title: Augmentation and tolerance with long-term pramipexole treatment of restless legs syndrome (RLS).
abstract: BACKGROUND
  Dopaminergic agents have become first-line treatments for restless legs syndrome (RLS). The most common serious complications of L-Dopa treatment of RLS are "augmentation", in which RLS symptoms appear earlier during the day, and tolerance, in which medication effectiveness wanes over time. The aims of this study were to assess rates of augmentation and tolerance, and their interrelationship, with pramipexole treatment of RLS.
  
  
  METHODS
  Retrospective assessment of all patients (N=59) treated for RLS with pramipexole for at least 6 months (mean duration=21.2+/-11.4 months) by the senior author. Pramipexole dosing and clinical follow-up were performed in a standardized fashion. L-Dopa was discontinued and other medications for RLS were tapered as tolerated. Rates of augmentation (need for earlier administration of the same dose of pramipexole) and tolerance (need for an increase in pramipexole dose) were determined.
  
  
  RESULTS
  Augmentation developed in 32% (19/59), and tolerance occurred in 46% (27/59), of patients. These two complications were statistically related (P<0.05). The only clinical predictors of these complications were previous augmentation or tolerance to L-Dopa.
  
  
  CONCLUSIONS
  Augmentation and tolerance are more common with extended pramipexole treatment of RLS than has been previously reported in preliminary studies. However, these complications are generally manageable by earlier dosing or small dose increases of this agent, and only rarely require medication discontinuation.
authors.affiliation: Departments of Medicine and Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 1400 Centre Street, Suite 109, Newton Center, MA 02459, USA. jwinkelman@sleephealth.com
authors.forename: John W
authors.initials: JW
authors.lastname: Winkelman
authors.forename: Lindsay
authors.initials: L
authors.lastname: Johnston
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052160:Benzothiazoles; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077487:Pramipexole; D012148:Restless Legs Syndrome / Q000188:drug therapy*; D012189:Retrospective Studies; D013844:Thiazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D013844:Thiazoles; D000077487:Pramipexole