Treatment for Restless Leg Syndrome
Alpha-2-delta ligands (pregabalin or gabapentin) should be used as first-line pharmacologic therapy for moderate to severe restless legs syndrome due to their effectiveness and lower risk of augmentation compared to dopamine agonists. 1
Diagnostic Criteria
Restless Legs Syndrome (RLS) is characterized by:
- An urge to move the legs accompanied by uncomfortable sensations
- Symptoms that begin or worsen during periods of rest
- Relief with movement
- Worsening of symptoms in the evening or night
Treatment Algorithm
Step 1: Laboratory Evaluation
- Check serum ferritin levels (primary priority)
- Iron supplementation recommended for:
- Ferritin levels <75 ng/mL
- Transferrin saturation <20%
Step 2: Non-Pharmacological Approaches (for mild symptoms)
- Regular aerobic and resistance exercise
- Smoking cessation
- Alcohol avoidance
- Caffeine reduction or elimination
- Discontinuation of potentially exacerbating medications
Step 3: Pharmacological Treatment (for moderate to severe symptoms)
First-Line Therapy:
- Alpha-2-delta ligands:
- Pregabalin or gabapentin
- Particularly effective for patients with CKD or ESRD
Second-Line Therapy:
Dopamine agonists (for short-term use only due to augmentation risk):
- Ropinirole: 0.25 mg orally 1-3 hours before bedtime
- Pramipexole: 0.125 mg orally 2-3 hours before bedtime
- Rotigotine patch
FDA data shows ropinirole significantly reduces RLS symptoms compared to placebo, with mean changes in IRLS scale scores of -11.0 to -13.5 vs -8.0 to -9.8 for placebo 2.
Third-Line Therapy:
- Opioids (for severe cases that fail to respond to first and second-line treatments):
- Extended-release oxycodone for severe to very severe RLS
- Use with caution due to risk of central sleep apnea and respiratory depression
Special Considerations
Iron Deficiency
- Iron deficiency is a major treatable cause of RLS
- Supplement iron when:
- Ferritin <75 ng/mL or transferrin saturation <20%
- For ESRD patients: IV iron sucrose when ferritin <200 ng/mL and transferrin saturation <20%
Augmentation Risk
- Augmentation is a paradoxical worsening of symptoms with dopaminergic treatment
- Risk is higher with dopamine agonists (30-80% of patients), particularly levodopa 1, 3
- Prevention strategies:
- Keep dopamine agonist doses as low as possible
- Use longer-acting agents (e.g., rotigotine patch)
- Maintain high serum ferritin levels
Secondary RLS
- Evaluate for common secondary causes:
- Renal disease
- Diabetes
- Pregnancy
- Medication side effects
- Thyroid disorders
Monitoring and Follow-up
- Regular monitoring for medication side effects, particularly augmentation with dopamine agonists
- Assess for earlier symptom onset, increased symptom intensity, and spread of symptoms to other body parts
- Regular follow-up to assess symptom control and adjust treatment as needed
Treatment Pitfalls to Avoid
- Failing to check ferritin levels in all RLS patients
- Long-term use of dopamine agonists without monitoring for augmentation
- Confusing RLS with mimics such as positional discomfort, leg cramps, and peripheral neuropathy
- Overlooking secondary causes of RLS
- Using quinine for nocturnal leg cramps (safety concerns)
The evidence strongly supports alpha-2-delta ligands as first-line therapy, with dopamine agonists reserved for short-term use due to augmentation risk. Iron supplementation should be considered in all patients with low ferritin levels, as this may improve symptoms and potentially lower the risk of augmentation.