Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Acamprosate helped to increase abstinence in alcohol dependence

ACP J Club. 1996 Nov-Dec;125:71. doi:10.7326/ACPJC-1996-125-3-071


Source Citation

Whitworth AB, Fischer F, Lesch OM, et al. Comparison of acamprosate and placebo in long-term treatment of alcohol dependence. Lancet. 1996 May 25;347:1438-42.


Abstract

Objective

To determine whether acamprosate is an effective long-term (1-year) adjunct to psychosocial and behavioral treatment programs for adults with alcohol dependence.

Design

Randomized, double-blind, placebo-controlled trial.

Setting

5 hospitals in Austria.

Patients

455 adults (mean age 42 y, 79% men) met the inclusion criteria of hospitalization with chronic or episodic alcohol dependence, age 18 to 65 years, abstinence for ≥ 5 days, and elevated γ-glutamyl transpeptidase or mean corpuscular volume. Exclusion criteria were serious comorbid conditions, serious psychiatric disorders, or possibility of pregnancy.

Intervention

All patients received treatment for alcohol withdrawal that included psychosocial rehabilitation (n = 455). 224 patients received acamprosate (1998 mg/d if body weight was > 60 kg or 1332 mg/d if body weight was ≤ 60 kg), and 224 patients received placebo.

Main outcome measures

Self-reported and biochemically proven abstinence, time to first treatment failure (relapse or nonattendance), and side effects. A secondary outcome measure was the sum of all periods of total abstinence.

Main Results

Patients who received study medication or placebo were included in the intention-to-treat analysis (n = 448). At 1 year, 81.7% of patients who received acamprosate were not abstinent compared with 92.9% of pa-tients who received placebo (P = 0.007). {This absolute risk reduction in abstinence failure of 11.2% means that 9 patients would need to be treated with acamprosate for 1 year (compared with placebo) to have 1 additional patient remain abstinent, 95% CI 6 to 20; the relative risk reduction was 12%, CI 6% to 19%.}* The mean cumulative duration of abstinence was higher in the acamprosate group (139 vs 104 d, P = 0.012). The groups did not differ for 43 of 44 side effects, but patients in the acamprosate group had a higher rate of diarrhea (20% vs 12%, P = 0.021).

Conclusion

At 1 year, acamprosate was a safe and effective adjunct to psychosocial and behavioral treatment programs for adults with alcohol dependence.

Source of funding: Groupe LIPHA, France.

For article reprint: Prof. W.W. Fleischhacker, Department of Psychiatry, Innsbruck University Clinics, A-6020 Innsbruck, Austria. FAX 43-544-5368.

*Numbers calculated from data in article.


Commentary

Does acamprosate or any other drug really influence adults who abuse alcohol to drink less? Few clinical questions are as difficult to answer. Alcohol-dependent patients are notoriously uncooperative, and the criteria of success or failure have not been agreed on.

In the study by Whitworth and colleagues, 61% of participants dropped out during the 12 months of treatment so that the outcomes could only be evaluated in a minority of the patients. Unfortunately, this experience is common in studies of drug therapy for alcohol abuse (1, 2). Was treatment with acamprosate effective for those who stayed the course? A main outcome measure was time to first relapse. This method is weak because it ignores the severity of a relapse. Patients who drank themselves into a coma after 2 months of abstinence would have had a "better" outcome than patients who consumed a single glass of beer at 1 month.

How accurate was the method of detecting relapse? This study used 5 criteria: self-reported alcohol consumption, physical signs of alcoholism, tremor index, mean corpuscular volume, and γ-glutamyl transpeptidase. None of these tests, either alone or in combination, is highly sensitive or specific for alcohol consumption (3, 4).

So, can we agree that acamprosate is an effective adjunct to treatment for alcohol dependence? Not yet. The authors used an insensitive index of success: the time taken by each patient to "fall off the wagon"; to compound this problem, they used insensitive and nonspecific markers of the fall from the wagon.

This is a valiant pilot study of a new treatment that may be clinically important for general internists. But we must first see additional clinical trials in which adults who abuse alcohol are monitored with more sensitive and specific markers of response to drug therapy for the problem; such markers may include carbohydrate-deficient transferrins (4) or transdermal dosimetry (5).

Michael Phillips, MD
St. Vincent's Medical CenterStaten Island, New York, USA


References

1. de la Fuente JR, Morse RM, Niven RG, Ilstrup DM. Mayo Clin Proc. 1989;64:177-80.

2. Orrego H, Blake JE, Blendis LM, Compton KV, Israel Y. N Engl J Med. 1987;317:1421-7.

3. Watson RR, ed. Diagnosis of Alcohol Abuse. Boca Raton, Florida: CRC Press. 1989:69-100.

4. Litten RZ, Allen JP, eds. Measuring Alcohol Consumption. Psychosocial and Biochemical Methods. Totowa: Humana Press, 1992.

5. Phillips M, Greenberg J, Andrzejewski J. Alcohol Clin Exp Res. 1995;19:1547-9.