Disulfiram treatment of alcoholism. A Veterans Administration cooperative study

Fuller, Richard K.

doi:10.1001/jama.256.11.1449

Cited by 290 publications

(194 citation statements)

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“…Disulfiram (Antabuse s ) has been used for over 50 years in the treatment of alcoholism (Fuller et al, 1986). Disulfiram inhibits the enzyme aldehyde dehydrogenase, which results in the accumulation of acetaldehyde, a toxic metabolic intermediate, upon ethanol ingestion.…”

Section: Disulfiram and Cocaine Dependencementioning

confidence: 99%

There and Back Again: A Tale of Norepinephrine and Drug Addiction

Weinshenker

Schroeder

2006

Neuropsychopharmacol

319

277

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Fueled by anatomical, electrophysiological, and pharmacological analyses of endogenous brain reward systems, norepinephrine (NE) was identified as a key mediator of both natural and drug-induced reward in the late 1960s and early 1970s. However, reward experiments from the mid-1970s that could distinguish between the noradrenergic and dopaminergic systems resulted in the prevailing view that dopamine (DA) was the primary 'reward transmitter' (a belief holding some sway still today), thereby pushing NE into the background. Most damaging to the NE hypothesis of reward were studies demonstrating that NE receptor antagonists and NE reuptake inhibitors failed to impact drug self-administration. In recent years new tools, such as genetically engineered mice, and new experimental paradigms, such as reinstatement of drug seeking following withdrawal, have propelled NE back into the awareness of addiction researchers. Of particular interest is disulfiram, an inhibitor of the NE biosynthetic enzyme dopamine b-hydroxylase, which has demonstrated promising efficacy in the treatment of cocaine dependence in preliminary clinical trials. The purpose of this review is to synthesize the new data linking NE to critical aspects of DA signaling and drug addiction, with a focus on psychostimulants (eg, cocaine), opiates (eg, morphine), and alcohol.

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Section: Disulfiram and Cocaine Dependencementioning

confidence: 99%

There and Back Again: A Tale of Norepinephrine and Drug Addiction

Weinshenker

Schroeder

2006

Neuropsychopharmacol

319

277

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“…Naltrexone can be used for treating both opioid (Greenstein et al, 1997) and alcohol (O'Malley et al, 1992;Volpicelli et al, 1992) dependence. Disulfiram has shown some efficacy in reducing alcohol use (Fuller et al, 1986;Chick et al, 1992), as well as cocaine use (Carroll et al, 1993Petrakis et al, 2000;George et al, 2000). Although the mechanisms of action may differ across the drug classes, the beneficial effects could only be discerned by including polysubstance abusers in the trials and evaluating the effects of these medications on use of multiple substances.…”

Section: Limited Generalization Of Safety and Efficacy Findingsmentioning

confidence: 99%

Single versus multiple drug focus in substance abuse clinical trials research

Rounsaville

Petry

Carroll

2003

Drug and Alcohol Dependence

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Complex patterns of multiple substance use pose clinical and methodological challenges for substance abuse clinical trials research. To increase measurement precision and internal validity, the modal approach has been to target both treatment interventions and outcome assessment to a single class of abused substance. This strategy warrants reconsideration because it entails limitations in recruitment feasibility and generalization of study findings. This report reviews pros and cons of single versus multiple targeted drugs, suggests guidelines for choosing between these strategies and outlines methods for broadening the scope of substance abuse clinical trails to take abuse of multiple substances into account. We recommend that investigators consider moving away from a single drug focus in three ways. First, include systematic assessment of a wide range of psychoactive substance use throughout the trial and evaluate the impact of study treatments on use of all classes of drugs. Second, except where contraindicated, include patients who use and abuse multiple classes of substances even in trials evaluating treatment of a single targeted drug. Third, consider inclusion of polysubstance abusers or those who primarily abuse multiple classes of substances in the same clinical trial. Although many treatment efficacy questions can best be answered by single focus studies, we recommend that such designs be adopted only after less restrictive designs are first considered.

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“…Disulfiram has been used in the treatment of substance use disorders since its approval in 1948, first in alcohol-dependent populations, where it has shown varied levels of efficacy in randomized trials (Chick et al, 1992;Fuller et al, 1986;Ling, Weiss, Charuvastra, & O'Brien, 1983). More recently, studies evaluating the efficacy of disulfiram treatment in cocaine-dependent populations have suggested promising results (Carroll, Nich, Ball, McCance-Katz, & Rounsaville, 1998;George et al, 2000;Petrakis et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, sex effects remain a critical but understudied area in substance abuse treatment (Schuckit, 1985). For example, of the 1289 individuals treated in the five landmark studies evaluating the effectiveness of disulfiram treatment of alcohol use disorders (Chick et al, 1992;Fuller et al, 1986;Ling et al, 1983;Fuller & Roth, 1979), only 20 (1.5%) were women. No women were included in the three studies that were double blind and placebo controlled.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in cocaine-dependent individuals' response to disulfiram treatment

Nich

McCance‐Katz

Petrakis

et al. 2004

Addictive Behaviors

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The objective of this study is to evaluate differential response to disulfiram treatment of cocaine dependence by sex. Sex by treatment interactions from two pooled randomized clinical trials involving 191 cocaine-dependent subjects (36% female) were evaluated. Primary outcomes were days of abstinence and percentage of drug-free urine specimens. Significant sex by treatment interactions were found, where men treated with disulfiram had better outcomes than those who were not. Women had an intermediate outcome regardless of whether they received disulfiram. Sex differences in response to disulfiram treatment have important clinical and theoretical implications. Reasons for this apparent sex-based response are not clear, but possible mechanisms worthy of greater study include differences in alcohol use by sex as well as differences in dopamine-mediated responses to cocaine and disulfiram.

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Disulfiram treatment of alcoholism. A Veterans Administration cooperative study

Cited by 290 publications

References 0 publications

There and Back Again: A Tale of Norepinephrine and Drug Addiction

There and Back Again: A Tale of Norepinephrine and Drug Addiction

Single versus multiple drug focus in substance abuse clinical trials research

Sex differences in cocaine-dependent individuals' response to disulfiram treatment

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