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The unhooked.com science section contains selected educational readings from the scientific and popular literature about alcoholism, addiction, and recovery. The views expressed in the articles are those of their authors and not necessarily those of the science pagemaster or the webmaster or of the person who suggested the article to the list. This material is made available solely for the nonprofit educational use of unhooked.com readers as an aid in their personal recovery, and no other use is authorized or intended. Click here for the current Science Section reading list.
By: Charles P. O'Brien, MD, PhD; A. Thomas McLellan, PhD; University of Pennsylvania, Philadelphia
Patients dependent on alcohol or other drugs are found in the practices of almost all physicians. Responsible physicians should be able to recognize substance abuse at an early stage and should be knowledgeable about referring patients to effective treatments. In practice, however, most alcohol and other drug dependence has gone unrecognized by physicians. Even when patients are suffering from obvious medical and social complications of alcoholism, only a minority are referred for treatment. This is partly because of stigma and poor attitudes about addicted patients on the part of physicians--but also because of a lack of knowledge about where to refer for treatment and a general skepticism regarding the effectiveness of any treatment. Recent research findings provide additional data indicating that substance abuse treatments can have enduring benefits and that physicians can have an important role in those treatments. Three sets of findings from the field of alcohol treatment research illustrate this point.
An important development has been the emergence of effective medications for the treatment of alcohol addiction. Until 1995 there were no Food and Drug Administration-approved medications for the treatment of alcoholism other than disulfiram (Antabuse). There were specific problems with the adverse effects associated with disulfiram and controversy regarding the use of any medication. Many believed "you can't treat a drug/ alcohol problem with a drug." With funding from the Department of Veterans Affairs, the National Institute on Drug Abuse, and the National Institute on Alcohol Abuse and Alcoholism, I new medication has been approved for use in the treatment of alcohol dependence and at least I other promising medication is undergoing trials.
The most recently approved of these medications is naltrexone, an opiate antagonist used successfully for years in the treatment of opiate dependence. Research with animal models on the effects of alcohol showed that among its many effects is the ability to release endogenous opioids, such as endorphins and enkephalins, in the central nervous system1 Some alcoholics (possibly those with more genetically influenced alcoholism) seem to be exquisitely sensitive to this effect and report an unusual kind of high or euphoria when they drink alcohol.2 The endogenous opioid activation results in release of dopamine in reward systems of the brain. Opiate receptor antagonists such as naltrexone block the endogenous opioid circuit, thus blocking dopamine-mediated euphoria? In animal models that use rodents and monkeys, preference for alcohol was markedly decreased by the administration of naltrexone.4 On the basis of these animal studies, naltrexone was given in double-blind, placebo-controlled trials to alcoholics in outpatient rehabilitation programs. The first study, completed by Volpicelli and colleagues at the Philadelphia Veterans Affairs Medical Center, was later confirmed by O'Malley and colleagues at Yale.7 Subsequently, other studies have produced positive results in alcoholics with the use of naltrexone or another opiate antagonist, nalmafene.8
It is important to note that in all of the studies so far, naltrexone has been prescribed in the context of supportive outpatient counseling and rehabilitation services. Standard counseling and rehabilitation services alone have been shown to be effective, reducing alcohol use and its associated problems by at least 50% for as long as a year after treatment. Studies done thus far show that naltrexone added to this standard care reduces relapse rates and prevents many of those who do relapse from a rapid return to full dependence. More controlled clinical trials are under way to answer questions concerning which patients may be most likely to respond to naltrexone and how long treatment should continue.
A second medication, acamprosate, is undergoing study in clinical trials in the United States and has already been approved in several European countries. The mechanisms of action for acamprosate are less well understood. It also acts on brain reward systems, blocking some of the y-aminobutyric acid-mediated reinforcing effects of alcohol. Recent European studies indicate that significantly more patients remained abstinent when prescribed acamprosate than when given placebo.
Availability of these medications alone is not enough to ensure their appropriate use. In parallel with the discovery and approval of these medications, the American Society of Addiction Medicine, the American Academy of Addiction Psychiatry, and other professional organizations have developed national education and training programs for physicians. More drug development research and physician training are needed, but these developments offer new options.
Recent findings also suggest that there are at least 3 effective behavioral or psychosocial treatments for alcohol dependence. A major multisite trial entitled "Project MATCH"11 studied 952 alcohol-dependent patients randomly assigned to one of three 12-week programs: cognitive behavioral coping skills therapy, motivational enhancement therapy, or 12-step facilitation therapy (therapy designed to prepare and encourage patients to affiliate with Alcoholics Anonymous). About two thirds of the treatment sessions in all conditions were attended, and 90% of the patients were interviewed at the 1-year posttreatment assessment. All 3 therapies produced excellent and approximately equal results, with patients in all groups abstinent for approximately 80% of the posttreatment period. If 3 consecutive drinking days are used as a criterion for relapse, then less than 40% of these outpatients relapsed during the 12 months after their initial treatment. There was little indication that any I "type" of alcohol-dependent patient did significantly better in any of the 3 forms of treatment.
The generalizability of results from these behavioral interventions is still in question, since patients with concurrent drug dependence or serious psychiatric problems were eliminated and the posttreatment period included multiple sessions of research monitoring, which may have partially accounted for the effects seen. Also, the newer medications were not available at the time this trial was initiated, so it is unknown what the results might have been with medication. At the same time, the positive findings from these behavioral intervention trials offer physicians and their patients effective alternatives in the treatment of alcohol dependence.
For primary care physicians, it will be more important than ever to screen patients for alcoholism and to become knowledgeable enough to discuss a variety of treatment referral options with affected patients. Fleming and colleagues12 recently confirmed earlier reports showing that brief physician advice can reduce alcohol consumption among certain drinkers. Responsible addiction treatment specialists are obligated to become informed regarding the appropriate use both of these new medications and of these behavioral treatments. Further, addiction treatment programs should be able to offer their patients more than 1 approach to alcohol treatment. Just as it is difficult in advance to specify which approaches will be effective with an individual hypertensive or depressed patient, it is also difficult to know in advance whether cognitive behavioral skill training alone or medications plus motivational enhancement therapy will be effective in arresting the course of alcohol dependence. The responsible and knowledgeable addiction treatment provider will monitor patients carefully and will turn to another medication and/or behavioral approach if there is lack of compliance with or lack of effect from the first approach.
Addiction medicine has recently become concerned with the issue of liver transplantation because alcoholics compose one of the largest groups receiving such transplants. There is a natural tendency to believe that alcoholics are not worthy of the precious commodity of a human organ, especially given the great financial cost, and that the results of such a transplant will ultimately be negative. In fact, follow-up studies of alcohol-dependent patients who have received liver transplants have shown positive results.14,15 The evidence suggests that the posttransplant rejection rate and longevity of alcoholics are at least as good as they are for those receiving liver transplants for other reasons. Clearly, this is an area that requires further study as criteria for selection of candidates for organ recipients are debated. It is also clear that physicians specializing in addiction medicine should be part of the evaluation team for liver transplantation. Alcoholic patients should receive follow-up in an alcoholism rehabilitation program after transplantation. Addiction medicine specialists should collaborate with transplant surgeons and hepatologists in the long-term care of posttransplant alcoholic patients. All such patients should be carefully monitored for early signs of relapse to alcoholic drinking, and all effective treatments should be available to them.
Addiction medicine has profited and continues to profit from scientific advances. While the current addiction treatments have greater efficacy than is generally known, they can certainly be made better. The recent scientific discoveries noted here are immediately pertinent to the treatment of addicted individuals, and it is time that scientifically evaluated methods are applied at the level of the individual patient.
1. Gianoulakis C. Krishnan B. Thavundayil J. Enhanced sensitivity of pituitary B-endorphin to ethanol in subjects at high risk of alcoholism. Arch Gen Psychiatry. 1996:53:250-257.
2. King AC, Volpicelli JR, Frazer A. O'Brien CP. Effect of naltrexone on subjective alcohol response in subjects at high and low risk for future alcohol dependence. Psychopharmacology. 1997;129:15-22.
3. Benjamin D, Grant EF. Pohorecky LA. Naltrexone reverses ethanol-induced dopamine release in the nucleus accumbens in awake, freely moving rats. Brain Res. 1993:621:137-140.o-parnine
4. VolpicelliJR. Ulm RR. The infiuence of control overappetitive and aversive events on alcohol preference in rats. Alcohol. 1990:7:133-136.
5. Volpicelli JR, Alterman AI, Hayashida M, Muentz L. O'Brien CP. Naltrexone and the treatment of alcohol dependence. In: Reid LD. ed. Opioids, Bulimia and Alcoholism. New York, NY: Springar-Verlag; 1990:195-214.
6. Volpicelli JR,Alterman AI. Hayashida M. O,Brian Cp. Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry. 1992:49:876-880.
7. O'Malley SS, Jaffe AJ, Chang G, Schottenfeld RS. Meyer RE, Rounsaville B. Naltrexone and coping skills therapy for alcohol dependence. Arch Gen Psychiatry. 1992: 49:881-887. '
8. Mason BJ. Ritvo EC, Morgan RO et al. A double-blind, placebo-controlled pilot study to evalute the efficacy and safety of oral nalmefene HC1 for alcohol dependence. Alcohol Clin Exp Res. 1994:18:1162-1167.
9. Sass H. Soyka M, Mann K. Zieglgasberger W. Relapse prevention by acamprosate: results from a placebo-controlled study on alcohol dependence. Arch Gen Psychiatry. 1996:53:673-680.
10. Littleton J. Acamprosate in alcohol dependence: how does it work? Addiction. 1995:90:1179-1188.
11. Project MATCH Research Group. Matching alcoholism treatments to client heterogeneity: Project MATCH posttreatment drinking outcomes. J Stud Alcohol. 1997: 58:7-29.
12. Fleming MF. Barry KL, Manwell LB, Johnson K. London R. Brief physician advice for problem alcohol drinkers: a randomized controlled trial in community-based primary care practices. JAMA. 1997:277:1039-1045.
13. Shelton W. Balint JA. Fair treatment of alcoholic patients in the context of liver transplanation. Alcohol Clin Exp Res. 1997:21:93-100.
14. Van Thiel DH, Gavaler J. Wright HI. Effect of alcohol use on allograft rejection rates after liver transplantation for alcoholic liver disease. Alcohol Clin Exp Res. 1995:19:1151-1155.
15. Gish RG, Lee AH, Keeffe EB, Rome H, Cancepcion W. Esquivel CO. Liver transplantation for patients with alcoholism and end-stage liver disease. Am J Gastroenterol. 1993:88:1337-1342.
From JAMA (Journal of the American Medical Association), June 18. 1997 Vol 277 No. 23 Contempo 1997.
