Management of augmentation in patients with restless legs syndrome (RLS)^*

* Augmentation is the main complication of dopaminergic therapy in RLS and refers to a paradoxical worsening of symptom severity with increasing doses of medication. It should be suspected in the following circumstances:

• A maintained increase in symptom severity despite appropriate treatment or following a dose increase, particularly if a dose reduction leads to an improvement in symptoms
• Earlier onset of symptoms in the afternoon/evening
• Topographic spreading of symptoms to previously uninvolved body parts (eg, arms)
• Shorter latency to symptom onset during the day when at rest
• Shorter duration of action of the drug

¶ Long-acting dopamine agonists include rotigotine patch, extended release pramipexole, and extended release ropinirole.

Δ Mild augmentation exists when all of the following criteria are met:

• Temporal shift in symptoms
• Dopaminergic dose does not exceed maximum recommended for RLS
• Symptoms cause no more than mild distress
• There has been no prior increase in dose above what was previously therapeutically effective

◊ Maximum recommended doses of dopamine agonists for RLS:

• Pramipexole 0.5 mg/day
• Ropinirole 4 mg/day
• Rotigotine 3 mg/day

§ At this juncture, some may choose to switch to a long-acting formulation or cross-titrate to a gabapentinoid (also known as alpha-2-delta ligands), rather than increase the total dopamine dose, in an effort to minimize or eliminate long-term dopamine exposure. Cross-titration refers to adding the new agent prior to or during the dopaminergic taper.

¥ Gabapentinoids include gabapentin enacarbil, pregabalin, and gabapentin. Relative contraindications to gabapentinoid therapy include obesity, risk of falls, and comorbid depression.

† Alternative to cross-titration is a 10-day washout with re-evaluation of need for ongoing treatment before introduction of a gabapentinoid or opioid. Patients may have severe RLS symptoms and profound insomnia during washout period. Low-dose long-acting opioids may be considered in patients with a relative contraindication to a gabapentinoid who have augmentation on a long-acting dopamine agonist.