Treatment Options for Restless Leg Syndrome
Alpha-2-delta ligands (pregabalin or gabapentin) should be used as first-line pharmacologic therapy for moderate to severe RLS due to their effectiveness and lower risk of augmentation compared to dopamine agonists. 1
Diagnostic Criteria
Before initiating treatment, confirm RLS diagnosis using these four essential criteria:
- Urge to move the legs accompanied by uncomfortable sensations
- Symptoms begin or worsen during periods of rest/inactivity
- Symptoms partially or totally relieved by movement
- Symptoms occur only in evening/night or are worse during these times
Initial Evaluation
- Check ferritin levels (priority lab test)
- Values <50 ng/mL suggest need for iron supplementation 1
- Consider additional testing to rule out secondary causes:
- Complete blood count
- Basic metabolic panel
- Liver function tests
- Thyroid function tests
- HbA1c
- Urine albumin:creatinine ratio
Treatment Algorithm
Step 1: Non-Pharmacological Approaches
- Regular aerobic and resistance exercise
- Smoking cessation
- Alcohol avoidance
- Caffeine reduction/elimination
- Discontinuation of potentially exacerbating medications
- Proper hydration throughout the day
- Sleeping with head of bed elevated (10°)
- Compression stockings if venous pooling suspected
Step 2: Iron Supplementation
- For patients with ferritin <50 ng/mL
- For ESRD patients with ferritin <200 ng/mL and transferrin saturation <20%, consider IV iron sucrose
Step 3: Pharmacological Treatment for Moderate to Severe RLS
First-Line:
- Alpha-2-delta ligands:
- Pregabalin or gabapentin
- Particularly indicated for patients with CKD or ESRD
Second-Line:
- Dopamine agonists (short-term use only due to augmentation risk):
Third-Line:
- Opioids for severe cases that fail to respond to first and second-line treatments:
- Extended-release oxycodone for severe to very severe RLS 1
- Use with caution due to risk of central sleep apnea and respiratory depression
Special Populations
Patients with CKD/ESRD:
- Gabapentin as first-line treatment
- Consider vitamin C supplementation
- Consider cool dialysate for patients on hemodialysis
Geriatric patients:
- Start with lower doses
- Titrate slowly
- Monitor for orthostatic hypotension with dopamine agonists
Monitoring and Follow-up
- Regular monitoring for medication side effects
- Watch for augmentation with dopamine agonists (characterized by earlier symptom onset, increased symptom intensity, and spread of symptoms to other body parts)
- If augmentation occurs:
- Add an alpha-2-delta ligand or opioid
- Once adequate symptom relief is achieved with the second agent, very slowly down-titrate and discontinue the dopamine agonist 3
Treatment Efficacy
Clinical trials of ropinirole demonstrated significant improvement in RLS symptoms compared to placebo:
- Mean change in IRLS scale scores at Week 12 showed improvement of 11-13.5 points with ropinirole versus 8-9.8 points with placebo 2
- 53-73% of patients on ropinirole were rated as responders on CGI-I versus 40-57% on placebo 2
Common Pitfalls
Augmentation risk with dopamine agonists: Keep doses as low as possible, use longer-acting agents when possible, and maintain high serum ferritin levels to help prevent augmentation 4
Overlooking iron deficiency: Always check ferritin levels and supplement when <50 ng/mL
Mistaking RLS for similar conditions:
- Peripheral neuropathies (constant symptoms vs. circadian in RLS)
- Vascular disease/claudication (pain with exercise vs. rest in RLS)
- Nocturnal leg cramps (sudden painful contractions vs. urge to move in RLS)
- Positional discomfort (relieved by position change vs. movement in RLS)
- Arthritis (joint-specific vs. generalized symptoms in RLS)