Aripiprazole, a Novel Option in the Management of Restless Legs Syndrome (RLS) Patients with Augmentation and/or Severe RLS Symptoms: A Report of 4 Cases.

Purpose: Restless Legs Syndrome (RLS) is a sensorimotor disorder associated with an unpleasant urge to move the limbs, relieved with movement, occurring in the evenings and with prolonged rest/inactivity. Treatment with dopamine agonists is effective for up to 60-90% of affected individuals. However, augmentation, ie, the paradoxical worsening of RLS symptoms after prolonged RLS treatment, is frequently reported, typically after 3-10 years of treatment. Here, we present 4 patients with RLS who were successfully treated with dopamine agonists but later developed augmentation. A trial of aripiprazole, a dopamine receptor partial agonist (DRPA), was initiated for treatment of augmentation symptoms. Patients and Methods: Four patients treated for RLS with dopamine agonists developed augmentation. In each instance, augmentation symptoms did not respond adequately to a variety of medications including α2δ drugs, opioids or other agents. A trial of aripiprazole was initiated for each patient, and effects were evaluated. Results: All four patients with severe RLS and augmentation with dopamine agonists achieved symptom control with aripiprazole. Patients endorsed 90-100% efficacy with aripiprazole by subjective self-report after failures with other agents. Further evaluation with the International Restless Legs Syndrome Study Group RLS Rating Scale (IRLS-SGRS) showed that benefits (from moderate to very severe, to mild to moderate severity) were largely maintained for 1-2 years. Aripiprazole doses to control augmentation symptoms were low (1-4 mg). No significant side effects were reported. Conclusion: Aripiprazole may have utility for augmentation in RLS. We speculate that the partial agonist and antagonist properties of aripiprazole may limit potential for dopamine hyposensitization to progress to cause augmentation. Further research is needed to see if aripiprazole and/or other DRPAs are a viable long-term treatment option for patients experiencing augmentation and/or severe RLS with dopamine agonist therapy.