Is Naltrexone a Cure for Alcoholism Effectiveness Compared to Acamprosate and Placebo

Naltrexone is an opioid receptor antagonist (it blocks opioid receptors in the brain), which is used in the treatment of drug addiction and alcoholism. The way in which naltrexone works is not fully understood. It is thought that, by blocking opioid receptors, naltrexone reduces the release of dopamine. This decreases the feel-good effects of alcohol consumption. 

Mainstream studies

Naltrexone has been shown to have a modest effect in preventing relapse in alcoholics in controlled clinical trials. 

Naltrexone compared to placebo

Streeton and Whelan (ref. 1) conducted a meta-analysis of 7 studies published in 1976-2001. All the studies lasted for 12 weeks and involved 804 subjects in total. In all cases, naltrexone was combined with psychotherapy or another form of rehabilitation.

When the authors looked at the individual results of each study, two of the seven studies showed naltrexone was more effective than placebo in decreasing the rate of return to heavy drinking. Only one study showed a higher abstinence rate with naltrexone than with placebo.

When the results of all seven studies were pooled, naltrexone was found to be more effective overall than placebo. The number of subjects relapsing to heavy drinking was 14% lower with naltrexone. Abstinence was 10% higher with naltrexone. Subjects given naltrexone consumed alcohol on 3% fewer days and had one standard drink less per day when they did drink than subjects given placebo.

The authors note that one study with an additional follow-up period showed that the benefit of 12 weeks naltrexone treatment was lost 6 months after the therapy was stopped.

Another meta-analysis by Srisurapanont and Jarusuraisin (ref. 2) looked at 24 studies on a total of 2861 subjects. The studies varied in length from 4 weeks to 2 years. The authors also obtained results of unpublished studies from the manufacturer of naltrexone.

The analysis showed that short-term treatment with naltrexone decreased the relapse rate by 36%. However, after 12 weeks, naltrexone was superior to placebo only in the time to the first drink and intensity of craving.

Approximately 36% of subjects stopped treatment in the first 12 weeks. This could have been related to side-effects of dizziness, nausea and fatigue.

The rate of relapse was found to be reduced in one 12-month study, but the authors were critical of the study design. The authors also criticized the short duration of most studies and the small numbers of subjects involved. They concluded that naltrexone may be useful in an overall program, but should always be combined with some form of psychosocial treatment, such as cognitive behavioral therapy.

Naltrexone compared to Acamprosate (Campral)

Rösner and colleagues (ref. 3) conducted a meta-analysis of studies in which the effect of naltrexone was compared to that of acamprosate. The authors distinguished between the concept of having a first drink (lapse) and returning to heavy drinking (relapse).

Naltrexone was found to have some effect both in supporting subjects in their efforts to remain abstinent and in preventing heavy drinking. Acamprosate was useful in supporting abstinence. However, once a lapse occurred, acamprosate did not influence the amount of alcohol consumed subsequently.

Comparing the efficacy of both drugs, the authors concluded that acamprosate is better at preventing a lapse, while naltrexone is better in preventing a lapse from turning into a full relapse.

Kiefer and colleagues (ref. 4) conducted the first study that not only compared naltrexone and acamprosate used alone, but also combined therapy with both drugs. 160 subjects were given naltrexone, acamprosate, naltrexone plus acamprosate, or placebo for 12 weeks.

Each of the active treatments were found to be more effective than placebo. Subjects given naltrexone alone had better results with respect to time to first drink and time to relapse than subjects given acamprosate alone. However, the best results were obtained with the combined treatment.

The Sinclair Method: naltrexone as a means to achieve controlled drinking

David Sinclair developed his method (refs. 5 , 6) following observations on laboratory rats. He moved to Finland in 1972, where the method has since been accepted into mainstream practice.

The Sinclair method uses low-dose naltrexone, which is only taken on days when the subject drinks. Sinclair’s premise is that by reducing craving, naltrexone can help an alcoholic to turn into someone who is in sufficient control to continue drinking within safe limits, even if he or she does not choose to move to full abstinence.

Sinclair claims a 78% success rate over 3-4 months, with one study showing 50% success after 3 years. Success is defined either as abstinence or as controlled drinking within safe limits. Sinclair also claims that 76 studies have shown his method to be safe and effective.

Two subjects using the method have described their experiences as follows:

“Oh yes, I still enjoy good wine. I savour wine. But there's no craving.”

“With naltrexone, it's weird. You drink and you feel the effect of the alcohol but it doesn't have the magic.”

The Sinclair method continues to be viewed with suspicion by the majority of alcoholism practitioners outside Finland. It is highly controversial, because it does not seek to impose total abstinence, which is the usual goal of alcoholism treatment and of programs such as the “12 Steps” of Alcoholics Anonymous. In fact, having the subject continue drinking as long and as much as he or she wishes is a fundamental concept of the method. Since mainstream studies of naltrexone use abstinence as the main criterion, it is also not possible to compare their results with studies of the Sinclair method.

The Sinclair method is reporting success rates that are significantly higher than those achieved by other pharmacological and psychosocial treatments. However, its full validation and acceptance demands a radical shift in attitudes from mainstream practitioners.


1. C. Streeton and G. Whelan

Naltrexone, a relapse prevention maintenance treatment of alcohol dependence: a meta-analysis of randomized controlled trials

Alcohol and Alcoholism Vol. 36, No. 6, pp. 544-552, 2001  Full text 

2. M. Srisurapanont and N. Jarusuraisin

Naltrexone for the treatment of alcoholism: a meta-analysis of randomized controlled trials

International Journal of Neuropsychopharmacology Vol. 8, pp. 1–14, 2005 Full text pdf 

3. S. Rösner et al

Acamprosate supports abstinence, Naltrexone prevents excessive drinking: evidence from a meta-analysis with unreported outcomes

Journal of Psychopharmacology, Vol. 22, No. 1, pp. 11-23, 2008

4. F. Kiefer et al

Comparing and Combining Naltrexone and Acamprosate in Relapse Prevention of Alcoholism : A Double-blind, Placebo-Controlled Study

Archives of General Psychiatry, Vol. 60, pp. 92-99, 2003

5. P. Wark

Naltrexone: can a pill cure alcoholism?

The Times, January 12 2009

6. J.D. Sinclair

Evidence about the use of naltrexone and for different ways of using it in the treatment of alcoholism

Alcohol and Alcoholism, Vol. 36, No. 1, pp. 2-10, 2001  Full text 

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taiyu john robertson
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Posted on Jun 8, 2010