Gabapentin’s anxiolytic and sedative properties along with its overall safety profile suggest that it may be a viable adjuvant to lorazepam in the management of acute alcohol withdrawal.

By Christopher Wilming, Mariah Alford, and Lynnette Klaus

On average, the required benzodiazepine dosage was lower with concomitant use of gabapentin in acute alcohol withdrawal  (AWS) management, according to an article appearing this month in FEDERAL PRACTITIONER. The duration for patients on alcohol withdrawal protocol was not reduced with use of gabapentin. Between group (ie, history of withdrawal seizures, blood alcohol level) and among group (ie, gabapentin administration) differences prevent direct correlations to be drawn from this evaluation. Future reviews should include power analysis to establish an appropriate sample size to determine statistical significance among identified covariates. Further evaluation of the use of gabapentin for withdrawal management is warranted prior to incorporating its routine use in the current standard of care for patients experiencing acute AWS.

Benzodiazepines remain the standard of care for management of moderate-to-severe symptoms of AWS. Strong evidence supports the use of benzodiazepines to reduce withdrawal severity, incidence of delirium, and seizures in AWS by enhancing GABA activity. However, the adverse effect (AE) burden associated with benzodiazepines can be a major limitation throughout care. Benzodiazepines also may be limited in their use in select patient popula- tions, such as in older adults or patients who present with hepatic dysfunction due to the risk of increased AEs or metabolite accumulation. A high dosing requirement of benzodiazepine for symptom management can lead to oversedation to the point of requiring intubation, increasing length of stay in the intensive care unit (ICU), and the risk of nosocomial infections.

Anticonvulsants, such as carbamazepine, valproic acid, and gabapentin, have shown to be superior to placebo and equal in efficacy to benzodiazepines for symptom management in mild-to-moderate alcohol withdrawal in both inpatient and outpatient settings. However, these agents are not recommended as first- line monotherapy due to the limited number of randomized trials supporting their efficacy over benzodiazepines in preventing severe symptoms of withdrawal, such as seizures or delirium. Nonetheless, the mechanism of action of anticonvulsants may help raise seizure threshold in patients and provide a benzodiazepine-sparing effect by enhancing GABAergic activity and lowering neuronal excitability.

Gabapentin makes an attractive agent for clinical use because of its anxiolytic and sedative properties that can be used to potentially target symptoms analogous with AWS when the use of benzodiazepines becomes a safety concern. Although similar in chemical structure, gabapentin is not metabolized to GABA and does not directly interact with the receptor. Gabapentin may increase GABA concentrations by direct synthesis of GABA and indirectly through interaction with voltage-gated calcium channels. In addition to its overall safety profile, gabapentin may be a viable adjuvant because emerging data may suggest a potential role in the management of acute alcohol withdrawal.

SOURCE: FEDERAL PRACTITIONER, March 2018