What is the initial treatment for a patient with restless leg syndrome (RLS) and normal ferritin levels?

Initial Treatment for Restless Leg Syndrome with Normal Ferritin

Alpha-2-delta ligands (pregabalin or gabapentin) are recommended as first-line pharmacologic therapy for moderate to severe RLS with normal ferritin levels due to their effectiveness and lower risk of augmentation compared to dopamine agonists. 1

Diagnostic Confirmation

Before initiating treatment, ensure the patient meets the four essential diagnostic criteria for RLS:

• An urge to move the legs accompanied by uncomfortable sensations
• Symptoms beginning or worsening during periods of rest or inactivity
• Symptoms being partially or totally relieved by movement
• Symptoms occurring only in the evening/night or being worse during these times 1

Treatment Algorithm

Step 1: Non-Pharmacological Approaches

Start with these interventions before or alongside medication:

• Regular moderate aerobic and resistance exercise
• Smoking cessation
• Alcohol avoidance
• Caffeine reduction or elimination
• Discontinuation of potentially exacerbating medications
• Proper hydration throughout the day
• Sleeping with the head of the bed elevated (10°) 1

Step 2: Pharmacological Management

First-Line Therapy:

• Alpha-2-delta ligands:
  • Pregabalin or gabapentin
  • Preferred over dopamine agonists due to lower risk of augmentation 1

Second-Line Therapy:

• Dopamine agonists (only if alpha-2-delta ligands are ineffective or not tolerated):
  • Ropinirole: Starting dose 0.25 mg orally 1-3 hours before bedtime
  • Pramipexole: Starting dose 0.125 mg orally 2-3 hours before bedtime
  • Rotigotine patch
  • Important: Use for short-term management only due to high risk of augmentation 1, 2

Third-Line Therapy:

• Opioids (for severe cases that fail to respond to first and second-line treatments):
  • Use with caution due to risk of central sleep apnea and respiratory depression 1, 3

Special Considerations

Monitoring

• Regular follow-up is necessary to assess symptom control and adjust treatment
• Start with lower doses in geriatric patients and titrate slowly
• Monitor for side effects, particularly:
  • With dopamine agonists: augmentation, orthostatic hypotension
  • With alpha-2-delta ligands: dizziness, somnolence 1

Augmentation Warning

Augmentation is a serious iatrogenic worsening of RLS characterized by:

• Earlier symptom onset
• Increased symptom intensity
• Spread of symptoms to other body parts

This occurs in approximately one-third of patients on dopamine agonists, which is why alpha-2-delta ligands are preferred as first-line therapy 1, 3

Treatment Duration

For ropinirole, clinical trials demonstrated efficacy at 12 weeks with mean doses of approximately 2 mg/day. Long-term maintenance of efficacy was demonstrated in a 36-week trial 2

Clinical Pearls

• Even though ferritin levels are normal, maintaining them at the higher end of normal may be beneficial
• The maximum dosage of ropinirole used in RLS clinical trials was 4 mg once daily 2
• For patients who develop augmentation on dopamine agonists, consider adding an alpha-2-delta agent or low-dose opioid with subsequent slow tapering of the dopamine agonist 3, 4
• Combination therapy may be necessary for refractory cases 5