Beyond benzodiazepines: a meta-analysis and narrative synthesis of the efficacy and safety of alternative options for alcohol withdrawal syndrome management

Purpose: To compare the efficacy and safety of non-benzodiazepines (non-BZDs) to benzodiazepines (BZDs) in the treatment of alcohol withdrawal syndrome (AWS).

Methods: For relevant literature, Google Scholar, PubMed, Embase, OVID MEDLINE, EBSCO, Cochrane Central Registry of Controlled Trials, Web of Science, and Scopus were searched. Randomized control trials (RCTs) were included, omitted were nonblinded trials, blinded trials that were not randomized, and open-label studies. The Effective Public Health Practice Project Quality Assessment was used to assess the trial's quality. A meta-analysis and a narrative synthesis were carried out.

Results: Twenty non-BZDs and five BZDs were investigated in thirty RCTs. Meta-analysis favored gabapentin over chlordiazepoxide and lorazepam (d = 0.563, p < 0.001) and carbamazepine over oxazepam and lorazepam (d = 0.376, p = 0.029), for reducing Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale scores. Eleven non-BZDs fared better than BZDs for reducing CIWA-Ar, Total Severity Assessment, Selective Severity Assessment, Borg and Weinholdt, and Gross Rating Scale for Alcohol Withdrawal scores. Eight non-BZDs outmatched BZDs regarding autonomic, motor, awareness, and psychiatric symptoms. Sedation and fatigue were prevalent in BZDs, while seizures were prevalent in non-BZDs.

Conclusion: For AWS treatments, non-BZDs are superior to or equally effective as BZDs. Non-BZD adverse events warrant further investigation. Agents that inhibit gated ion channels are promising candidates.

Protocol registration: PROSPERO CRD42022384875.