Gabapentin for Alcohol-Related Disorders: Critical Appraisal of the Symptom-Driven Approach

Gabapentin, available as gabapentin and as the prodrug gabapentin enacarbil, is an approved treatment for partial seizures, postherpetic neuralgia, and the restless legs syndrome. Gabapentin has been studied for diverse off-label indications, including alcohol use disorder (AUD). Meta-analyses of randomized controlled trials (RCTs) suggest that gabapentin reduces the severity of alcohol withdrawal symptoms (AWS) as well as the percentage of heavy drinking days in persons with AUD; however, the magnitude of benefit is small, and no benefits are apparent for other drinking outcomes. Furthermore, a recent, large RCT found an extended-release formulation of gabapentin enacarbil ineffective for a wide range of drinking and other outcomes in patients with AUD. Some research suggests that gabapentin may improve drinking outcomes specifically in AUD patients with higher levels of AWS; this may be a result of gabapentin-associated reduction in AWS, precluding AWS-triggered continued drinking. In this context, a recent, large RCT found that gabapentin reduced heavy drinking and increased abstinence, and that these findings were apparent only in patients with higher levels of AWS during the 2 weeks before randomization; disconcertingly, gabapentin appeared to worsen drinking outcomes in the patients with low AWS. Whereas these findings support the conjecture that gabapentin could be considered indicated in AUD patients with high AWS, problems with this RCT and with its findings limit the applicability of the findings to everyday clinical practice. These problems are discussed in detail. It is concluded that, in line with the recommendations of a recent treatment guideline, gabapentin may be considered for patients with AUD only if first line drugs such as naltrexone and acamprosate cannot be used. It may also be worth examining benefits with gabapentin in AUD associated with chronic pain, anxiety, and chronic insomnia because gabapentin is suggested to attenuate these syndromes.