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ShareNovember 12, 2010 (Denver, Colorado) — A small study in Minnesota has replicated findings from Italy indicating that off-label use of the gamma-aminobutyric acid–derivative baclofen is effective in treating symptoms of alcohol withdrawal syndrome (AWS). The drug has been approved for treating spasticity.The study was presented as a poster here at the American Public Health Association 138th Annual Meeting by Charles E. Gessert, MD, MPH, from the Essentia Institute of Rural Health, in Duluth, Minnesota. It has been accepted for publication.Dr. Gessert and colleagues were particularly concerned with alcohol-dependent patients who were injured in an accident and who began to manifest symptoms of AWS while hospitalized. He explained to Medscape Medical News: “Alcohol blocks neurotransmission[, and absent the alcohol,] the whole nervous system is hyperexcited. You get all of the symptoms of alcohol withdrawal.”
The most common treatment is benzodiazepine, which blocks neurotransmission at the same point as alcohol. However, the high doses used carry risks for morbidity such as respiratory suppression and prolonged hospitalization. “Baclofen blocks neurotransmission [and] the symptoms of alcohol withdrawal,” and acts at a different point in the transmission process, Dr. Gessert said.
The prospective, double-blind, randomized, placebo-controlled study involved 79 inpatients at risk for AWS. Of these, 44 developed symptoms of AWS and were randomly assigned to receive baclofen 10 mg or placebo 3 times per day. In all, 31 patients completed the 72 hours of observation and assessment required by the study and were available for evaluation.
When the study was unblinded, the researchers found that 1/18 patients in the baclofen group and 7/13 patients in the placebo group (P = .004) required a high dose of benzodiazepines (20 mg or more of lorazepam) during the 72-hour period to control symptoms of AWS.
Baclofen was safe and well tolerated, which came as no surprise, as it has been used for treating chronic conditions for years. It does potentially have some of the same risks as benzodiazepine when given at high doses, but this study used low doses, for a short period of time. The literature suggests that there is little risk for physical dependency.
The principle investigator of the study, Jeffrey E. Lyon, MD, is planning a follow-on study that will enroll patients at risk for AWS and not wait for them to develop symptoms before administering the drug. “We want to see if we can prevent symptoms from developing in the first place,” said Dr. Gessert.
He foresees possible broader use as part of a program for alcohol cessation, “particularly for the alcoholic whose life hasn’t completely deteriorated and [who] still has some intact social support.” However, it may prove difficult to conduct such studies and gain the label indication for a drug that is available as a generic.
“Conducting this study has given me new respect for the compelling physiologic nature of alcohol dependency. It means that when people are being withdrawn from alcohol as a life choice, they need both physiological and psychological support,” said Dr. Gessert.
Lorenzo Leggio, MD, has studied baclofen extensively, first in Italy and now at the Brown University Center for Alcohol and Addiction Studies, in Providence, Rhode Island. He called the trial “really interesting,” in that it used a “gold standard trial design” and evaluation methodologies. Most notable was the fact that patients were hospitalized, which is cost-prohibitive for most studies.
This study confirms what has been seen in other studies with similar but not identical designs. Still, “it is too early to advise physicians to use baclofen for treating AWS,” Dr. Leggio said. Industry is not interested in funding research on a generic drug, so support must come from the National Institutes of Health and from other foundations, he noted.
Dr. Leggio said baclofen is very safe to use in patients with liver disease because it is primarily metabolized through the kidneys, unlike alternative drugs for alcohol dependency that are metabolized in the liver and are contraindicated for patients with cirrhosis.
Dr. Gessert and Dr. Leggio have disclosed no relevant financial relationships.
American Public Health Association 138th Annual Meeting: Abstract 4225.0-4. Presented November 9, 2010.