BACKGROUND AND AIMS: Anti-seizure medications (ASMs) have been used historically as treatment options in alcohol withdrawal syndrome (AWS). In the past 10 years, there have been no large-scale meta-analyses comparing ASMs with placebo or the current AWS treatment standard, benzodiazepines. We aimed to evaluate the efficacy and tolerability of ASMs in AWS.

METHODS: Systematic review and meta-analysis of randomised controlled trials (RCTs) via searching Medline, Embase, and PsychINFO from database inception to March 2020 involving adults aged >18 years with AWS. We included 24 RCTs reporting on a total of 2223 participants. Efficacy outcomes included the number of participants experiencing AWS related seizures or delirium, Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) score reduction, and rescue medication requirements. Tolerability outcomes included adverse event rate and dropout due to adverse events, alongside severe, and life-threatening adverse event rates. Quality was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

RESULTS: There was no evidence of significant improvements in any efficacy outcomes when comparing ASMs with placebo or benzodiazepines. When compared with benzodiazepines, ASMs demonstrated significantly increased odds of requiring rescue medications (OR: 3.50, 95%CI: 1.32-9.28; p=0.012). When comparing ASMs with placebo, there were significantly more dropouts due to adverse events (OR: 1.86, 95% CI: 1.05, 3.28; p=0.034). Most results were of very low quality with the majority of included studies conducted before 2000.

CONCLUSIONS: This systematic review and meta-analysis found no evidence to support general first line clinical use of anti-seizure medications in alcohol withdrawal syndrome treatment.