Efficacy and Safety of Anticonvulsants for the Inpatient Treatment of Alcohol Withdrawal Syndrome: A Systematic Review and Meta-analysis

Abstract

Aim To examine the efficacy and safety of antiepileptic drugs (AED) for the inpatient treatment of patients with moderate to severe alcohol withdrawal syndrome (AWS). Methods We searched in databases and gray literature to include randomized controlled clinical trials in adults that compare the use of AED versus placebo or any other medication. Studies that did not specify severity or were performed on an outpatient basis were excluded. The outcomes were improvement of symptoms, delirium tremens, seizures and adverse events. Two researchers independently selected the references, extracted the data and assessed the risk of bias. A qualitative synthesis was made and, when the heterogeneity was mild or moderate, a meta-analysis was performed. The quality of the evidence obtained was evaluated with the Grading of Recommendations Assessment, Development and Evaluation tool. Results In total, 26 studies with 1709 patients were included. No benefit is described in withdrawal syndrome severity measured by scales or in the development of delirium tremens. The only possible meta-analysis showed that there are no differences in the incidence of seizures (risk ratio [RR] = 1.0; confidence interval (CI) 95% 0.76–1.33), even when compared with placebo (RR = 0.95; CI95% 0.57–1.57). There were also no differences in adverse events, although a higher proportion of some mild cases were described with the use of carbamazepine and valproic acid. Conclusions The routine use of AED is not suggested in the treatment of patients with moderate or severe AWS unless indicated for comorbidity (weak recommendation against using moderate quality of evidence).

Prevention of alcohol withdrawal syndrome in the surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document

“…A recent systematic review and meta-analysis evaluated 26 randomized controlled trials comparing various AEDs to benzodiazepines or placebo. 58 The review found no difference in rate of AWS, seizure, or DTs. There was a non-statistically significant increase in the rate of mild or moderate adverse effects (dizziness, ataxia, nausea, and vomiting) with carbamazepine and valproic acid use.…”

“…Although the overall quality of evidence was low as analyzed by the cited systematic review and meta-analysis, the use of AEDs is not recommended for prophylaxis or treatment of patients with AWS. 58 …”

“…AEDs have a lower potential for abuse and act at targets outside the GABA pathway. A recent systematic review and meta-analysis evaluated 26 randomized controlled trials comparing various AEDs to benzodiazepines or placebo 58. The review found no difference in rate of AWS, seizure, or DTs.…”

“…There was a non-statistically significant increase in the rate of mild or moderate adverse effects (dizziness, ataxia, nausea, and vomiting) with carbamazepine and valproic acid use. Although the overall quality of evidence was low as analyzed by the cited systematic review and meta-analysis, the use of AEDs is not recommended for prophylaxis or treatment of patients with AWS 58…”

From consumption to withdrawal: A broad synopsis of the effects of alcohol

“…In addition, repeated alcohol withdrawal episodes increase neuronal sensitivity and excitability, a phenomenon called "kindling" which leads to more severe and lasting withdrawal symptoms [55,56]. The reduction of kindling can alleviate symptoms, complications, and sequelae related to alcohol withdrawal syndrome (AWS) [55,57,58]. This phenomenon is not unique to humans and has been observed in relevant studies on other animals.…”