Restless Legs Syndrome

Dopamine Receptor Agonists

Dopaminergic receptor agonists are first-line therapy in the treatment of moderate to severe RLS; these drugs are also effective in the treatment of mild or intermittent RLS that is not responsive to nonpharmacologic intervention (Table 8). Dopamine receptor agonists bind to dopamine receptors, producing dopamine-like effects. The medications studied most thoroughly for use in RLS include the nonergot derivatives pramipexole dihydrochloride191-202 and ropinirole hydrochloride.170,174,176-179,203-206 Rotigotine (Neupro from UCB Pharma), nonergot dopamine receptor agonist that is delivered transdermally via a patch, is approved for the treatment of Parkinson disease and is being studied for use in RLS.207,208

Ropinirole is metabolized in the liver and has potential interaction with the P450 isozyme CYP1A2. The safety and efficacy of ropinirole at doses greater than 4 mg per day have not been established. Pramipexole is excreted through the kidneys; therefore, dosage adjustments may be necessary for patients with renal insufficiency (i.e., creatinine clearance 20-60 mL/min). There is no evidence that total daily doses of pramipexole greater than 0.5 mg provide additional benefit. In certain clinical situations, however, higher doses or ropinirole and pramipexole have been used. Complete eradication of symptoms often requires treatment with dopamine agonists combined with aggressive correction of serum ferritin levels to higher than 50 ng/mL.

Excessive daytime somnolence and an increased rate of novelty-seeking or sexual behaviors have been identified in some patients taking dopamine agonists.209,210 Patients should be cautioned to refrain from driving a motor vehicle or operating heavy machinery when therapy is instituted with these medications and until the patients can assess whether they will be adversely affected.