Patients reporting alcohol dependence were better able to stay sober when treated with oral gabapentin (Neurontin) in a placebo-controlled trial, researchers said, although abstinence rates remained low. Treatment for chronic alcoholism.
The drug was associated with abstinence rates of 11.1% (95% CI 5.2%-22.2%) and 17% (95% CI 8.9%-30.1%) after 12 weeks in patients receiving 900 and 1,800 mg/day, respectively, compared with 4.1% (95% CI 1.1%-13.7%, P=0.04 for gabapentin dose effect) for those in the placebo group, according to Barbara J. Mason, PhD, of the Scripps Research Institute in La Jolla, Calif., and colleagues.
At the higher gabapentin dose, one participant remained abstinent for every eight treated in the 150-patient study, the researchers reported online in JAMA Internal Medicine.
Gabapentin also appeared to outperform placebo in the co-primary outcome measure, avoidance of heavy drinking, the researchers added.
In the group taking the higher dosage, 44.7% avoided heavy drinking (95% CI 31.4%-585.8%). The 900-mg group had an avoidance rate of 29.6% (95% CI 19.1%-42.8%), whereas the rate was 22.5% in the placebo group (95% CI 13.6%-37.2%, P=0.02 for gabapentin dose effect).
Mason and colleagues also reported that the drug produced no serious adverse effects, and that discontinuations because of adverse events were similarly uncommon in the placebo and active-drug groups.
"Larger studies in more diverse populations of patients with alcohol dependence are needed to replicate and extend these findings," the researchers wrote.
They noted that gabapentin is already a familiar drug to physicians, including those in primary care. "Thus, unlike other approved treatments for alcohol dependence that are prescribed by a small number of specialists, gabapentin may be more readily utilized by primary care physicians," Mason and colleagues wrote.
Treatment for chronic alcoholism
"Increased implementation of effective pharmacological treatment for alcohol dependence in primary care may be a major benefit of gabapentin as a treatment option for alcohol dependence," they added.
He noted that several smaller trials had previously found a benefit for gabapentin in promoting alcohol cessation in abusers, bolstering the current study's plausibility.
Gabapentin is currently approved for treating seizures and neuropathic pain. However, Mason and colleagues explained, its activity in the gamma-aminobutyric acid (GABA) neurotransmitter pathway suggested that it might alleviate alcohol craving, which is believed to involve GABAergic activation in the amygdala. Previous studies had shown that gabapentin modulates such activity.
For the current trial, Mason and colleagues recruited individuals wanting treatment for alcohol dependence via print and Internet advertisements. Those responding were screened using DSM-IV criteria for current alcohol dependence. Participants had to have stopped drinking for at least 3 days but less than 1 month prior to randomization. They also had to be generally healthy otherwise.
Individuals were excluded if they showed strong risk factors for withdrawal symptoms or if urine testing indicated recent use of commonly abused drugs.
Of the 150 randomized into the three treatment groups, about two-thirds reported not having sought alcoholism treatment previously. Mean age of participants was about 44, most were white, and roughly half were employed full time.
An oddity of randomization led to the placebo group being nearly 60% female, whereas the two active drug groups were more than 60% male.
In addition to taking daily placebo or gabapentin pills, participants also received 20 minutes of in-person counseling weekly intended to reinforce abstinence and medication compliance. Patients were encouraged to join local self-help groups and to obtain additional psychotherapy if they wished.
Participants kept diaries of their alcohol intake and also underwent weekly alcohol breath tests and monthly tests of gamma-glutamyltransferase (GGT) levels as checks on claims of abstinence. A heavy drinking day was one involving intake of four standardized drinks for women or five for men.
At baseline, those assigned to 1,800 mg/day of gabapentin reported a mean of about 1.2 heavy drinking days per week, which declined steadily to just over 0.5 per week through week 10 before suddenly jumping back to nearly 1.0.
The mean number of heavy drinking days per week in the 900-mg/day group fell from about 1.5 at baseline to 0.9 at week 12, whereas participants in the placebo group had an increase to 1.7 during study from 1.5 at baseline (P<,0.001 for gabapentin dose effect).
All three groups had sharp declines in scores on the Alcohol Craving Questionnaire, but these were somewhat steeper in the gabapentin groups (P=0.03 for dose effect). Sleep quality also improved more and depression symptoms, as measured with the Beck Depression Inventory, decreased more with gabapentin (P≤,0.001).
About 40% of patients enrolling in the study withdrew before completing the 12 weeks of treatment. Mason and colleagues classified only seven of the 65 dropouts as treatment failures, but 15 were lost to follow-up and 11 others were listed as having quit by choice. Nine withdrawals were attributed to adverse events which included fatigue, headache, and euphoria.
Nunes, in assessing the study, indicated that it was well-powered for evaluating the major endpoints. But he suggested that the requirement that participants be abstinent prior to enrolling was a significant limitation.
Treatment for severe alcoholic hepatitis
"In future research, it would be useful to determine whether the efficacy of gabapentin depends on an initial period of abstinence, and what this says about its mechanism," Nunes wrote.
He also expressed concern about the future of gabapentin as an alcoholism treatment, given that the drug is off-patent and that private sector funding for larger trials may not be available. "Approval by the FDA would be one helpful step" in increasing utilization of adjunctive drugs in this setting, Nunes wrote, but without pharmaceutical industry support, the government would have to take on the required trials.
Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner