CLINICIAN SUPPORT MATERIALS
Three oral medications (naltrexone, acamprosate, and disulfiram) and one injectable medication (extended-release injectable naltrexone) are currently approved for treating alcohol dependence. They have been shown to help patients reduce drinking, avoid relapse to heavy drinking, achieve and maintain abstinence, or gain a combination of these effects. As is true in treating any chronic illness, addressing patient adherence systematically will maximize the effectiveness of these medications (see "Supporting Patients Who Take Medications for Alcohol Dependence," page 17).
When should medications be considered for treating an alcohol use disorder?
All approved drugs have been shown to be effective adjuncts to the treatment of alcohol dependence. Thus, consider adding medication whenever you're treating someone with active alcohol dependence or someone who has stopped drinking in the past few months but is experiencing problems such as craving or slips. Patients who have previously failed to respond to psychosocial approaches alone are particularly strong candidates.
Must patients agree to abstain?
No matter which alcohol dependence medication is used, patients who have a goal of abstinence, or who can abstain even for a few days prior to starting the medication, are likely to have better outcomes. Still, it’s best to determine individual goals with each patient. Some patients may not be willing to endorse abstinence as a goal, especially at first. If a patient with alcohol dependence agrees to reduce drinking substantially, it’s best to engage him or her in that goal while continuing to note that abstinence remains the optimal outcome.
A patient's willingness to abstain has important implications for the choice of medication. Most studies on effectiveness have required patients to abstain before starting treatment. A study of oral naltrexone, however, demonstrated a modest reduction in the risk of heavy drinking in people with mild dependence who chose to cut down rather than abstain.17 A study of injectable naltrexone suggests that it, too, may reduce heavy drinking in dependent patients who are not yet abstinent, although it had a more robust effect in those who abstained for 7 days before starting treatment18 and is only approved for use in those who can abstain in an outpatient setting before treatment begins. Acamprosate, too, is only approved for use in patients who are abstinent at the start of treatment. And disulfiram is contraindicated in patients who wish to continue to drink, because a disulfiram-alcohol reaction occurs with any alcohol intake at all.
Which of the medications should be prescribed?
Which medication to use will depend on clinical judgment and patient preference. Each has a different mechanism of action. Some patients may respond better to one type of medication than another.
Mechanism: Naltrexone blocks opioid receptors that are involved in the rewarding effects of drinking alcohol and the craving for alcohol. It's available in two forms: oral (Depade®, ReVia®), with once daily dosing, and extended-release injectable (Vivitrol®), given as once monthly injections.
Efficacy: Oral naltrexone reduces relapse to heavy drinking, defined as 4 or more drinks per day for women and 5 or more for men.19,20 It cuts the relapse risk during the first 3 months by about 36 percent (about 28 percent of patients taking naltrexone relapse versus about 43 percent of those taking a placebo).20 Thus, it is especially helpful for curbing consumption in patients who have drinking "slips." It is less effective in maintenance of abstinence.19,20 In the single study available when this Guide update was published, extended-release injectable naltrexone resulted in a 25 percent reduction in the proportion of heavy drinking days compared with a placebo, with a higher rate of response in males and those with lead-in abstinence.18
Mechanism: Acamprosate (Campral®) acts on the GABA and glutamate neurotransmitter systems and is thought to reduce symptoms of protracted abstinence such as insomnia, anxiety, restlessness, and dysphoria. It's available in oral form (three times daily dosing).
Efficacy: Acamprosate increases the proportion of dependent drinkers who maintain abstinence for several weeks to months, a result demonstrated in multiple European studies and confirmed by a meta-analysis of 17 clinical trials.21 The meta-analysis reported that 36 percent of patients taking acamprosate were continuously abstinent at 6 months, compared with 23 percent of those taking a placebo. More recently, two large U.S. trials failed to confirm the efficacy of acamprosate,22,23 although secondary analyses in one of the studies suggested possible efficacy in patients who had a baseline goal of abstinence.23 A reason for the discrepancy between European and U.S. findings may be that patients in European trials had more severe dependence than patients in U.S. trials,21,22 a factor consistent with preclinical studies showing that acamprosate has a greater effect in animals with a prolonged history of dependence.24 In addition, before starting medication, most patients in European trials had been abstinent longer than patients in U.S. trials.25
Mechanism: Disulfiram (Antabuse®) interferes with degradation of alcohol, resulting in accumulation of acetaldehyde which, in turn, produces a very unpleasant reaction including flushing, nausea, and palpitations if the patient drinks alcohol. It's available in oral form (once daily dosing).
Efficacy: The utility and effectiveness of disulfiram are considered limited because compliance is generally poor when patients are given it to take at their own discretion.26 It is most effective when given in a monitored fashion, such as in a clinic or by a spouse.27 (If a spouse or other family member is the monitor, instruct both monitor and patient that the monitor should simply observe the patient taking the medication and call you if the patient stops taking the medication for 2 days.) Some patients will respond to self-administered disulfiram, however, especially if they're highly motivated to abstain. Others may use it episodically for high-risk situations, such as social occasions where alcohol is present.
How long should medications be maintained?
The risk for relapse to alcohol dependence is very high in the first 6 to 12 months after initiating abstinence and gradually diminishes over several years. Therefore, a minimum initial period of 3 months of pharmacotherapy is recommended. Although an optimal treatment duration hasn't been established, it isn't unreasonable to continue treatment for a year or longer if the patient responds to medication during this time when the risk of relapse is highest. After patients discontinue medications, they may need to be followed more closely and have pharmacotherapy reinstated if relapse occurs.
If one medication doesn't work, should another be prescribed?
If there's no response to the first medication selected, you may wish to consider a second. This sequential approach appears to be common clinical practice, but currently there are no published studies examining its effectiveness. Similarly, there is not yet enough evidence to recommend a specific ordering of medications.
Is there any benefit to combining medications?
A large U.S. trial found no benefit to combining acamprosate and naltrexone.22 More broadly, there is no evidence that combining any of the medications to treat alcohol dependence improves outcomes over using any one medication alone.
Should patients receiving medications also receive specialized alcohol counseling or a referral to mutual help groups?
Offering the full range of effective treatments will maximize patient choice and outcomes, since no single approach is universally successful or appealing to patients. The different approaches—medications for alcohol dependence, professional counseling, and mutual help groups—are complementary. They share the same goals while addressing different aspects of alcohol dependence: neurobiological, psychological, and social. The medications aren't prone to abuse, so they don't pose a conflict with other support strategies that emphasize abstinence.
Almost all studies of medications for alcohol dependence have included some type of counseling, and it's recommended that all patients taking these medications receive at least brief medical counseling. In a recent large trial, the combination of oral naltrexone and brief medical counseling sessions delivered by a nurse or physician was effective without additional behavioral treatment by a specialist.22 Patients were also encouraged to attend support groups to increase social encouragement for abstinence. For more information, see "Supporting Patients Who Take Medications for Alcohol Dependence" on page 17 and "Should I recommend any particular behavioral therapy for patients with alcohol use disorders?" on page 31.