Controlled withdrawal of pramipexole after 6 months of open-label treatment in patients with restless legs syndrome

Mov Disord. 2006 Sep;21(9):1404-10. doi: 10.1002/mds.20983.


Although dopamine agonists are becoming first-line therapy for restless legs syndrome (RLS), few reports describe treatment periods exceeding 12 weeks. Here, 150 RLS patients who had responded to pramipexole during a 6-month run-in period (mean dose, 0.50 mg) were randomly assigned to receive placebo or continue receiving pramipexole at an individually optimized dose of 0.125 to 0.75 mg/day for a further 3 months. Patients switched to placebo reached the primary endpoint (a predefined worsening on both the Clinical Global Impressions-Global Improvement scale and the International RLS Study Group Rating Scale) significantly more often than patients who continued to receive pramipexole (85.5% vs. 20.5%; P < 0.0001). They also reached the primary endpoint faster, in 5 versus 42 days to a Kaplan-Meier survival estimate of 0.85 and 7 versus > 84 days to an estimate of 0.5. Over the total 9 months, clinician and patient ratings of symptoms, sleep, and quality of life identified no decline in pramipexole's benefit or tolerability. The great majority of adverse events (AEs) were mild or moderate, and of expected types. Augmentation was considered an AE, but in this population of responders it did not occur.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / adverse effects*
  • Benzothiazoles / administration & dosage*
  • Benzothiazoles / adverse effects*
  • Dopamine Agonists / administration & dosage*
  • Dopamine Agonists / adverse effects*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Long-Term Care
  • Male
  • Middle Aged
  • Patient Satisfaction
  • Pramipexole
  • Quality of Life
  • Recurrence
  • Restless Legs Syndrome / drug therapy*
  • Sleep / drug effects
  • Substance Withdrawal Syndrome / etiology*


  • Antiparkinson Agents
  • Benzothiazoles
  • Dopamine Agonists
  • Pramipexole