Alcoholism: Newer drugs advancing treatment goals
Federal study analyzes five treatments
Pharmacotherapies for the treatment of alcoholism continue to receive the lion’s share of research and funding. According to the American Society of Addiction Medicine, 10% of adult Americans are affected by alcoholism, and 100,000 die each year from its effects, costing the country $166 billion a year.
This June, the federal Agency for Health Care Policy and Research (AHCPR) published an updated analysis of old and new drugs used to fight the condition, which the agency stresses should clearly be termed a disease.
The paper, which is titled Pharmacotherapy for Alcohol Dependence, analyzes five drug or drug-class treatments aimed at reducing relapses, reducing cravings, or interfering with the brain’s pleasure centers, and includes information on disulfiram, lithium, and serotonergic agents (SSRIs, ondan setron, buspirone) as the more traditional therapies, along with two newer drugs, naltrexone and acamprosate, which are generating interest through positive early results. But questions such as mechanisms of action with the new drugs and overall drug regimens still need to be studied.
Treating alcoholism is a package deal
Says Ray Litten, PhD, program director at the National Institute of Alcohol Abuse and Alcohol ism, "Alcoholism is a complicated disease. Even now, there is no magic bullet for it. The best strategy may be to use a packaged treatment program, combining psychosocial therapies and medication."
For years, the only medication available to treat alcoholism was disulfiram, marketed as Antabuse. Essentially, it works by making people sick if they drink alcohol. Researchers say side effects of the drug, such as drowsiness and liver complications, also have contributed to its recent falling from favor as a frontline treatment.
Researchers also say it needs to be used as part of a packaged treatment program, rather than on its own. Finally, the AHCPR study notes that while there is evidence the drug reduces the number of "drinking days," there is little evidence it enhances abstinence or reduces cravings.
A more promising adjunct treatment for alcoholism is naltrexone. The FDA approved it for treating alcohol dependence in 1994, after two efficacy studies showed it could significantly reduce drinking compared to a placebo. But the drug’s exact mechanisms are still something of a mystery.
"We aren’t quite sure how it works, although it does seem to reduce the craving for alcohol," says Litten. "We do find that if people slip and take a drink, they may not want to continue. As scientists, we are not even sure exactly what craving is, biologically speaking."
That in itself it not necessarily bad, he stresses, adding that the more researchers learn about how the brain is affected by alcohol, the more strategies will come into focus for the development of pharmacotherapies.
Naltrexone receives good marks across the board in the AHCPR study, which deems the trials of its effectiveness "of generally good quality," and states there is good evidence the drug reduces relapse and craving and reduces the number of drinking days.
Promising weapon against relapse
A newer drug, acamprostate, also is receiving high marks for certain aspects of therapy, as researchers stress that matching specific drugs to specific patient maladies is preferred at this stage in the research. After drugs are targeted, combinations should be undertaken to encompass more areas of abuse and dependence.
Acamprosate is primarily being researched for its ability to prevent relapse. It is approved for use in 29 European countries. An investigational new drug application has been filed with the FDA by the drug’s manufacturer, Merck, while Phase III trials in 21 U.S. centers continue. In the United States, Merck plans to market the drug under the name Campral. Litten says FDA approval for acamprosate could come in two years.
A different mechanism than naltrexone
Scientists believe the drug acts on glutamate receptors, but Litten says they don’t exactly know how. They do know the drug does not act in the same exact way as naltrexone. One theory is that naltrexone blocks the positive reinforcing effects, or the high one assumes from alcohol, rendering its abuse moot, while acamprosate blocks the negative or despondency effects of alcohol, making it an alcohol substitute for frontline abuse treatment.
"Alcohol causes changes within neurons. If those changes can be analyzed, it may be possible to develop intercellular therapies. So these are exciting possibilities," says Litten.
The AHCPR study notes good evidence in the drug’s ability to enhance abstinence, but notes "minimal evidence" of its ability to avert relapse. In its evaluation of serotonergic agents, the study states that while there are several trials involving alcoholics "without comorbid mood or anxiety disorders . . . there is minimal evidence on the efficacy of serotonergic agents for treatment of the core symptoms of alcohol dependence."
Therefore, the study concludes, the agents are best used to treat "alcohol dependent symptoms" in patients with mood or anxiety disorders, which themselves call for drugs like SSRIs, though even in these cases, the study says data are limited.
Finally, the use of lithium is downplayed as an effective tool, based on limited studies of alcoholics not suffering from comorbid mood disorders, for which lithium is more commonly used. And that leaves little evidence of the drug’s efficacy on the core symptoms of alcohol dependence.
The study concludes, "Recent reports documenting that naltroxene and acamprosate are more effective than placebo in the treatment of alcoholism justify clinical interest in use of these medications for alcohol-dependent patients.
"Use of disulfiram is widespread but less clearly supported by the clinical trial evidence; however, targeted studies on supervised administration of disulfiram may be warranted. Use of existing serotonergic agents or lithium for patients with primary alcohol dependence does not appear to be supported by the efficacy data available at this time; these medications may still have a positive effect in patients with coexisting psychiatric disorders."
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