Current Pharmacological Treatment Available for Alcohol Abuse
In 1999, The University of North Carolina at Chapel Hill published Pharmacotherapy for Alcohol Dependence*. Excerpts from this important document are included to provide a brief overview of the available pharmacological treatment for alcohol addiction.
Considerable uncertainty surrounds the question of how best to maintain abstinence in patients who are in remission. Some of this uncertainty stems from a debate between those who advocate a "drug-free" 12-step approach that does not incorporate use of any pharmacotherapies and those who, while accepting the great value of the 12-step approach, hold that use of appropriate, non-addictive medications may be an important step toward improved outcomes. In addition, controversy and uncertainty remain about the advantages and drawbacks of those types of medications. Disulfiram ("Antabuse"®), for example, is not effective for many patients; they may consume alcohol while on disulfiram, or more likely, stop taking the medication entirely. Moreover, clinicians are not sure of the pharmacologic or physiologic mechanisms (or the potential side effects) of certain other agents. This hampers their ability to judge whether their patients are appropriate candidates for such therapy.
The pharmacotherapy of alcoholism attempts to accomplish one or more of four goals:
- Treat the core dependence syndrome including craving, preoccupation, and loss of control.
- Enhance abstinence and minimize relapse by the threat of or the development of aversive consequences (or both) in response to alcohol consumption.
- Treat co morbid disorders that increase the likelihood of alcohol use.
- Treat the consequences of alcohol use such as protracted abstinence symptoms, cognitive impairment, and liver problems.
Medications that have been used in the treatment of alcoholism vary widely in their mechanisms of action. A brief summary follows of the known or presumed mechanisms of action of the major drugs considered in this report.
Disulfiram is used to reinforce the patient's desire to stop drinking by providing a psychological deterrent to consuming alcohol that is then reinforced by an unpleasant response should alcohol be consumed. Disulfiram has been in use for the treatment of alcoholism for close to 50 years.
Naltrexone, an opiate antagonist, received FDA approval in December 1994 and became the first drug to be approved for the treatment of alcoholism since disulfiram's approval. Naltrexone is believed to reduce the craving for alcohol, the reward produced by alcohol, the intensity of intoxication, or all three of these alcohol outcomes (Hyytia & Sinclair, 1993; Volpicelli, Watson, King, et al., 1995; O'Malley, Jaffe, Rode, et al., 1996; Spanagel & Zieglgansberger, 1997; Wilcox & McMillen, 1998).
Acamprosate, calcium acetyl homotaurinate, has been widely studied in European populations with alcoholism, but its mechanisms of action have not yet been clarified.
The involvement of the brain's serotonergic system in alcohol intake is well documented. Manipulations leading to decreased serotonin function seem to increase ethanol intake (for review see LeMarquand, Pihl, and Benkelfat, 1994). Low levels of serotonin are thought to result in increased impulsiveness and craving components that can contribute to the development of alcoholism.
Lithium has been used successfully in treating patients with affective disorders (Coppen, Noguera, Baily, et al., 1971), and it was initially thought to be beneficial for the treatment of alcoholics who can exhibit cyclic mood swings and depression. Early publications suggested that the therapeutic effect of lithium derived from the stabilization of associated affective disorders, although the evidence to support this view was largely indirect. Judd, Hubbard, Huey, et al. (1977) and Judd and Huey (1984) found that lithium attenuates the subjective sensation of alcohol intoxication, including self-rating report of the desire to continue drinking after the ethanol challenge. In addition, Hirschowitz, Hitzemann, Kovasznay, et al. (1989) showed that lithium could produce a decrease in ethanol-induced intoxication, as measured by cognitive tests.