Long-term treatment of restless legs syndrome with dopamine agonists.

Background: Controlled clinical trials robustly demonstrate the short-term efficacy of dopamine agonists (DA) for restless legs syndrome (RLS), but little is known about the long-term efficacy and long-term adverse events. Augmentation-an increase in the duration, intensity, and anatomy of RLS symptoms-is commonly associated with dopaminergic treatments; however, risk factors for this troubling scenario have not been formally evaluated.

Objectives: To evaluate the long-term efficacy and tolerability of DA for RLS and to evaluate factors that could predict the occurrence of augmentation.

Methods: We queried all subjects seen from 1996 to 2003 and followed up those initiated on any DA by the Baylor College of Medicine Movement Disorders Clinic, Houston, Tex. Patients with Parkinson disease, uremia, or medications that could affect RLS were excluded. Demographics, efficacy, dosing, adverse events, and augmentation were tracked across time. Statistical modeling was used to evaluate for factors that could predict augmentation.

Results: After eliminating all patients with RLS who had factors that could affect DA dosing or the accuracy of data, we observed 83 subjects with at least 6 months' use of DA (mean +/- SD, 39.2 +/- 20.9 months). Efficacy was maintained across time but at the expense of moderate but significant increases in doses (P<.01). Adverse events were frequent but usually mild and seldom resulted in discontinuation. Augmentation was frequent (48% of subjects) but usually modest, and it was predicted by a positive family history for RLS and especially the lack of any neuropathy on electromyographic or nerve conduction velocity tests.

Conclusions: Dopamine agonists continued to effectively treat RLS without long-term adverse events but often required adjustments across time. The higher rate of augmentation in familial and nonneuropathic RLS should be considered when initiating therapy.