Alexander DeLuca, M.D.
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References and Resources:
Pharmacotherapy of Substance Use Disorders Collection
Compiled by Alexander DeLuca, M.D. 1999 - 2005.   Most recent additions: 2006-09-10 - New!.
This Collection is organized into the following Series: Acamprosate calcium (Campral)  //  Disulfiram (Antabuse) 
See also these related resources:  Archive of Naltrexone Full Text Articles and the
Naltrexone FAQ

Acamprosate (Campral)

!! Read This Before Emailing Me Regarding Acamprosate calcium (Campral) !! by Alexander DeLuca, 8/21/2004.

Harm Reduction and Individually Focused Alcohol Prevention
Neighbors et al.; IJDP; 17(4); 2006
"[A] brief overview of harm reduction and individually focused alcohol prevention strategies. Universal, selective, and indicated prevention strategies are described...
Zero-tolerance approaches continue to be the norm in... the US, despite research suggesting that harm reduction approaches can be effective. [E]xisting evidence supports that harm reduction shows considerable promise in universal prevention and have become best practices..."
See also:
The MM Programme in 2004: What Type of Drinker Seeks Controlled Drinking?
Ana Kosok, MM Program Director; IJDP; 2006
Overview of HR Treatments for Alcohol Problems - Witkiewitza, and  Marlatt; IJDP; 17(4); 285-294; 2006
Are Alcoholism Treatments Effective? The Project Match Data (PDF) - Cutler and Fishbain; 2005
Symposium on Moderation Management - Kern, Rotgers, and DeLuca; 109th APA; 2001

A Combined Behavioral Intervention for Treating Alcohol Dependence [for the COMBINE Study]
Miller, Moyers, and Arciniega; from: Miller (Ed): Combined Behavioral Intervention Therapist Manual (COMBINE); 2005.
Comment (DeLuca):
CBI is a modular, manual-guided, semi-structured therapy integrating evidence based behavioral methods developed as the state of the art psychotherapy to be tested in the COMBINE Study. Structured around Motivational Interviewing, CBI includes assessment, feedback, and highly individualized treatment plan development that is flexible regarding treatment goal.

This Poster Presentation is a sneak preview of the CBI Therapist Manual
(in press). CBI is probably the most thoughtfully designed, research based substance abuse therapy ever created. Clinicians, especially, will want to study this.

See also:
A Group Motivational Treatment for Chemical Dependency
Foote, DeLuca, Magura, Warner, Grand, Rosenblum and Stahl; J. Substance Abuse Treatment; 17(3); 1999
Naltrexone for the Treatment of Alcoholism - a Meta Analysis of Randomized, Controlled Trials - Srisurapanont, 2005
Long-Acting Injectable Naltrexone [Vivitrol] for Alcohol Dependence - A Randomized Controlled Trial
James  Garbutt et al; JAMA; 293; 2005-04-06

New! - Design and Analysis of Trials of Combination Therapies [in the COMBINE Study]
Hoskings et. al; J Stud. Alcohol; 2005
Choosing Pharmacotherapies for the COMBINE Study - Process and Procedures
Swift and Pettinati; J Stud. Alcohol; 2005

When Worlds Collide: [The COMBINE Study] Blending Pharmacotherapy and Psychotherapy Research
W.R. Miller, et al.; J Stud. Alcohol; 2005
Comment (DeLuca):
The COMBINE trial is designed to study the efficacy (alone and combined) of naltrexone and acamprosate with 'medical management' and a psychotherapy treatment known as the Combined Behavioral Intervention. The Study is in progress. I will post more interim articles soon.
Related resources: 
Disulfiram collection  ;  Acamprosate collection  ;  Naltrexone collection
Abstinence and Harm Reduction for Alcohol - Academic Literature archives
See also:
Comparing and Combining Naltrexone and Acamprosate - A Double-blind, Placebo-Controlled Study
Falk Kiefer, et. al.; Archives of General Psychiatry; 60(1); 2003
Efficacy and Safety of Naltrexone and Acamprosate in the Treatment Of Alcohol Dependence: A Systematic Review
Bouza  Carmen, et al.; Addiction; 99(7):811-828; 2004
A 1-Year Pragmatic Trial of Naltrexone vs. Disulfiram in the Tx of Alcohol Dependence - deSouza and deSouza; Alcohol and Alcoholism; 2004.
Harm Reduction: Meeting Clients Where They Are - Kate Jackson, Social Work Today, 4(6), 2004.

Updated! (2005-12-30)
Does Naltrexone Cause Permanent Liver Disease? (No) - Can Naltrexone be Used in the Presence of Liver Disease (Carefully)
[References with Abstract from Medline Search for 'naltrexone' and 'hepatotoxicity'] -
Alex DeLuca, M.D.; 2001-06-16; Updated: 2005-12-30
"A review of the literature indicates that even when given at much higher doses than are needed for treating heroin or alcohol abusers, there is no evidence that naltrexone causes clinically significant liver disease or exacerbates, even at high doses, serious pre-existing liver disease." [Brewer et al.; Addiction .Biology; 2004]

Can Campral Cure Alcohol Abuse? - Suzanne Anderson; Journal of Addictive Disorders; 2004 -- "A serious concern is the challenge of getting the new treatments to the addicts. Our health and social policies coupled with financial priorities seem to work to keep addicts from receiving treatment. Blaming the alcoholic is still a prevalent attitude."

Comment (DeLuca):
More accessible to the non-scientist reader than most of the articles on this site about acamprosate, this article reviews the history of the development of Campral and covers most of the major studies along the way, and discusses some problems with treatment.
A pretty good review.


Campral Appears Safe, Well-Tolerated in Long-Term Treatment  by DGNews; Doctor’s Guide; 4/15/2005

Yes, but is there any there, there?

Predictors of Acamprosate Efficacy: Results from a Pooled Analysis of Seven European Trials by R. Verheul et al; Psychopharmacology (Berlin); 2005. -- "Acamprosate efficacy was not differentially associated with any of the predictor variables. Importantly, the hypotheses were rejected despite the large sample size and sufficient statistical power."

Another underwhelming acamprosate study. Hypotheses Re: who might benefit most based on presumed pharmacological mechanism failed. All one can say is acamprosate may help some, but there is currently no way to predict whom.

United Kingdom Multicentre Acamprosate Study (UKMAS): A 6-Month Prospective Study Of Acamprosate Versus Placebo In Preventing Relapse After Withdrawal From Alcohol by J. Chick et. al.; Alcohol and Alcoholism 35(2); 176-187; 2000.

"In comparison with other published trials of acamprosate, patients started study medication after a longer time following detoxification, had more often recommenced drinking before medication was started and had a higher drop-out rate, and this might have contributed to the lack of a treatment effect in this study.    [emphasis mine  ..alex...]

Naltrexone Versus Acamprosate - One Year Follow Up of Alcohol Dependence Treatment (PDF) by Rubio et. al.; Alcohol & Alcoholism; 36(5); 2001.

"At the end of one year, 41% receiving naltrexone and 17% receiving acamprosate had not relapsed. The cumulative number of days of abstinence was significantly greater, and the number of drinks consumed at one time and the severity of craving were significantly less in the naltrexone group... as was the percentage of drinking days."

Comparing and Combining Naltrexone and Acamprosate in Relapse Prevention of Alcoholism by Kiefer et. al.; Arch Gen Psychiatry; 60(1); 2003.

"The combined medication was most effective with significantly lower relapse rates than placebo and acamprosate but not naltrexone... Naltrexone and acamprosate, especially in combination, considerably enhance the potential of relapse prevention."

Effect of the combination of naltrexone and acamprosate on alcohol intake in mice by Kim et. al; Psychiatry Clin. Neurosci.;  58(1); 2004.

"The results demonstrate that naltrexone, at the higher dose... significantly reduced alcohol consumption. When combined with naltrexone, acamprosate reduced alcohol consumption across both doses of naltrexone."

A Comparison of Two Intensities of Psychosocial Intervention for Alcohol Dependent Patients Treated with Acamprosate by Hammarberg et. al.; Alcohol & Alcoholism; 39(3); 2004.

"CONCLUSIONS: Adding more intensive individual treatments appears to add no extra improvement beyond that obtained by prescribing acamprosate and offering an infrequent consultation with a physician"

Efficacy & Safety of Naltrexone and Acamprosate in the Treatment of Alcohol Dependence - A Systematic Review by Carmen et. al.; Addiction; 99(7); 811 - 828; 2004.

"Acamprosate appears to be especially useful in a therapeutic approach targeted at achieving abstinence, whereas naltrexone seems more indicated in programmes geared to controlled consumption.  Both drugs are safe and acceptably tolerated..."

Alcohol Effects During Acamprosate Treatment by Brasser et. al.; Alcoholism: Clin. Exp. Res.; 28(7); 2004.

"RESULTS: Acamprosate alone did not substantially affect subjective, physiological, or psychomotor performance measures. Acamprosate did not alter alcohol pharmacokinetics, or alcohol-induced behavioral impairment or tachycardia, and most subjective alcohol effects were also unaltered by acamprosate as well."

Press Release Announcing FDA Approval of acamprosate calcium (Campral) in PDF format -- from Forest Laboratories, 7/29/2004.

"The mechanism of action of Campral in maintenance of alcohol abstinence is not completely understood. Chronic alcohol exposure is hypothesized to alter the normal balance between neuronal excitation and inhibition. Campral interacts with neurotransmitter systems and is hypothesized to restore the normal balance. This mechanism of action is different from that ascribed to currently available medications, which either block the 'high' associated with alcohol or induce vomiting if alcohol is ingested."
Comment: Ahh, OK; 'restores normal balance,' but not well understood. Is anybody else feeling decidedly underwhelmed?

Acamprosate calcium (Campral) Prescribing Information  in PDF format--  from Forest Laboratories, 2004.

"In a fourth study, the efficacy of CAMPRAL was evaluated in alcoholics, including patients with... polysubstance abuse and patients who had not undergone detoxification and who were not required to be abstinent at baseline. This study failed to demonstrate superiority of CAMPRAL over placebo."

Acamprosate Enhances N-Methyl-D-Apartate Receptor-Mediated Neurotransmission But Inhibits Presynaptic GABA Receptors in Nucleus Accumbens Neurons [Abstract]  --  by Fulvia Berton, et. al.; Alcoholism: Clinical & Experimental Research; 22 (1); 1998.

"Acamprosate (calcium acetylhomotaurine) is used therapeutically in Europe to reduce relapse in weaned alcoholics. However, the mechanisms of acamprosate action in the central nervous system are still obscure, although early studies suggested an action on GABA receptors."

Acamprosate (Campral) Summary by Mary Elchisak, 2001.

Comment: Month after month this document is one of the most viewed on this website; which completely baffles me <g>. Now reformatted for easier reading and HTML Print version added.   ..alex...

[END: Series - Acamprosate (Campral)]
Disulfiram (Antabuse)
My Experience with Antabuse - by James Cannon; Moderation Management; 2004 -- "Taking Antabuse is a proactive way of achieving abstinence for whatever timeframe... seems appropriate... It removed the alcohol factor from my emotional life. The results were useful and unexpected. "

See also:
Characteristics and Motives of Problem Drinkers Seeking Help from Moderation Management Klaw; '03
"... presents survey data on the characteristics and help-seeking motives of 467 individuals..."

A One-Year Pragmatic Trial of Naltrexone vs. Disulfiram in the Treatment of Alcohol Dependence by deSouza & deSouza; Alcohol & Alcoholism; 39(6); pages 528-531; 2004 -- "[T]he number of patients that remained abstinent with Disulfiram were twice that with Naltrexone. The survival time till the first relapse was greater with Disulfiram [and the] number who were abstaining at the end of one year was [much greater]. Naltrexone patients had significantly lower [craving] scores..."

Does Disulfiram Have a Role in Alcoholism Treatment Today?  by Fuller & Gordis; Addiction 99(1); 21-24; 2004.  

Excellent, recent review of the issues surrounding disulfiram (Antabuse) therapy making the point that supervised administration is both safe and effective.

See also:
Commentaries about the above article from other expert clinicians and researchers regarding safety and psychological aspects of disulfiram therapy:
Commentaries (PDF); Addiction; 99(1); 2004.

12-month, Randomized Controlled Trial of Family-Supervised Disulfiram vs. Family-Supervised Naltrexone* (Abstract) by deSouza & deSouza; Alcohol & Alcoholism (in press)

"[T]he number of patients that remained abstinent with Disulfiram were twice that with Naltrexone. The survival time till the first relapse was greater with Disulfiram... The number who were abstaining at the end of one year was 86% with Disulfiram compared to 56% with Naltrexone. However, the Naltrexone patients had significantly lower [craving] scores..."

Disulfiram for alcohol abuse: Why is such an effective drug so under-prescribed? by Colin Brewer,  Primary Care in the New NHS ; 2001

"[Looking at] only those studies in which disulfiram was [supervised] as part of the treatment programme, we find that out of 13 controlled and 5 uncontrolled studies, all but one are positive, and often very strongly positive."

Medications that can help us avoid relapse in early recovery. Alex DeLuca; 1996.

A patient hand-out regarding the use of Antabuse (disulfiram) and naltrexone (ReVia) as pharmacologic aids in early recovery from alcohol, cocaine, or opiate dependence. I just can't say this stuff any better.

Medications that might help problem drinkers achieve moderation goals by Alex DeLuca; 2001.

A patient hand-out regarding the use of naltrexone (ReVia) as an aid to early recovery for people with a goal of moderation rather than abstinence.

Antabuse Plus Buprenorphine May Help Treat Those Addicted To Cocaine; Doctor's Guide to the Internet; June 14, 2000.

"[M]ore than 50 percent of individuals addicted to opiates such as heroin also are addicted to cocaine. A study in the Spring 2000 issue of Biological Psychiatry reports that combining buprenorphine... with disulfiram (Antabuse) was more effective than buprenorphine alone in reducing cocaine use in persons with this dual addiction."

[END: Series - Disulfiram (Antabuse)]

Addiction, Pain, and Public Health website

Alexander DeLuca, M.D.

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Originally posted:  2004-06-15

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