Naltrexone is a medication that has been used in the United States for the treatment of alcoholism since its 1994 approval by the federal Food and Drug Administration. Many of the original studies of naltrexone’s effectiveness, however, examined alcohol-dependent patients with an “Anglo-Saxon” or “Scandinavian drinking pattern,” that is, greater drinking on holidays and weekends. Conversely, individuals with a “Mediterranean drinking pattern” tend to regularly consume alcohol during the week, particularly with meals. A study in the September issue of Alcoholism: Clinical & Experimental Research is among the first to examine the effectiveness and safety of naltrexone for the treatment of alcoholism among Spanish patients with a Mediterranean drinking pattern.
“Years ago,” said José Guardia, a consultant at the Hospital de la Santa Creu i Sant Pau in Barcelona, Spain and lead author of the study, “there was a clear difference between drinking patterns in the northern and southern countries of Europe. The Anglo-Saxon/Scandinavian tendency was to drink more on holidays and weekends. In France, Italy, Spain and other Mediterranean countries, wine was usually consumed with meals. However, when everyday consumption becomes heavy, and after a long period of time, severe withdrawal and organic consequences of chronic alcohol toxicity are probable. We wanted to see if there would be differences in using naltrexone for the treatment of alcohol dependency in this population.”
Drugs can have agonist and/or antagonist properties. Agonists activate a receptor to achieve their effect. Antagonists block the receptor from being activated by an endogenous (produced within the organism) or exogenous (produced outside the organism) chemical. Naltrexone acts as an opioid antagonist within the opioid neurotransmitter system, which is a part of the brain’s reward system. When opioids are stimulated, levels of the dopamine neurotransmitter are increased, leading to the “high” that is associated with a variety of drugs. Naltrexone “blocks” the opioid receptor from being activated. It was first developed in the 1970s to block heroin from activating the receptors for opiates, later becoming approved for the treatment of heroin addiction in the mid-1980s. In the late 1980s, researchers began to suspect it might have uses for the treatment of alcohol addiction.
For the Guardia study, subjects were 202 alcohol-dependent patients (151 males, 51 females), 18 to 60 years of age, who were seeking outpatient treatment from seven different treatment centers in Spain. Patients were randomly assigned to 12 weeks of treatment with either 50 mg/day of naltrexone (n=101) or an identical-looking placebo (n=101). Patient treatment also included a “psycho-social intervention,” consisting of a weekly session of supportive group therapy, a weekly visit with the study physician, and a nurse intervention three times a week. Following treatment, researchers evaluated the relapse rate, alcohol- consumption levels, craving, adverse effects, changes in the biochemical markers of heavy drinking, and possible toxicity among the final tally of 192 patients considered eligible for evaluation.
Of the naltrexone-treated subjects, only 7.9 percent (n=8) relapsed to heavy drinking. (Heavy drinking was defined as more than five drinks per day for men, more than four drinks per day for women, or more than five drinking days per week for both genders.) Of the placebo-treated subjects, 18.8 percent (n=19) relapsed to heavy drinking. The adverse effects known to be associated with naltrexone use (nausea, headache, abdominal discomfort, sleepiness) were low among those treated, confirming previous studies of naltrexone’s safety and tolerability.
“The most significant finding of our study was that naltrexone-treated alcohol-dependent subjects showed a reduced relapse rate to heavy drinking,” said Guardia, “in comparison with those patients treated with a placebo. These results demonstrate the synergistic effects of combining pharmacotherapy with psycho-social intervention. We know that alcoholism is a recoverable disease. These results show that when alcohol-dependent patients get the appropriate psycho-social intervention plus pharmacotherapy for a suitable amount of time, they can overcome this addictive disease.”
“These results open up the possibility for European alcohol-dependent patients to receive treatment with naltrexone,” said José Pérez de los Cobos, a psychiatrist with the Addictive Behavior Unit at the Hospital de la Santa Creu i Sant Pau. In fact, since this study was conducted, naltrexone has been authorized for the treatment of alcoholism in Spain. “Furthermore,” he added, “once we understand the effectiveness of naltrexone, we can go on to explore its limitations. That way, future research can examine how combining naltrexone with other medications, and even more effective psycho-social interventions, can treat alcoholism.”
Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.
Articles were written based on the following published research:
Guardia, J., Caso, C., Arias, F., Gual, A., Sanahuja, J., Ramirez, M., Mengual, I., Gonzalvo, B., Segura, L., Trujols, J., Casas, M. (September, 2002). A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol-dependence disorder. Results from a multicenter clinical trial. Alcoholism: Clinical & Experimental Research, 26(9), 1381-1387.