Understanding Restless Legs Syndrome: Symptoms, Diagnosis, and Treatment

1. Restless Legs Syndrome

2. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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