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.
Objectives
To determine the efficacy and safety of GABA receptor agonists in the treatment of acute stroke.
Search 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 In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical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.
Selection criteria
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.
Data collection and analysis
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.
Main 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).
Authors’ 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.
Plain language summary
Gamma aminobutyric acid (GABA) receptor agonists for acute stroke
GABA receptor agonists are a type of neuroprotective agent that may help protect the brain in the treatment of acute stroke. This class of drugs, which includes diazepam and chlormethiazole, are traditional sedatives that have been used for several decades and have been found to be beneficial in animal models of stroke. However, the sedation effect of GABA receptor agonists can be harmful for acute stroke patients with the potential risk of causing stupor. We included five trials with 3838 patients to assess the benefit and safety of GABA receptor agonists for patients with acute stroke. In conclusion, there was no convincing evidence to support the use of GABA receptor agonists for the treatment of patients with acute ischemic or hemorrhagic stroke. The most frequent adverse events of chlormethiazole were drowsiness and rhinitis.
