Evidence-Based Reviews

Treating alcohol dependence: When and how to use 4 medications

Current Psychiatry. 2008 February;7(2):25-37

References

1. National Institutes of Health. Helping patients who drink too much: a clinician’s guide. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism; 2007. NIH Publication 07-3769. Available at: http://www.niaaa.nih.gov/Publications/EducationTrainingMaterials/guide.htm. Accessed January 3, 2008.

2. Substance Abuse and Mental Health Services Administration. National Survey of Substance Abuse Treatment Services: 2005. Data on substance abuse treatment facilities, (DASIS Series: S-34). Rockville, MD: Office of Applied Studies, 2006. DHHS Publication (SMA) 06-4206.

3. Substance Abuse and Mental Health Services Administration. Treatment episode data set (TEDS) highlights 2005: National admissions to substance abuse treatment services. Rockville, MD: Office of Applied Studies. 2006. DHHS Publication (SMA) 07-4229.

4. Hasin DS, Stinson FS, Ogburn EO, Grant BF. Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States. Arch Gen Psychiatry 2007;64(7):830-42.

5. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) study. JAMA. 1990;264(19):2511-8.

6. Mariani JJ, Levin FR. Treatment of comorbid conditions of substance abuse. Directions in Psychiatry 2005;25(2):129-39.

7. Fuller RK, Branchey L, Brightwell DR, et al. Disulfiram treatment of alcoholism. A Veteran’s Administration cooperative study. JAMA. 1986;256:1449-55.

8. Fuller RK, Roth HP. Disulfiram for the treatment of alcoholism. An evaluation of 128 men. Ann Intern Med. 1979;90:901-4.

9. Schuckit MA. A one-year follow-up of men alcoholics given disulfiram. J Stud Alcohol 1985;46:191-5.

10. Collins GB, McAllister MS, Adury K. Drug adjuncts for treating alcohol dependence. Cleve Clin J Med 2006;73(7):641-4.

11. Goyer PF, Major LF. Hepatotoxicty in disulfiram treated patients. J Stud Alcohol 1979;40:133-7.

12. Ranek L, Buch Andreasen P. Disulfiram hepatotoxicity. Br Med J 1977;2(6079):94-6.

13. Björnsson E, Nordlinder H, Olsson R. Clinical characteristics and prognostic markers in disulfiram-induced liver injury. J Hepatol 2006;44(4):791-7.

14. Enghusen PH, Loft S, Anderson JR, et al. Disulfiram therapy—adverse drug reactions and interactions. Acta Psychiatr Scand 1992;86(369):59-66.

15. Volpicelli JR, Volpicelli LA, O’Brien CP. Medical management of alcohol dependence: clinical use and limitations of naltrexone treatment. Alcohol Alcohol 1995;30:789.-

16. de Wit H, Svenson J, York A. Non-specific effect of naltrexone on ethanol consumption in social drinkers. Psychopharmacology (Berl) 1999;146:33.-

17. Monterosso JR, Flannery BA, Pettinati HM, et al. Predicting treatment response to naltrexone: the influence of craving and family history. Am J Addict 2001;10:258-68.

18. Srisurapanont M, Jarusuraisin N. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev 2005;(1):CD001867.-

19. Anton RF, O’Malley SS, Ciraulo DA, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006;295:2003-17.

20. Monti PM, Rohsenow DJ, Swift RM, et al. Naltrexone and cue exposure with coping and communication skills training for alcoholics: treatment process and 1-year outcomes. Alcol Clin Exp Res 2001;25:1634-47.

21. Garbutt JC, Kranzler HR, O’Malley SS, et al. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA. 2005;293(13):1617-25.

22. Doering PL. Substance-related disorders: alcohol, nicotine, and caffeine. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: a pathophysiologic approach. 4th ed. Stamford, CT: Appleton & Lange; 1999.

23. Mann K, Lehert P, Morgan MY. The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis. Alcohol Clin Exp Res 2004;28(1):51-63.

24. Paille FM, Guelfi JD, Perkins AC, et al. Double-blind randomized multicentre trial of acamprosate in maintaining abstinence from alcohol. Alcohol Alcohol 1995;30:239-47.

25. Chick J, Howlett H, Morgan MY, Ritson B. United Kingdom Multicentre Acamprosate Study (UKMAS): a 6-month prospective study of acamprosate versus placebo in preventing relapse after withdrawal from alcohol. Alcohol Alcohol 2000;35(2):176-87.

26. Mason BJ, Goodman AM, Chabac S, Lehert P. Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: the role of patient motivation. J Psychiatr Res 2006;40(5):383-93.

27. Mason BJ. Treatment of alcohol-dependent outpatients with acamprosate: a clinical review. J Clin Psychiatry 2001;62(suppl 20):42-8.

28. Johnson BA, Ait-Daoud N, Bowden CL, et al. Oral topiramate for treatment of alcohol dependence: a randomized controlled trial. Lancet 2003;361(9370):1677-85.

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CASE CONTINUED: Planning treatment

A combination of behavioral therapy and pharmacotherapy is appropriate for treating Mr. G’s alcohol dependence. When you discuss the diagnosis with him, he endorses a goal of abstinence. For behavioral therapy, he says he would like to try Alcoholics Anonymous, which helped a friend “turn his life around.”

He has become accustomed to taking escitalopram once daily but is hesitant to take any medication that requires more frequent dosing. He also worries that medication might impair his work performance, which requires extensive periods of concentration. Your goal—as you consider available medications—is to develop a treatment plan that incorporates Mr. G’s preferences and addresses his concerns.

Disulfiram

Disulfiram, an irreversible aldehyde dehydrogenase inhibitor, is indicated for maintaining enforced sobriety in patients with chronic alcohol dependence (Table 1). Aldehyde dehydrogenase inhibition disrupts alcohol-to-acetate metabolism, which leads to acetaldehyde accumulation. If a disulfiram-treated patient ingests alcohol, increased acetaldehyde levels lead to the unpleasant “disulfiram-ethanol reaction,” with diaphoresis, flushing, nausea, vomiting, headache, tachycardia, and hypotension. The reaction’s severity is proportional to the disulfiram dose and amount of alcohol consumed.

Patients taking disulfiram must abstain from all alcohol, including over-the-counter cold remedies and mouthwashes containing alcohol. Advise patients that ingesting small amounts of alcohol can induce symptoms, even days after taking disulfiram.

Efficacy. Clinical trial results with disulfiram have been mixed. In the largest controlled study to date, Fuller et al⁷ found no significant difference in rates of total abstinence, time to first drink, employment, or social stability measures at 1 year among 605 men who received counseling plus disulfiram, 250 mg/d, or placebo. Other disulfiram studies have found a modest decrease in the frequency of drinking but no effect on abstinence rates.^8,9

Because medication adherence is the strongest predictor of outcome with disulfiram,¹⁰ monitoring for adherence and stressing its importance to patients may increase the drug’s efficacy. Disulfiram may be most effective in highly motivated patients with stable social support or as an adjuvant to an outpatient treatment program.

Clinical Point

Drowsiness, a common complaint with disulfiram, is often self-limited and can be reduced by evening dosing

Administration. Disulfiram is available in 250-mg tablets and is usually dosed from 125 to 500 mg/d. Treatment can begin after patients abstain from alcohol for ≥12 hours and have a serum alcohol concentration of zero.

Side effects. Drowsiness is a common complaint with disulfiram; this adverse effect is frequently self-limited and can be reduced by evening dosing.

Subclinical liver enzyme elevations have been reported in 25% of patients taking disulfiram.¹¹ Although rare, potentially fatal hepatotoxicity has been reported^12,13 (with a dose as low as 200 mg/d¹²), typically occurring early in treatment and associated with jaundice and fever. One study estimated the risk of dying of hepatotoxicity caused by disulfiram to be 1 in 30,000 patients/year.¹⁴

A recent Swedish study¹³ reviewed data from 1966 through 2002 and found 82 cases of drug-induced liver injury associated with disulfiram. By comparing these findings with sales figures from 1972 to 2002, the authors report an incidence of disulfiram-induced liver injury of about 1 case per 1.3 million estimated average daily doses.

Order liver function tests at baseline, then retest 10 to 14 days after starting disulfiram and again approximately 4 weeks later. Thereafter, monitoring once every 3 to 6 months is generally sufficient in patients without liver disease symptoms.

Clinical Point

Naltrexone’s effect might have a genetic component, as suggested by greater benefit in persons with a family history of alcoholism

Other serious adverse events associated with disulfiram therapy include optic neuritis, peripheral neuritis, cholestatic hepatitis, seizures, and arrhythmias. Psychosis also can occur, generally with dosages ≥500 mg/d. Avoid concomitant use of disulfiram and metronidazole, which can cause acute psychosis.

Disulfiram-related inhibition of cytochrome P-450 can increase serum levels and toxicity risk of medications metabolized in the liver, such as warfarin, phenytoin, and isoniazid. Patients taking concomitant warfarin and disulfiram require close monitoring for increases in the international normalized ratio (INR).

Contraindications. Disulfiram is contraindicated in patients with ischemic heart disease and those who are pregnant. Also avoid disulfiram in patients with cerebrovascular disease, diabetes mellitus, psychosis, or cognitive impairment.

Recommendation. Disulfiram is a valid option for treating alcohol dependence in a select group of highly motivated patients who are medically and psychiatrically stable and in whom adherence can be closely monitored.

Table 1

Disulfiram: Fast facts

Mechanism: Acetaldehyde accumulates when aldehyde dehydrogenase is inhibited
FDA-approved for alcohol dependence: Yes
Dosing: 125 to 500 mg once daily
Effect: Aversive reaction to alcohol
Potential side effects: Liver toxicity, seizures, arrhythmia, peripheral neuropathy, psychosis
Contraindications: Concurrent alcohol consumption, severe cardiac disease, psychosis, pregnancy
Comments: Many drug interactions, including warfarin, metronidazole, and phenytoin; monitor liver function for toxicity