Treatment Options for Restless Legs Syndrome (RLS)
Alpha-2-delta ligands such as pregabalin or gabapentin should be used as first-line pharmacologic therapy for RLS due to their strong efficacy and favorable long-term safety profile compared to dopaminergic agents. 1
First-Line Treatment Options
Pharmacological Options
Alpha-2-delta ligands
- Pregabalin or gabapentin
- Particularly recommended for patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD) with appropriate dose adjustment 1
- Superior long-term safety profile compared to dopaminergic agents
Iron therapy
- First-line for patients with low iron stores 1
- Recommended when:
- Ferritin ≤75 ng/mL or transferrin saturation <20%
- Oral ferrous sulfate for most patients
- IV ferric carboxymaltose for inadequate response to oral iron
- IV iron sucrose for ESRD patients with ferritin <200 ng/mL and transferrin saturation <20%
Non-Pharmacological Options
- Regular aerobic and resistance exercise 1
- Good sleep hygiene practices
- Avoidance of substances that may worsen RLS:
- Caffeine
- Alcohol
- Antihistamines
- Most antidepressants
Second-Line Treatment Options
Dopamine Agonists
- Ropinirole, pramipexole, or rotigotine patch 1, 2
- FDA-approved for RLS with demonstrated efficacy in clinical trials 2
- Recommended for short-term use only due to risk of augmentation 1
- Ropinirole clinical trials showed significant improvement in RLS symptoms:
- Mean change in IRLS scale score at Week 12 showed significant improvement over placebo
- 53.4-73.3% of patients rated as responders on CGI-I scale 2
- Requires close monitoring for signs of augmentation
Opioids
- Extended-release oxycodone 1
- Conditionally recommended for moderate to severe RLS
- Particularly for patients who have failed other therapies
- Requires monitoring for respiratory depression and central sleep apnea
Special Populations
Chronic Kidney Disease/ESRD
- Gabapentin or pregabalin (with dose adjustment) as first-line 1
- IV iron sucrose for ESRD patients with ferritin <200 ng/mL and transferrin saturation <20%
- Consider cool dialysate for patients on hemodialysis
Pregnant Patients
- Prioritize non-pharmacological approaches 1
- Careful consideration of treatment options due to different safety profiles
Children
- Iron therapy as first-line for those with low iron stores 1
- Limited data on dopaminergic medications
Managing Augmentation
Augmentation is a paradoxical worsening of RLS symptoms that occurs with dopamine agonist treatment and represents a major clinical challenge 1.
Key features of augmentation:
- Earlier onset of symptoms during the day
- Increased symptom intensity
- Shorter latency to symptom onset during rest
- Spread of symptoms to other body parts
- Shorter duration of relief from medication
Management approach:
- Gradual tapering and discontinuation of the dopamine agonist
- Transition to alpha-2-delta ligands or opioids
- Consider IV iron therapy
- Low-dose opioids are recommended for dopamine agonist-related augmentation
Monitoring and Follow-up
- Regular follow-up to assess symptom control
- Adjust treatment as needed with minimal dose increases over time
- Regular monitoring for medication side effects, particularly for patients on dopamine agonists
- Ongoing assessment for augmentation in patients on dopaminergic agents
Alternative Therapies
- Bilateral high-frequency peroneal nerve stimulation 1
- Anticonvulsants (gabapentin) for painful symptoms 3
- Benzodiazepines may improve sleep quality but have modest therapeutic effects on RLS symptoms 4
The treatment approach should follow a stepwise algorithm based on symptom severity, iron status, and comorbidities, with careful monitoring for augmentation in patients receiving dopaminergic agents.