Baclofen May Effectively Treat Alcohol Dependence

AMSTERDAM – The gamma-aminobutryric acid (GABA) receptor agonist baclofen, which is indicated for the treatment of spasticity, might represent a novel and effective drug treatment for alcohol dependence, according to an addiction specialist who presented evidence for this at the annual congress of the European College of Neuropsychopharmacology.

“Activation of the GABAB receptor by means of agonists or positive allosteric modulators of the GABAB receptor produces suppressive effects on alcohol intake, alcohol reinforcement, and motivation to seek for and consume alcohol,” said Dr. Giancarlo Colombo, of the Institute of Neuroscience at the Consiglio Nazionale delle Ricerche in Cagliari, Italy. “These data support the hypothesis of the involvement of the GABAB receptor in the neural substrate controlling alcohol drinking and seeking behaviors.”

In rodents, acutely or repeatedly administered baclofen suppressed several alcohol-related behaviors, including acquisition and maintenance of alcohol drinking behavior, relapselike drinking, bingelike drinking, and cannabinoid- or opioid-induced increases in alcohol intake under a variety of test conditions. Most of these findings were replicated by baclofen infusion into the ventral tegmental area of rats and mice, pointing to the likely involvement of the mesolimbic dopamine system, or the brain “reward” circuit, in alcohol dependence, Dr. Colombo explained.

Additionally, baclofen administration has been found to suppress the intensity of different signs of alcohol withdrawal syndrome, including anxiety-related behaviors, tremors and seizures, in rats made physically dependent on alcohol.

Preliminary clinical studies and accumulating case-reports have extended most of these findings to human alcoholics, as baclofen has been found to promote abstinence and suppress alcohol consumption, craving for alcohol, and severity of alcohol withdrawal symptoms, including delirium tremens, he said.

In case reports evaluating high doses of baclofen (75-270 mg/day), significant improvements have been observed in the achievement of complete abstinence, control over drinking, relapse prevention, and suppression of craving.

One physician who battled alcoholism, in fact, credits baclofen for his recovery in his book, “The End of My Addiction” (New York: Farrar, Straus and Giroux, 2008). The book cover asserts, “Olivier Ameisen was a renowned cardiologist until alcoholism took over his life. This is the story of how he cured himself.”

In open-label and double-blind clinical studies of low-to-moderate doses (30 mg/day), reductions have been observed in the number of daily drinks, days of heavy drinking, days of abstinence, and alcohol craving scores. However, in the most recent study (Alcohol Clin. Exp. Res. 2010 July 21 [doi: 10.1111/j.1530-0277.2010.01273.x]) baclofen showed no effective over placebo on alcohol drinking in alcohol-dependent patients treated for 12 weeks, he noted.

Possible reasons for the negative study might be that, compared with pivotal data from earlier Italian studies, the baseline number of drinks per day was lower, withdrawal symptoms were less severe, patients were recruited via U.S. newspaper ads rather than treatment centers, and patients had less severe dependence characteristics or different treatment goals.

Examining these discrepancies, Dr. Colombo speculated, “Baclofen may be more effective in the presence of more severe physical dependence.”

The newer positive allosteric modulators of the GABA receptor are showing promise for alcohol dependence in animal models, he added.

Dr. Colombo reported no potential conflicts of interest.

AMSTERDAM – The gamma-aminobutryric acid (GABA) receptor agonist baclofen, which is indicated for the treatment of spasticity, might represent a novel and effective drug treatment for alcohol dependence, according to an addiction specialist who presented evidence for this at the annual congress of the European College of Neuropsychopharmacology.

“Activation of the GABAB receptor by means of agonists or positive allosteric modulators of the GABAB receptor produces suppressive effects on alcohol intake, alcohol reinforcement, and motivation to seek for and consume alcohol,” said Dr. Giancarlo Colombo, of the Institute of Neuroscience at the Consiglio Nazionale delle Ricerche in Cagliari, Italy. “These data support the hypothesis of the involvement of the GABAB receptor in the neural substrate controlling alcohol drinking and seeking behaviors.”

In rodents, acutely or repeatedly administered baclofen suppressed several alcohol-related behaviors, including acquisition and maintenance of alcohol drinking behavior, relapselike drinking, bingelike drinking, and cannabinoid- or opioid-induced increases in alcohol intake under a variety of test conditions. Most of these findings were replicated by baclofen infusion into the ventral tegmental area of rats and mice, pointing to the likely involvement of the mesolimbic dopamine system, or the brain “reward” circuit, in alcohol dependence, Dr. Colombo explained.

Additionally, baclofen administration has been found to suppress the intensity of different signs of alcohol withdrawal syndrome, including anxiety-related behaviors, tremors and seizures, in rats made physically dependent on alcohol.

Preliminary clinical studies and accumulating case-reports have extended most of these findings to human alcoholics, as baclofen has been found to promote abstinence and suppress alcohol consumption, craving for alcohol, and severity of alcohol withdrawal symptoms, including delirium tremens, he said.

In case reports evaluating high doses of baclofen (75-270 mg/day), significant improvements have been observed in the achievement of complete abstinence, control over drinking, relapse prevention, and suppression of craving.

One physician who battled alcoholism, in fact, credits baclofen for his recovery in his book, “The End of My Addiction” (New York: Farrar, Straus and Giroux, 2008). The book cover asserts, “Olivier Ameisen was a renowned cardiologist until alcoholism took over his life. This is the story of how he cured himself.”

In open-label and double-blind clinical studies of low-to-moderate doses (30 mg/day), reductions have been observed in the number of daily drinks, days of heavy drinking, days of abstinence, and alcohol craving scores. However, in the most recent study (Alcohol Clin. Exp. Res. 2010 July 21 [doi: 10.1111/j.1530-0277.2010.01273.x]) baclofen showed no effective over placebo on alcohol drinking in alcohol-dependent patients treated for 12 weeks, he noted.

Possible reasons for the negative study might be that, compared with pivotal data from earlier Italian studies, the baseline number of drinks per day was lower, withdrawal symptoms were less severe, patients were recruited via U.S. newspaper ads rather than treatment centers, and patients had less severe dependence characteristics or different treatment goals.

Examining these discrepancies, Dr. Colombo speculated, “Baclofen may be more effective in the presence of more severe physical dependence.”

The newer positive allosteric modulators of the GABA receptor are showing promise for alcohol dependence in animal models, he added.

Dr. Colombo reported no potential conflicts of interest.

AMSTERDAM – The gamma-aminobutryric acid (GABA) receptor agonist baclofen, which is indicated for the treatment of spasticity, might represent a novel and effective drug treatment for alcohol dependence, according to an addiction specialist who presented evidence for this at the annual congress of the European College of Neuropsychopharmacology.

“Activation of the GABAB receptor by means of agonists or positive allosteric modulators of the GABAB receptor produces suppressive effects on alcohol intake, alcohol reinforcement, and motivation to seek for and consume alcohol,” said Dr. Giancarlo Colombo, of the Institute of Neuroscience at the Consiglio Nazionale delle Ricerche in Cagliari, Italy. “These data support the hypothesis of the involvement of the GABAB receptor in the neural substrate controlling alcohol drinking and seeking behaviors.”

In rodents, acutely or repeatedly administered baclofen suppressed several alcohol-related behaviors, including acquisition and maintenance of alcohol drinking behavior, relapselike drinking, bingelike drinking, and cannabinoid- or opioid-induced increases in alcohol intake under a variety of test conditions. Most of these findings were replicated by baclofen infusion into the ventral tegmental area of rats and mice, pointing to the likely involvement of the mesolimbic dopamine system, or the brain “reward” circuit, in alcohol dependence, Dr. Colombo explained.

Additionally, baclofen administration has been found to suppress the intensity of different signs of alcohol withdrawal syndrome, including anxiety-related behaviors, tremors and seizures, in rats made physically dependent on alcohol.

Preliminary clinical studies and accumulating case-reports have extended most of these findings to human alcoholics, as baclofen has been found to promote abstinence and suppress alcohol consumption, craving for alcohol, and severity of alcohol withdrawal symptoms, including delirium tremens, he said.

In case reports evaluating high doses of baclofen (75-270 mg/day), significant improvements have been observed in the achievement of complete abstinence, control over drinking, relapse prevention, and suppression of craving.

One physician who battled alcoholism, in fact, credits baclofen for his recovery in his book, “The End of My Addiction” (New York: Farrar, Straus and Giroux, 2008). The book cover asserts, “Olivier Ameisen was a renowned cardiologist until alcoholism took over his life. This is the story of how he cured himself.”

In open-label and double-blind clinical studies of low-to-moderate doses (30 mg/day), reductions have been observed in the number of daily drinks, days of heavy drinking, days of abstinence, and alcohol craving scores. However, in the most recent study (Alcohol Clin. Exp. Res. 2010 July 21 [doi: 10.1111/j.1530-0277.2010.01273.x]) baclofen showed no effective over placebo on alcohol drinking in alcohol-dependent patients treated for 12 weeks, he noted.

Possible reasons for the negative study might be that, compared with pivotal data from earlier Italian studies, the baseline number of drinks per day was lower, withdrawal symptoms were less severe, patients were recruited via U.S. newspaper ads rather than treatment centers, and patients had less severe dependence characteristics or different treatment goals.

Examining these discrepancies, Dr. Colombo speculated, “Baclofen may be more effective in the presence of more severe physical dependence.”

The newer positive allosteric modulators of the GABA receptor are showing promise for alcohol dependence in animal models, he added.

Dr. Colombo reported no potential conflicts of interest.