title: Dopamine agonists for restless legs syndrome.
abstract: BACKGROUND
  According to clinical guidelines, dopamine agonists are the first-line treatment of restless legs syndrome (RLS).
  
  
  OBJECTIVE
  To evaluate efficacy and safety of dopamine agonists for RLS.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 4), MEDLINE, EMBASE, PsycINFO and CINAHL, from January 1985 to December 2008, plus reference lists of articles. We contacted pharmaceutical companies.
  
  
  METHODS
  We included double-blind randomised controlled trials (RCTs) of dopamine agonist treatment versus placebo or other treatment for a period of at least seven days in patients with RLS (≥ 18 years). Outcomes included the International RLS Severity Rating Scale (IRLS), Clinical Global Impressions (CGI-I), polysomnography and self rated sleep quality, quality of life, daytime functioning, and safety parameters.
  
  
  METHODS
  Two reviewers extracted data separately; assessed risk of bias; and contacted pharmaceutical companies and authors for additional information. We collected dropout rates due to adverse events and experience of adverse events.
  
  
  RESULTS
  We included 35 placebo controlled and three active controlled RCTs (N = 7365). The mean reduction on the IRLS was -5.7 points lower in dopamine agonist treatment compared to placebo (95% confidence interval (CI) -6.7 to -4.7). Periodic limb movements in sleep per hour of sleep (PLMS-Index; PLMSI) were -22.4/h lower than in placebo (95% CI -27.8 to -16.9). Self rated quality of sleep and disease specific quality of life were improved by a standardised mean difference (SMD) of 0.40 (95% CI 0.33 to 0.47) and 0.34 (95% CI 0.23 to 0.44), respectively. Patients were more likely to drop out (odds ratio (OR) 1.82, 95% CI 1.35 to 2.45) and experienced more adverse events under dopamine agonist treatment than with placebo (OR 1.82, 95% CI 1.59 to 2.08). Visual inspection of forest plots showed the highest efficacy in three studies investigating cabergoline and pergolide (N = 3). Active controlled trials investigated effects of cabergoline, pergolide, and pramipexole in a number of outcomes. The IRLS score was lower with cabergoline and pramipexole compared to levodopa (MD -5.3, 95% CI -8.4 to -2.1). Only four studies investigated treatment efficacy up to seven months. The most severe side effect, augmentation, was not assessed reliably.
  
  
  CONCLUSIONS
  The meta-analyses show the superiority of dopamine agonists over placebo in RCTs up to seven months. Cabergoline and pramipexole showed larger efficacy compared to levodopa in some but not all outcomes.
authors.affiliation: Interdisciplinary Pain Canter, University Medical Center, Freiburg, Breisacher Strasse, 64, Freiburg, Germany, 79106.
authors.forename: Hanna
authors.initials: H
authors.lastname: Scholz
authors.forename: Claudia
authors.initials: C
authors.lastname: Trenkwalder
authors.forename: Ralf
authors.initials: R
authors.lastname: Kohnen
authors.forename: Dieter
authors.initials: D
authors.lastname: Riemann
authors.forename: Levente
authors.initials: L
authors.lastname: Kriston
authors.forename: Magdolna
authors.initials: M
authors.lastname: Hornyak
mesh_terms: D052160:Benzothiazoles / Q000627:therapeutic use; D000077465:Cabergoline; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004873:Ergolines / Q000627:therapeutic use; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D010479:Pergolide / Q000627:therapeutic use; D000077487:Pramipexole; D016032:Randomized Controlled Trials as Topic; D012148:Restless Legs Syndrome / Q000188:drug therapy*; D012720:Severity of Illness Index
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D004873:Ergolines; D010479:Pergolide; D007980:Levodopa; D000077487:Pramipexole; D000077465:Cabergoline