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.

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Clinical Point

Limited data comparing topiramate with placebo found a reduction in drinking and increased abstinence

Administration. Start with 25 mg/d and increase over several weeks to 300 mg/d, given in divided doses.

Side effects include dizziness, paresthesia, somnolence, difficulty concentrating, and weight loss. Because topiramate is excreted renally, reduce doses by 50% in patients with CrCl

Other renal side effects include an elevated risk of nephrolithiasis. Topiramate’s inhibition of carbonic anhydrase can reduce bicarbonate levels, leading to a nonanion gap metabolic acidosis.

Table 4

Topiramate: Fast facts

Mechanism: Potentiates GABA and inhibits glutamate receptor subtypes
FDA-approved for alcohol dependence: No
Dosing: 300 mg/d in divided doses
Effect: Decreases craving and drinking
Potential side effects: Metabolic acidosis, psychomotor slowing, dizziness, difficulty concentrating, paresthesia, weight loss, nephrolithiasis, hyperammonemia with concomitant use of valproic acid
Contraindications: None known other than hypersensitivity (as with all drugs)
Comments: Dose titration requires several weeks; avoid abrupt withdrawal; may reduce effectiveness of oral contraceptives

CASE CONTINUED: Implementing a treatment plan

You start Mr. G on oral naltrexone, 25 mg/d, and titrate to 100 mg/d. Although no optimum treatment duration has been established, you plan to follow NIAAA recommendations that Mr. G use naltrexone at least 3 months, with the possibility of continuing 1 year or longer if he responds well.¹

You schedule weekly visits for the first month to monitor for side effects and to make any necessary modifications in behavioral and pharmacologic treatment. You also continue escitalopram, 10 mg, which has successfully controlled Mr. G’s MDD symptoms.

Clinical Point

Medication has a role in treating alcohol dependence, but behavioral therapy remains important in substance abuse treatment as well

Medications for alcohol dependence generally have been studied as adjuncts to behavioral therapies. The COMBINE study of 1,383 alcohol-abstinent patients found naltrexone with medical management or cognitive-behavioral therapy alone to be equivalent in efficacy.¹⁹ The medical management provided a supportive environment, encouraged medication compliance, provided empathy to build a therapeutic relationship, and promoted self-help groups as an adjunct to treatment.³⁰ Thus, medication has a role in treating alcohol dependence, but behavioral therapy remains an important part of comprehensive substance abuse treatment.

When choosing medications, consider the agents’ clinically relevant differences:

Naltrexone and—less conclusively—topiramate have shown benefit for alcoholdependent patients starting treatment and for relapse prevention.
Acamprosate may help prevent relapse in abstinent patients.
Disulfiram remains a valid option in highly motivated patients with social support available to ensure medication adherence.

Because Mr. G is starting therapy after recent alcohol use, medications such as naltrexone and topiramate that have shown benefit early in treatment (in addition to relapse prevention) are preferred. Of these 2 drugs, naltrexone is the better choice for Mr. G—who is concerned about his work performance—because difficulty concentrating is a common side effect of topiramate. Oral naltrexone would be preferred as initial therapy for Mr. G because he has expressed comfort taking once-daily oral medication. The more expensive oncemonthly naltrexone depot formulation could be a second-line treatment if adherence becomes an issue.

Hypersensitivity is considered a contraindication for any medication. Mr. G tolerates well an initial dose of 25 mg/d, followed by increases to 50 mg and then 100 mg over several days. You titrate oral naltrexone to 100 mg/d—even though it is commonly prescribed at 50 mg/d—because recent evidence suggests efficacy and safety at the higher dosage.¹⁹

Related resources

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. www.niaaa.nih.gov/Publications/EducationTrainingMaterials/guide.htm.
American Society of Addiction Medicine. www.asam.org.
American Academy of Addiction Psychiatry. www.aaap.org.

Drug brand names

Acamprosate • Campral
Disulfiram • Antabuse
Escitalopram • Lexapro
Naltrexone, oral • ReVia
Naltrexone, extended-release • Vivitrol
Topiramate • Topamax
Valproic acid • Depakote

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.