Gabapentin for Alcohol Use Disorder: A Promising Outlook

This article was collaboratively written with Festus Durugo, a fourth-year PharmD candidate at Chicago State University College of Pharmacy.

Alcohol use disorder (AUD) is characterized by a problematic pattern of alcohol use leading to clinically significant impairment or distress, manifested in multiple psychosocial, behavioral, or physiological features.¹

Excessive alcohol use led to approximately 88,000 deaths and 2.5 million years of potential life lost annually in the United States between 2006 and 2010. In addition, 1 in 10 deaths among working adults 20 to 64 years were attributed to excessive alcohol use.²

Currently, there are 3 FDA-approved medications for AUD: naltrexone, acamprosate, and disulfiram.

• Naltrexone is considered first-line AUD treatment, though its use is limited in patients taking opioids because it acts on mu-opioid receptor, and it’s contraindicated in hepatitis or liver failure.³ Naltrexone is particularly beneficial in those with genetic susceptibility.
• Acamprosate enhances glutamate neurotransmission at the metabotropic-5 glutamate receptors. Lower doses are required in patients who weigh <60 kg and in renal impairment. Acamprosate hasn’t been proven effective in individuals who are heavy drinkers.
• Disulfiram is a second-line agent that works by causing unpleasant physiologic reactions (eg, vomiting, sweating, headaches) when alcohol is consumed, thereby deterring motivation to drink.

For years, benzodiazepines have been the gold standard treatment for alcohol withdrawal due to their well-documented efficacy.⁴ Because of their abuse potential, drug interactions with alcohol, and significant cognitive and psychomotor side effects, however, there has been growing interest in alternative therapies for this indication.

Recent study results suggest gabapentin is safe and effective for AUD treatment. It may also play an important role in preventing relapse symptoms associated with alcohol cessation.⁵

Gabapentin is already approved for variety of indications, including adjunctive treatment of partial seizures, neuropathic pain, and restless leg syndrome (as gabapentin enacarbil). It’s believed to exact its effect by blocking a specific α2δ subunit of the voltage-gated calcium channel, thereby indirectly increasing the concentration of γ-aminobutyric acid (GABA) and enhancing its activity.

In preclinical studies, gabapentin was shown to normalize stress-induced GABA activation in the amygdala associated with alcohol dependence. This mechanism provided the rational for its use in alcohol dependence.

One trial conducted in an outpatient treatment center examined the efficacy of 28-day gabapentin treatment in reducing alcohol consumption and craving. Eligible subjects were randomized to placebo or gabapentin 300 mg twice-daily. Using timeline follow-back method, a widely used objective index of alcohol consumption, the authors concluded that at day 28, the number of drinks per study day decreased in the gabapentin group.⁴

In addition, the gabapentin group reported a continued reduction in drinking from baseline, whereas the placebo group reported an increase in weekly alcohol consumption. Mean percentage of heavy drinking days and abstinence days were statistically significant in favor of the gabapentin group. Mild adverse events included insomnia or sleepiness, while study limitations included small sample size and use of diazepam with gabapentin prior to and during the treatment phase.⁴

Another 12-week trial in the outpatient setting of recently abstinent subjects assessed the rate of alcohol abstinence and no heavy drinking days, defined as 4 or more drinks per day for women or 5 or more drinks per day for men. It also evaluated number of drinks and number of heavy drinking days per week. Alcohol use, cravings, mood, sleep, and medication safety were assessed during weekly visits.⁵

Eligible subjects were randomized to receive placebo, gabapentin 300 mg thrice-daily (900 mg), or gabapentin 600 mg thrice-daily (1800 mg). Gabapentin had a significant linear dose effect on complete abstinence rate and no days of heavy drinking. In the 1800-mg group, the rate of sustained 12 weeks of abstinence was significant. The number needed to treat for abstinence from alcohol over a 12-week period with gabapentin 1800 mg was 8 and 5 for no heavy drinking, respectively. Rates of no heavy drinking per week was highest in the 1800-mg cohort. Linear dose effects related to cravings, mood, and sleep were statistically significant in the 1800 mg-group compared with other groups. Gabapentin was well-tolerated and no significant adverse effects were reported.⁵

In summary, the studies showed a significant reduction in the number of weekly drinks among patients receiving gabapentin monotherapy,⁴ as well as reduced alcohol craving, positively affected mood and sleep symptoms, and increased rates of abstinence with an 1800-mg daily dose of gabapentin.⁵ Both studies also suggest favorable safety profiles for gabapentin.

Pharmacists should bear in mind that these studies focused mainly on alcohol cravings, relapse, and abstinence. Limited data support gabapentin use in acute alcohol withdrawal symptoms, but the drug would likely be beneficial in patients after an acute withdrawal episode. Thus, gabapentin should only be used in mild alcohol withdrawal, including outpatient settings where benzodiazepines can’t be safely administered.

Although future research is required to determine optimal dosing, at this point, it seems gabapentin 600 mg thrice-daily provides the best results.

References

1. Tetrault JM, et al. Risky drinking and alcohol use disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis. UpToDate. Waltham, MA. 2016.

2. CDC. Fact Sheet - Alcohol Use and Your Health. cdc.gov/alcohol/fact-sheets/alcohol-use.htmuptodate. Updated July 25, 2016.

3. Johnson B. Pharmacotherapy for alcohol use disorder. UpToDate. Waltham, MA. 2016.

4. Furieri F, et al. Gabapentin reduces alcohol consumption and craving: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2007;68:1691-1700.

5. Mason BJ, et al. Gabapentin treatment for alcohol dependence. a randomized clinical trial. JAMA Intern Med. 2014;174(1):70-77.