title: Gamma aminobutyric acid (GABA) receptor agonists for acute stroke.
abstract: BACKGROUND
  Gamma aminobutyric acid (GABA) receptor agonists have been shown to have a neuroprotectant effect in reducing infarct size and improving functional outcome in animal models of cerebral ischemia. However, the sedation effects of GABA receptor agonists have limited their wider application in acute stroke patients due to the potential risk of stupor.
  
  
  OBJECTIVE
  To determine the efficacy and safety of GABA receptor agonists in the treatment of acute stroke.
  
  
  METHODS
  We searched the Cochrane Stroke Group Trials Register (February 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 5), MEDLINE (1949 to June 2014), EMBASE (1980 to June 2014), CINAHL (1982 to June 2014), AMED (1985 to June 2014) and 11 Chinese databases (June 2014). In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical companies.
  
  
  METHODS
  We included randomized controlled trials (RCTs) investigating GABA receptor agonists versus placebo for acute stroke patients (within 12 hours after stroke onset), with the outcomes of death or dependency, functional independence and adverse events.
  
  
  METHODS
  Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy and assessed the methodological quality.
  
  
  RESULTS
  We included five trials with 3838 patients. The methodological quality of the included trials was generally good, with low risk of bias. Four trials measured death and dependency at three months in chlormethiazole versus placebo without significant difference (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.95 to 1.11). One trial measured this outcome between diazepam and placebo (RR 0.94, 95% CI 0.82 to 1.07). In the subgroup analysis of total anterior circulation syndrome (TACS), a higher percentage of functional independence was found in the chlormethiazole group (RR 1.33, 95% CI 1.09 to 1.64). The frequent adverse events related to chlormethiazole were somnolence (RR 4.56, 95% CI 3.50 to 5.95) and rhinitis (RR 4.75, 95% CI 2.67 to 8.46).
  
  
  CONCLUSIONS
  This review does not provide the evidence to support the use of GABA receptor agonists (chlormethiazole or diazepam) for the treatment of patients with acute ischemic or hemorrhagic stroke. Chlormethiazole appeared to be beneficial in improving functional independence in patients with TACS according to the subgroup analysis, but this result must be interpreted with great caution. More well-designed RCTs with large samples of TACS would be required for further confirmation. However, somnolence and rhinitis are frequent adverse events related to chlormethiazole.
authors.affiliation: Department of Geriatric Neurology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, China, 100853.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Lu-Ning
authors.initials: LN
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D002719:Chlormethiazole / Q000009:adverse effects / Q000627:therapeutic use*; D003975:Diazepam / Q000627:therapeutic use*; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D018755:GABA Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012220:Rhinitis / Q000139:chemically induced; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality
chemical_list: D018755:GABA Agonists; D018696:Neuroprotective Agents; D002719:Chlormethiazole; D003975:Diazepam