Gamma Aminobutyric Acid Receptor Agonists for Acute Stroke
Gamma aminobutyric acid (GABA) receptor agonists have shown to be effective in reducing infarct size and improving functional outcome in animal models of cerebral ischemia. However, the sedation effects of GABA receptor agonists limited the application in acute stroke patients because of the potential risk of stupor.
Materials and Methods
The aim of this study is to determine the efficacy and safety of GABA receptor agonists in the treatment of acute stroke.
Types of Studies
Randomized controlled trials.
Types of Participants
Acute stroke patients within 12 hours after stroke onset.
Types of Interventions
GABA receptor agonists in comparison with placebo.
Death or dependency, defined as a Barthel Index score of ≤60, or the modified Rankin Scale graded 3 to 5, and adverse events.
Functional independence, defined as Barthel Index score >60, or modified Rankin Scale <3, and neurological function measured by other stroke scales.
We included 5 trials with 3838 randomized patients. The methodological quality of the included trials was generally good, with low risk of bias. Four trials measured death and dependency at 3 months in chlormethiazole versus placebo without significant difference (2909 patients; risk ratio [RR], 1.03, 95% confidence interval [CI], 0.95–1.11). One trial measured this outcome between diazepam and placebo (849 patients; RR, 0.94; 95% CI, 0.82–1.07). In the subgroup analysis of total anterior circulation syndrome, a higher percentage of functional independence was found in the chlormethiazole group (635 patients; RR, 1.33; 95% CI, 1.09–1.64). The frequent adverse events related to chlormethiazole were somnolence (2527 patients; RR, 4.56, 95% CI, 3.50–5.95) and rhinitis (2527 patients; RR, 4.75, 95% CI, 2.67–8.46).
The results demonstrated no benefits from GABA receptor agonists for acute stroke patients compared with placebo (ie, no decreases in death or dependency were found; Figure). The subgroup analysis in total anterior circulation syndrome illustrated a positive result in functional independence. The most frequent adverse events caused by chlormethiazole were somnolence and rhinitis.
Implications for Practice
No evidence was found to support the use of GABA receptor agonists for the treatment of patients with acute stroke.
Implications for Research
Well-designed, double-blind randomized controlled trials would be required to test the efficacy of chlormethiazole in a large group of patients with total anterior circulation syndrome.
We acknowledge the help provided by the Cochrane Stroke Group. This article is based on a Cochrane Review published in The Cochrane Library 2013, Issue 2 (see http://www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and The Cochrane Library should be consulted for the most recent version of the review.1
- Received February 7, 2013.
- Accepted March 22, 2013.
- © 2013 American Heart Association, Inc.