What are the treatment options for Restless Legs Syndrome (RLS)?

From the Guidelines

The most effective treatment for Restless Legs Syndrome (RLS) is the use of gabapentin enacarbil, as recommended by the American Academy of Sleep Medicine (AASM) with a strong recommendation and moderate certainty of evidence 1. The treatment of RLS involves a combination of lifestyle changes and medications. For mild RLS, lifestyle changes such as regular exercise, maintaining good sleep habits, avoiding caffeine and alcohol, and practicing relaxation techniques like warm baths before bedtime are recommended.

Medication Treatment Options

The following medications are suggested for the treatment of RLS:

• Ferrous sulfate, which is recommended for adults with RLS and appropriate iron status 1
• Gabapentin, which is recommended for adults with RLS 1
• Pregabalin, which is recommended for adults with RLS 1
• IV ferric carboxymaltose, which is recommended for adults with RLS and appropriate iron status 1

Important Considerations

It is essential to note that the AASM suggests against the standard use of certain medications, including:

• Levodopa, due to the risk of augmentation 1
• Pramipexole, due to the risk of augmentation 1
• Ropinirole, due to the risk of augmentation 1
• Transdermal rotigotine, due to the risk of augmentation 1
• Bupropion, carbamazepine, clonazepam, and valproic acid, due to a lack of evidence or potential adverse effects 1 In adults with RLS and end-stage renal disease (ESRD), the AASM suggests the use of gabapentin, IV iron sucrose, and vitamin C 1.

Key Recommendations

• Gabapentin enacarbil is the most effective treatment for RLS, with a strong recommendation and moderate certainty of evidence 1.
• Ferrous sulfate is recommended for adults with RLS and appropriate iron status 1.
• Gabapentin and pregabalin are recommended for adults with RLS 1.
• IV ferric carboxymaltose is recommended for adults with RLS and appropriate iron status 1.

From the FDA Drug Label

The effectiveness of ropinirole in the treatment of RLS was demonstrated in randomized, double-blind, placebo-controlled trials in adults diagnosed with RLS using the International Restless Legs Syndrome Study Group diagnostic criteria Patients were required to have a history of a minimum of 15 RLS episodes/month during the previous month and a total score of ≥15 on the International RLS Rating Scale (IRLS scale) at baseline. All trials employed flexible dosing, with patients initiating therapy at 0.25 mg ropinirole once daily. Patients were titrated based on clinical response and tolerability over 7 weeks to a maximum of 4 mg once daily.

Treatment options for Restless Legs Syndrome (RLS) include:

• Ropinirole: a dopamine agonist that has been shown to be effective in reducing symptoms of RLS, with a recommended dosage of 0.25 mg to 4 mg once daily, taken 1 to 3 hours before bedtime 2 2
• Flexible dosing: patients can be titrated to an optimal dose based on clinical response and tolerability
• Long-term maintenance: ropinirole has been shown to maintain efficacy in the treatment of RLS over a 36-week period 2 2

From the Research

Treatment Options for Restless Legs Syndrome (RLS)

The treatment options for RLS can be categorized into pharmacological and non-pharmacological approaches.

• Pharmacological treatments include:
  • Dopaminergic medications such as pramipexole, ropinirole, rotigotine transdermal patch, and levodopa 3, 4
  • Alpha2-delta calcium channel ligands (A2Ds) like gabapentin, pregabalin, and gabapentin enacarbil 5, 3, 6
  • Opioids such as codeine, tramadol, and oxycodone 3, 6
  • Oral or IV iron supplementation for patients with low normal serum indexes 5, 3, 7
• Non-pharmacological treatments include:
  • Regular physical activity 7
  • Identification and treatment of underlying conditions that may worsen RLS, such as iron deficiency, antidepressant or antihistamine administration, and OSA 5
  • Lifestyle modifications, although there is insufficient evidence to recommend specific changes 3, 7

Management of RLS Symptoms

It is essential to address factors that worsen RLS symptoms and to keep doses of dopamine agonists to the minimum required for acceptable symptom reduction 5, 3.

• Augmentation, a progressive worsening of RLS symptoms, is a common problem in treatment, and prevention is a primary goal in RLS management 5, 3, 6
• Substitution of an A2D or opioid for a dopamine agonist may be necessary if augmentation occurs 5, 6
• Treatment withdrawal and prescription of alternate medication may also be required in cases of augmentation 3