Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

28. Matching and Differential Therapies 645adjunct for the treatment of alcohol dependence remains disulfiram (Antabuse).Disulfiram interferes with normal metabolism of alcohol, which results inan accumulation of acetaldhyde; hence, drinking following ingestion of disulfiramresults in an intense physiological reaction, characterized by flushing,rapid or irregular heartbeat, dizziness, nausea, and headache (see Nace, Chapter5, this volume). Thus, disulfiram treatment is intended to work as a deterrent todrinking. Despite the sustained popularity and widespread use of disulfiram, alandmark multicenter, randomized clinical trial found that disulfiram was nomore effective than inactive doses of disulfiram or no medication in terms ofrates of abstinence, time to first drink, unemployment, or social stability (Fulleret al., 1986). However, for subjects who did drink, disulfiram treatment wasassociated with significantly fewer total drinking days. Rates of compliancewith disulfiram in the study were low (20% of all subjects), but abstinence rateswere reasonably good (43%) among compliant subjects. This study highlightsseveral important problems with the use of disulfiram: (1) Compliance is amajor problem and must be monitored closely, and (2) many patients areunwilling to take disulfiram (62% of those eligible for the study refused to participate).Thus, several investigators have evaluated the effectiveness of behavioraltreatments to improve retention and compliance with disulfiram. One of themost effective strategies is disulfiram contracts, in which the patient’s spouse ora significant other agrees to observe the patient take disulfiram each day andreward the patient for compliance with disulfiram treatment (O’Farrell, Cutter,Choquette, & Floyd, 1992). Azrin, Sisson, Meyers, and Godley (1982) reportedpositive and durable results from a randomized clinical trial comparingunmonitored disulfiram to disulfiram contracts, where disulfiram ingestion wasmonitored by the patient’s spouse or administered as part of a multifacetedbehavioral program, the CRA. A broad-spectrum approach developed by Huntand Azrin (1973), CRA incorporates skills training, behavioral family therapy,and job-finding training, as well as a disulfiram component. CRA has beenfound to be significantly more effective than traditional group approaches infostering abstinence. Combined disulfiram–behavioral treatment for alcoholdependence illustrates how a pharmacotherapy that may be marginally effectivewhen used alone can be highly effective when used with in combination withtreatments that foster compliance and target other aspects of substance abuse.Another major development in the treatment of alcohol dependence wasthe recent Food and Drug Administration (FDA) approval of naltrexone. Theapplication of naltrexone, an opioid antagonist, to the treatment of alcoholismderives from findings that naltrexone reduces alcohol craving and use inhumans. In randomized clinical trials, naltrexone has been shown to be moreeffective than placebo in reducing alcohol use and craving (O’Malley et al.,1992; Volpicelli, Alterman, Hayashida, & O’Brien, 1992). As with disulfiram,best responses are seen among patients who are compliant with naltrexone