Gabapentin Improves Outcome in Alcoholism

Molecular Model of GABA

Improving abstinence rates in alcoholism continues to be a goal of treatment research. Several novel drug treatment strategies in alcoholism have targeted the neurotransmitter gamma-aminobutryic acid or GABA. GABA is the major inhibitor neurotransmitter in the brain.  Alcohol has effects through the GABA receptor.  Alcohol withdrawal is typically treated with the sedative drug class of benzodiazepines known to have effects on GABA receptors.  There are two main types of CNS GABA receptors GABA(A) and GABA(B).

Here is summary of drugs known to have effects through GABA and the GABA receptor:
GABA analogues: gabapentin, pregabalin
GABA(A) agonists (activators): alcohol, benzodiazepines, barbiturates,carisoprodol (SOMA), propofol, kava, valerian
GABA (A) antagonists (inhibitors):  flumazenil
GABA(B) agonists: baclofen
GABA(B) antagonists:phaclofen
GABA reuptake inhibitors (activators): tiagabine

Naltrexone (an opioid receptor antagonist) has an FDA indication for alcohol dependence in the United States.  However, a significant number of patients taking naltrexone for alcohol dependence do relapse, so successful augmentation strategies are necessary. A recent randomized clinical has been published online at the American Journal of Psychiatry looking at augmentation of naltrexone with gabapentin in alcohol dependence.  Here are the key elements of the study design:

Molecular Model of Gabapentin

Inclusion criteria: DSM-IV alcohol dependence, consuming 5 or more drinks per day (4 for women), able to enter study with a minimum of 4 days of abstinence
Exclusion criteria: current suicidal or homicidal ideation, no drug dependence, use of illicit drugs in last 30 days, positive urine drug screen, psychotropic or anticonvulsant drug use, medical problems including elevated liver enzymes
Random drug assignments: placebo, naltrexone 50 mg, naltrexone 50 mg plus gabapentin up to 1200 mg daily

The study found that the combined medication group was less likely to relapse to at least one heavy drinking day through six weeks (33% vs about 50% for both placebo and naltrexone alone).  Biomarkers of drinking also favored the combined group suggesting validity to the self-reported drinking history finding.  Interestingly, the combined gabapentin/naltrexone group reported the fewest complaints about sleep during the study.  Sleep complaints correlated with number of heavy drinking days. Additionally, gabapentin augmentation appeared to also be most beneficial in subjects with a history of alcohol withdrawal.

Gabapentin was withdrawn after six weeks and the drinking outcome improvement in the combined group waned in the ensuing 10 weeks of follow up.   This suggests that longer term treatment with gabapentin may be necessary to sustain the original superior reponse.

Although, this study is not large enough to change practice guidelines the results are encouraging and need replication.  Gabapentin is currently available (and in generic form) and approved for the treatment of seizures. If confirmed effective in alcoholism gabapentin could provide clinicians with another safe medication option.

Molecular Model of GABA From Creative Commons file--source Wikipedia author Ben Mills
Molecular Model of Gabapentin From Creative Commons file--source Wikipedia, author Fvasconellos

Anton RF, Myrick H, Wright TM, Latham PK, Baros AM, Waid LR, & Randall PK (2011). Gabapentin Combined With Naltrexone for the Treatment of Alcohol Dependence. The American journal of psychiatry PMID: 21454917