Gabapentin found to be effective in treating alcohol dependence and relapse symptoms

IMPORTANCE Approved medications for alcohol dependence are prescribed for less than 9% of US alcoholics.

OBJECTIVE To determine if gabapentin, a widely prescribed generic calcium channel/γ-aminobutyric acid-modulating medication, increases rates of sustained abstinence and no heavy drinking and decreases alcohol-related insomnia, dysphoria, and craving, in a dose-dependent manner.

DESIGN, PARTICIPANTS AND SETTING A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 

men and women older than 18 years with current alcohol dependence, conducted from 2004 through 2010 at a single-site, outpatient clinical research facility adjoining a general medical hospital.

INTERVENTIONS Oral gabapentin (dosages of 0 [placebo], 900 mg, or 1800 mg/d) and concomitant manual-guided counseling.

MAIN OUTCOMES AND MEASURES Rates of complete abstinence and no heavy drinking (coprimary) and changes in mood, sleep, and craving (secondary) over the 12-week study.

RESULTS Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% (95% CI, 1.1%-13.7%) in the placebo group, 11.1% (95% CI, 5.2%-22.2%) in the 900-mg group, and 17.0% (95% CI, 8.9%-30.1%) in the 1800-mg group (P = .04 for linear dose effect; number needed to treat [NNT] = 8 for 1800 mg). The no heavy drinking rate was 22.5% (95% CI, 13.6%-37.2%) in the placebo group, 29.6% (95% CI, 19.1%-42.8%) in the 900-mg group, and 44.7% (95% CI, 31.4%-58.8%) in the 1800-mg group (P = .02 for linear dose effect; NNT = 5 for 1800 mg). Similar linear dose effects were obtained with measures of mood (F2 = 7.37; P = .001), sleep (F2 = 136; P < .001), and craving (F2 = 3.56; P = .03). There were no serious drug-related adverse events, and terminations owing to adverse events (9 of 150 participants), time in the study (mean [SD], 9.1 [3.8] weeks), and rate of study completion (85 of 150 participants) did not differ among groups.

CONCLUSIONS AND RELEVANCE Gabapentin (particularly the 1800-mg dosage) was effective in treating alcohol dependence and relapse-related symptoms of insomnia, dysphoria, and craving, with a favorable safety profile. Increased implementation of pharmacological treatment of alcohol dependence in primary care may be a major benefit of gabapentin as a treatment option for alcohol dependence.

TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00391716.

Psychiatrist Barbara J. Mason, who led the study, says gabapentin appears to work because it eases the most common withdrawal symptoms. "Gabapentin improved sleep and mood in people who were cutting down or quitting drinking," she tells Shots. Sleeplessness and anxiety are often what cause people to regress and start drinking again, she says.

Another factor in gabapentin's favor, she says, is that it isn't broken down by the liver, "an organ that's often damaged in people with alcohol dependence." Of three FDA-approved drugs for alcoholism, two pose potential liver risks, she says. Gabapentin passes from the blood through the kidney and into urine pretty much unchanged.

Like any drug, gabapentin has potential side effects. Drowsiness, nausea and blurred vision are some. And the drug hasn't been approved for treatment of alcohol dependence.

Gabapentin, sold under the brand name Neurontin, has a bit of a rocky history. In the early 2000s, Pfizer and its Parke-Davis unit got in trouble for pushing the drug for a variety of unapproved uses.

But Mason says the fact that her work is funded by the NIH, plus the fact that it's a generic formulation, will distance her work from that scandal.

"It's not magic, and making a big behavioral change is hard work," she says. But to ignore a drug that appears effective, she says, '"is not taking advantage of all the tools in the toolbox."

Still, the drug hasn't been approved by the Food and Drug Administration for use in treatment of alcohol dependence and there's no sign it will be anytime soon. --- via NPR