Study published in JAMA reveals a new weapon against alcoholism
The drug ondansetron, currently used to treat nausea and vomiting in chemotherapy patients, is highly effective in treating alcoholics with neurochemical abnormalities, according to Health Science Center researchers. The scientists, led by Dr. Bankole A. Johnson, share the exciting findings from five years of study in the Aug. 23 issue of the Journal of the American Medical Association (JAMA).
A 1-, 4- or 16-microgram per kilogram dose of ondansetron, taken twice a day by mouth for 11 weeks, resulted in less drinking and more days of abstinence among study participants taking the active drug as opposed to a placebo (inactive agent).
Although ondansetron (trade name Zofran®, Glaxo Wellcome) would need to be reformulated for this application, the finding may lead to the development of new therapeutic agents for treating the biological form of alcoholism, says Dr. Johnson, the William and Marguerite S. Wurzbach Distinguished Professor in the Departments of Psychiatry and Pharmacology at UTHSC, deputy chairman for research in the Department of Psychiatry and chief of its Alcohol and Drug Addiction Division.
The study enrolled 321 patients in San Antonio and in Houston, where Dr. Johnson and his team conducted research from 1993 to 1998. The scientists formed the hypothesis that individuals classified as "early onset alcoholics" have abnormalities of serotonin, a neurotransmitter or "chemical messenger" in the brain.
"For decades it has been known that, for some, alcoholism runs in the family, and that certain brain abnormalities may be transmitted," Dr. Johnson says. "Typically, early onset alcoholics begin drinking in their youth, develop anti-social problems and are the hardest to treat.
"Based on the hypothesis that these alcoholics have abnormalities of the serotonergic system, we showed that a specific serotonergic medication (ondansetron) resulted in an abstinence rate of about 70 percent in biological alcoholics who received the therapy vs. 50 percent in a comparable group who received placebo."
Study participants were randomized to receive either one of three medication doses or the placebo. Participants also were enrolled in weekly psychotherapy and measures designed to evaluate physical, social and mental well-being, and drinking. Says Dr. Johnson: "Ondansetron significantly reduced the alcohol consumption of these biological alcoholics, presumably by correcting underlying disequilibrium in the serotonergic brain system." This study was funded by a grant from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Dr. Johnson’s team also received both a five-year, $3.2 million NIAAA competitive renewal grant that started July 1 and an award from the Texas Commission on Alcohol and Drug Abuse to further investigate the medication’s effectiveness.
"This seminal finding will enable us to determine whether we can work out a neurochemical abnormality that ondansetron corrects," he says. "Our goal is to more easily target alcoholics who would respond best to ondansetron and to develop even better agents. In the future, we expect to be able to use molecular genetics to identify those at greatest risk for this severe form of alcoholism even before they get it. And if they get it, we should be able to provide them with a highly effective therapy." These findings may provide powerful treatment options for an important subgroup of the 14 million Americans—1 in every 13 adults—who abuse alcohol or are alcoholics.
NIAAA Director Dr. Enoch Gordis comments: "Innovative pharmacologic treatments, developed from neuroscience research and used together with proven behavioral treatments, hold considerable promise to improve alcoholism treatment outcome. These positive early results on ondansetron require replication but provide another reason for hope that alcoholism ultimately will yield to treatments that precisely target its mechanisms."
"New therapy directed specifically at early onset alcoholics is exciting for several reasons," says Dr. R. Adron Harris, the M. June and J. Virgil Waggoner Professor at U.T. Austin and director of the Waggoner Center for Alcohol and Addiction Research. "The public health implication is that it provides treatment for those who have the most to gain from stopping their alcohol abuse.
"In terms of years of life lost and other measures, this is clearly a group to try to get into treatment. It is also a group that has difficulty maintaining abstinence, and it will be of great interest to see if effects of ondansetron are long lasting."
Ondansetron is the first treatment specifically targeted to a subtype of alcoholism, and it is especially noteworthy that Dr. Johnson’s team predicted the effect, based on genetic differences in serotonin systems among individuals.
"This makes the dream of effective matching of treatment to the alcoholic patient closer to a reality," Dr. Harris says. "It also raises the possibility of using a genetic test to predict which patients will respond to ondansetron. This would give the treatment of alcoholism a real biological basis, as is the case for some other diseases."
Dr. Harris noted that few drug therapies are available for alcoholism. "This is in contrast to other diseases, such as hypertension, for which there are many effective drugs and the best agent for a particular patient can be chosen. Effective pharmacotherapy of alcoholism is finally, albeit slowly, becoming a reality."
Says Dr. Pedro Ruiz, professor and vice chairman of clinical affairs, Department of Psychiatry, at the U.T. Houston Health Science Center and medical director of the U. T. Mental Sciences Institute: "Dr. Bankole A. Johnson’s research efforts on the impact of ondansetron on early onset alcoholics, which began in Houston and were completed in San Antonio, represent a major breakthrough. Without question, these findings offer a good outlook for this group of alcoholics, who start to drink early in life and depict major problems in their personality profiles."
Dr. Johnson earned his medical degree from Glasgow University in Scotland and conducted his doctoral studies at Oxford University. He joined the Health Science Center in 1998.
The following researchers collaborated on the study. From the UTHSC: Drs. John Roache, Martin Javors, Thomas Prihoda, Patrick Bordnick, Nassima Ait-Daoud and Julie Hensler. From the University of Maryland: Dr. Carlo DiClemente. From the Washington University School of Medicine: Dr. C. Robert Cloninger.