Substance Abuse Treatment Modalities: Literature Review

Anti-Alcohol Drugs

Two anti-alcohol drugs are available for use in Canada: Antabuse® (disulfiram) and Temposil® (citrated calcium carbimide). These drugs are also sometimes called “alcohol sensitizing agents,” or “antidipsotropic medications.” When ingested prior to drinking, both medications are thought to prevent drinking by creating the threat that an aversive reaction will occur when alcohol is consumed. This reaction occurs because the medications interfere with the normal metabolism of alcohol. Specifically, they inhibit the production of a liver enzyme that breaks down the ethanol by–product of acetaldehyde. As a result, when alcohol is consumed there is a build–up of acetaldehyde in the bloodstream, and this produces an aversive reaction similar to that of a severe allergy (e.g., flushing, rapid or irregular heartbeat, dizziness, nausea, vomiting, difficulty breathing, headache).

These medications do not produce an aversive effect until a critical level of the medication has been achieved in the body. For Antabuse® a sufficient level is usually achieved within four to seven days of beginning to take the medication. Temposil® has a shorter half life than Antabuse and usually reaches a sufficient level within 12 to 24 hours of starting use. Because these medications stay in the body for an extended period after consumption ends, an aversive reaction will still be experienced for some time after use of the anti-alcohol medication has been discontinued. For Antabuse® this is typically four to seven days, whereas for Temposil® the reaction typically will not occur after about one or two days.

Most of the research on anti-alcohol medications has concerned Antabuse®. Since Temposil® works in a similar fashion except for having a shorter duration of action, much of the Antabuse® research should be directly applicable to Temposil® except for factors related to temporal differences in action between the two medications. Antabuse® has been used clinically since 1948, but sound clinical trials of its efficacy have only been conducted recently. Early randomized controlled trials with severe alcoholics found that Antabuse® was not effective, with the possible exception of individuals whose taking of the medication was witnessed. The most definitive studies of Antabuse® have been conducted by Fuller and his colleagues in Veterans Administration programs in the U.S. Antabuse® typically is used as only one element of a treatment program. In a 1979 trial Antabuse® was either added or not added to a multi-modal treatment program conducted with married males. Overall the results were disappointing, in that the patients on Antabuse® did not maintain continuous abstinence significantly better than patients who did not receive Antabuse®. This advantage probably had little to do with the capacity of Antabuse® to produce an aversive reaction, however, since individuals receiving only 1 mg of Antabuse® did as well as those receiving the regular dose of 250 mg. A more recent multi-centre trial conducted by Fuller et al (1986) replicated the earlier study but used a much larger sample. Again it was found that there was no significant difference in outcomes for men who did or did not receive Antabuse®. Importantly, overall only 20% of the patients were judged to be compliant with the Antabuse® treatment. This identifies the key drawback of anti-alcohol drugs - that most patients discontinue their use. A subset of individuals who tended to use the medication willingly and as prescribed, and who were somewhat older and more socially stable than the others tended to have less serious relapses if they drank.

Several other studies have either found no added benefit to the use of Antabuse®, or positive findings have been explainable in terms of other factors such as motivation and compliance (Institute of Medicine, 1989). Women typically have not been included in these trials.

Relevant to an offender population, monitored use of Antabuse® has been found to have some effectiveness, although randomized controlled trials have not been conducted using these procedures. Monitoring is a practical issue that requires having available a party (either at a treatment program or in the home or community) to witness the ingestion of the medication, and in most cases having some leverage to compel the patient to take Antabuse® under those circumstances. This could involve monitoring by a significant other (e.g., Azrin et al., 1989) or, for example, taking Antabuse® in front of treatment program staff in order to receive methadone (for heroin abusers who also abuse alcohol; see Bigelow et al., 1980).

Over the years work has occasionally been directed at developing a longer lasting form of disulfiram, such as implants or skin patches. Such procedures have been complicated by poor regulation of dose (i.e., often an implant would not yield sufficient disulfiram in the bloodstream to yield a disulfiram-ethanol reaction if alcohol was consumed), wound infections, and findings that drinking by patients who received the implants did not differ significantly from that of patients who did not receive the implants.

In summary, under certain conditions anti-alcohol medications have clinical utility. These circumstances are primarily either when patients are socially stable, well motivated and highly compliant (and therefore probably a good candidate for any approach); or when medication ingestion can be monitored. The latter condition is probably most relevant for the use of anti-alcohol medication in working with offenders. For well-motivated patients it is thought that the effectiveness of anti-alcohol medications lies in the belief that one has ingested the medication. This is because patients who do well with the medication typically do not drink and therefore never experience an aversive reaction. Friedman and Fulop (1988) reported that treatment philosophy and administrative attitudes were more important determinants of Institute of Medicine. (1989)disulfiram use than were patient characteristics or treatment settings. Finally, disulfiram can occasionally have serious side effects. Citrated calcium carbimide has fewer side effects, but in each case the medication must be prescribed by a physician (a limitation for some programs) and the potential benefits of the medication must be weighed against the potential side effects.

References for Anti-Alcohol Drugs:

Azrin, N. H., Sisson, R. W., Meyers, R., & Godley, M. (1982), “Alcoholism treatment by disulfiram and community reinforcement therapy”, Journal of Behavior Therapy and Experimental Psychiatry, 13, 105-112.

Bigelow, G., Stitzer, M., Lawrence, C., Krasnegor, N., D'Lugoff, B., & Hawthorne, J. (1980), “Narcotics addiction treatment: Behavioral methods concurrent with methadone maintenance”, International Journal of the Addictions, 15, 427-437.

Fuller, R. K. (1989), “Antidipsotropic medications”, In: R. K. Hester & W.R. Miller, Eds., Handbook of Alcoholism Treatment Approaches: Effective alternatives. New York: Pergamon Press, pp. 117-127.

Institute of Medicine (1990), Broadening the base of treatment for alcohol problems, Washington, DC: National Academy Press.

Institute of Medicine (1989), Prevention and treatment of alcohol problems: Research opportunities, Washington, DC: National Academy Press.

National Institute on Alcohol Abuse and Alcoholism (1993), Eighth Special Report to the U.S. Congress on Alcohol and Health (U.S. Department of Health and Human Services). NIH Publication No. 94-3699. Washington, DC: U.S. Government Printing Office.

Saunders, J. B. (1989), “The efficacy of treatment for drinking problems”, International Review of Psychiatry, 1, 121-138.