April 8, 2005

Alcohol drug’s new dose shows promise

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Mark Anderson, M.D., Ph.D., Roger Colbran, Ph.D., and Rong Zhang, M.D./Ph.D.
photo by Dana Johnson

Alcohol drug’s new dose shows promise

A once-a-month injection of an FDA-approved medication used for treating alcohol dependence may improve long-term outcomes, according to a study published in the April 6 issue of the Journal of the American Medical Association.

The drug, naltrexone, has been proven effective in the treatment of alcohol dependence, but it is often difficult for patients to adhere to daily oral doses, says Peter R. Martin, M.D., professor of Psychiatry and Pharmacology and director of the Division of Addiction Psychiatry.

The study tested the efficacy and safety of a new formulation, which releases the naltrexone for one month following a single injection.

Vanderbilt University Medical Center was part of the six-month, randomized, double-blind, placebo-controlled trial, which was conducted between February 2002 and September 2003 at 24 U.S. public hospitals, private and Veteran Administration clinics and tertiary care medical centers. Martin and David D. Weinstein, M.D., assistant professor of Psychiatry, were in charge of the Vanderbilt portion of the study of 31 patients. The national trial included 624 adult patients who received at least one injection.

Alcohol dependence is a major public health problem and is the fourth leading cause of disability in the world, according to the JAMA article. Alcohol dependence is present in approximately 4 percent of the U.S. adult population and may contribute to more than 100,000 preventable deaths per year, the study says.

The researchers, led by principal investigator James C. Garbutt, M.D., of the University of North Carolina at Chapel Hill, found that compared with placebo, 380 mg. of long-acting naltrexone resulted in a 25 percent decrease in the event rate of heavy drinking days and 190 mg. of naltrexone resulted in a 17 percent decrease. The study also showed that men and those who abstained from alcohol use both exhibited greater treatment effects.

Martin said that patients often turn away from treatment because they are told to abstain from drinking alcohol. “Clearly, that's the best approach, but people like gray areas, not black and white. In this study, we encouraged our patients to be abstinent, but told them if they have to drink, it's ok, we'd still take care of them.” There were still a number of patients who completely abstained from drinking alcohol.

The study addressed risk reduction, and monitored the amount that each participant had to drink while enrolled in the study, Martin said. “You can look at alcoholism like high blood pressure. You might not be able to get a person's blood pressure down to 110/70, but it's better to have it a little higher than normal than a lot higher than normal. In general, the less the offending agent, the less the complications.”

Treating alcoholism involves much more than just encouraging abstinence, Martin said. There are a wealth of problems associated with alcohol dependence — difficulties with relationships, employment, and in living a fulfilling life.

“The fact is that in this study, the alcohol consumption in our patients was significantly reduced, and there were also some benefits in terms of their capacity to engage in treatment and go on with their lives. These were all positive things.”

Martin said that one of the complications of alcoholism is the lack of compliance with treatment.

“In general, many of the issues that make a person consume alcohol over and over are the same issues that make it difficult for them to adhere to physician advice and recommendations. So the thought was, what if we take a medicine that has been shown in a number of clinical trails to have some benefit in reducing alcohol consumption and deliver it using a vehicle that allows a monthly injection and thereby the patient doesn't have to comply.”

Naltrexone is a medication that blocks the effects of drugs known as opioids (a class that includes morphine, heroin or codeine). It competes with these drugs for opioid receptors in the brain. It was originally used to treat dependence on opioid drugs but has recently been approved by the FDA as treatment for alcoholism. In clinical trials evaluating the effectiveness of naltrexone, patients who received it were twice as successful in remaining abstinent and in avoiding relapse as patients who received placebo — an inactive pill. While the precise mechanism of action for naltrexone's effect is unknown, reports from successfully treated patients suggest three kinds of effects. First, naltrexone can reduce craving. Second, naltrexone helps patients remain abstinent. Third, naltrexone can interfere with the tendency to want to drink more if a recovering patient slips and has a drink.

Martin said that more study will be needed to find out why men seem to respond better to this treatment. More investigation is also needed into the interaction of psychosocial interventions and medications since there was a substantial reduction in the consumption of alcohol in those who received placebos as well as those who received the active medication.

Martin said the reduction in those with the active medication was significantly greater than those who received the placebo.