigotine, impulse control disorders  Augmentation is possible  Worsening of symptoms earlier in the day  Increased intensity or spread of symptoms to the arms

11. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. Alpha-2 delta ligands  Recommended for patients with comorbid pain, anxiety, insomnia, or previous impulse control disorder or addiction  Gabapentin is poorly absorbed  Gabapentin encarbil is a pro-drug that provides better bioavailability and is FDA-approved for RLS  Pregabalin is another option  Adverse effects include dizziness, somnolence, weight gain, and depression/suicidal ideation

12. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. Other Medications  Benzodiazepines generally ineffective for RLS  Opioids not well-studied for RLS  Potential to improve symptoms but high rate of AEs  Only consider after other strategies are exhausted and potential for misuse is carefully assessed  Consult with a sleep specialist before prescribing

13. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. How should clinicians monitor patients?  Titrate to lowest effective dose  Monitor for side effects and augmentation  Reassess patients who don’t improve for changes in aggravating factors  Beware of rebound with shorter-acting medications  Consider natural disease progression and variation  If augmentation occurs, split dose or switch to longer- acting agent in same class  Consider substituting alpha-2 delta ligand or high-potency opioid for dopaminergic agent

14. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. When should clinicians consider consulting a sleep specialist or neurologist?  Atypical presentation of symptoms  Loss of treatment efficacy despite increased dosage  Intolerable side effects  Augmentation  Coexisting sleep disorder, neurologic disorder, or other complex medical conditions

15. © Copyright Annals of Internal Medicine, 2009 Ann Int Med. 163 (6): ITC6-1. CLINICAL BOTTOM LINE: Treatment...  Nonpharmacologic therapies  Distracting activities  Planned ambulation  Avoiding putative triggers may not alleviate symptoms  Consider iron supplementation on a case-by-case basis  Pharmacologic treatment  Only for moderate-severe and bothersome symptoms  Start with alpha-2 delta ligands  Dose prior to expected symptom onset and titrate to lowest effective dose  Monitor for side effects  Refer patients with loss of efficacy, adverse effects, or augmentation to a sleep specialist or neurologist