Restless Legs Syndrome: Drug Therapy

Therapy target

Improvement of symptomatology

Therapy recommendations

• First-line agent
  • L-dopa + benserazide (DOPA decarboxylase inhibitor)Indication: intermittent or mild RLSimprovement with this therapy in 80-90% of cases.The lower the dose, the better it is for acute and long-term treatment success.
  • Dopamine agonists (pramipexole, ropinirole, and rotigotine) [approved for therapy of RLS] alternatively antiepileptic/anticonvulsants (pregabalin and gabapentin) [off-label therapy].
  • If L-dopa or dopamine agonists are given in high doses, overstimulation of receptors may occur and the effect of treatment may be reversed (augmentation).
• Second-line agent
  • Severe RLS symptoms and pain: opioids (low-dose sustained-release opioids); sustained-release oxycodone/naloxone.
• Compensation of iron deficiency: ferritin levels (see under laboratory diagnostics) should be determined at the start of therapy. If ferritin levels are low (< 30 µg/l) or transferrin saturation < 20% or iron deficiency anemia, iron should be substituted. The goal is a highly normal ferritin, since iron deficiency exacerbates the symptomatology in RLS and is a risk factor for augmentation (see above).For details on iron substitution, see below Iron deficiency anemia (ferrous sulfate for oral administration; ferrocarboxymaltose 500 mg or 1,000 mg single dose i. v.).
• See also under “Further therapy.”

Further notes

• Augmentation is the most important side effect of dopaminergic therapy; therefore, the dose of dopaminergic medication should be kept as low as possible.Note: Augmentation is the increase in RLS symptoms, after initially successful dopaminergic therapy. This is when the onset of symptoms is brought forward by at least 2 hours and/or symptom spread to other areas of the body. The cause is a dopaminergic overstimulation.
• Note: The degree of expression of augmentation correlates with iron deficiency (see above note on ferritin levels).
• Procedure for augmentation:
  • Light augmentation: existing medication can be increased up to the maximum approved dose; alternatively: divide dose into two smaller single doses or use sustained-release preparation
  • Severe augmentation: discontinue short-acting dopaminergic medication; continue therapy only with sustained-release preparations

RLS and pregnancy

• Occurrence of RLS in pregnant women in 15-25% of cases – preferentially in the third trimester (last trimester of pregnancy).
• Symptomatology: mainly sleep disturbances, rarely symptoms occur during the day. Examination of iron metabolism and iron substitution if necessary.
  • If ferritin levels < 30 µg/l or transferrin saturation < 20%: parenteral iron substitution after the 12th week with FCM.
• If necessary, administration of L-DOPA/carbidopa (L-DOPA decarboxylase inhibitor).
• Caveat. No use of in combination with benserazide, because of proven embryotoxic effects in pregnancy.