title: Levodopa for restless legs syndrome.
abstract: Levodopa plus dopamine decarboxylase inhibitor is a common treatment for restless legs syndrome (RLS).
  
  
  
  To evaluate efficacy and safety of levodopa for RLS compared to placebo and other active agents.
  
  
  
  We searched CENTRAL (The Cochrane Library 2008, Issue 4), MEDLINE, EMBASE, PsycINFO and CINAHL, from January 1985 to December 2008, reference lists of articles, and contacted pharmaceutical companies.
  
  
  
  We included double-blind randomised controlled trials (RCT) investigating levodopa treatment versus placebo or other treatment for at least seven days in patients with RLS (age ≥ 18 years). Outcomes included symptom severity, CGI-I, objective as well as self rated sleep parameters, quality of life, and safety parameters.
  
  
  
  Two authors extracted data, assessed risk of bias, and contacted pharmaceutical companies and authors for additional information. We collected dropouts due to adverse events and patients experiencing adverse events.
  
  
  
  Six placebo controlled and three active controlled RCTs were included (521 participants). Symptom severity (11 point rating scale, 0 points indicating no symptoms, 10 points indicating maximally severe symptoms) was more reduced with levodopa than placebo in two studies (mean difference (MD) -1.34, 95% confidence interval (CI) -2.18 to -0.5, P = 0.002). Periodic limb movements in sleep per hour of sleep (PLMS-Index; PLMSI) improved by -26.28/h compared to placebo (95% CI -30.53 to -22.02, P < 0.00001).The CGI-I changed more with levodopa than placebo in two studies (MD -1.25, 95% CI -1.89 to -0.62, P = 0.0001). In two studies, sleep quality (sleep questionnaire, visual analogue scale) showed a large effect (standardised mean difference (SMD) 0.92, 95% CI 0.52 to 1.33, P < 0.00001) whereas quality of life (50 mm Visual Analogue Scales) improved by 3.23 compared to placebo (95% CI 1.64 to 4.82, P < 0.0001). Few patients dropped out of treatment (3 of 218 patients) but more levodopa treated patients experienced adverse events than with placebo (odds ratio 2.61, 95% CI 1.35 to 5.04, P = 0.004). Two dopamine agonist controlled studies showed smaller effects with levodopa than cabergoline and pramipexole on the IRLS (MD 5.25, 95% CI 2.10 to 8.40, P =0.001), CGI-I (MD 0.62, 95% CI 0.37 to 0.87, P < 0.00001), and quality of life (MD 5.54, 95% CI 2.65 to 8.43, P = 0.0002).
  
  
  
  Levodopa is efficacious for the short-term treatment of RLS. Augmentation, the clinically most relevant adverse event, was not investigated sufficiently.
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: D015259:Dopamine Agents / Q000627:therapeutic use*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012148:Restless Legs Syndrome / Q000188:drug therapy*
chemical_list: D015259:Dopamine Agents; D007980:Levodopa