Treating alcohol dependence: When and how to use 4 medications

Naltrexone

Naltrexone is a μ-opioid receptor antagonist thought to reduce alcohol’s reinforcing effects by interfering with β-endorphin pathways. It is indicated for treating alcohol dependence and has been shown to reduce relapse and number of drinking days in alcohol-dependent patients (Table 2).¹⁵

Naltrexone also has reduced alcohol consumption in healthy volunteers, social drinkers, and other nondependent drinkers.¹⁶ Its effect may have a genetic component, as suggested by greater benefit in persons with a family history of alcoholism.¹⁷

Efficacy. Most studies investigated naltrexone as part of a comprehensive treatment program that included behavioral therapies.¹⁸ Recently, the randomized, placebo-controlled Combining Medications and Behavioral Interventions (COMBINE) study found that using either naltrexone or behavioral therapy improved abstinence, and combing naltrexone with behavioral therapy was not more effective than either treatment alone.¹⁹

Administration. Oral naltrexone is usually started at 25 mg and increased over 2 to 3 days to 50 or 100 mg/d. The standard dose is 50 mg/d, although the COMBINE study reported efficacy at 100 mg/d.¹⁹

Oral naltrexone is most helpful for patients who adhere to 70% to 90% of the medication.²⁰ The extended-release form (a 380-mg IM dose given every 4 weeks) provides an option to monitor adherence.²¹

Side effects. Naltrexone toxicity can cause hepatocellular injury. Do not administer this drug to patients with acute hepatitis or end-stage liver disease. When prescribing naltrexone, check patients’ liver function monthly for the first 3 months, then once every 3 months thereafter.²² Less serious, common side effects include nausea, myalgia, and headache.

Naltrexone antagonizes opioid receptors and causes withdrawal symptoms in patients who are physically dependent on opioids. Therefore, do not give naltrexone to patients who require opioids for chronic pain. If your patient is using an opioid but could switch to other pain medication, discontinue the opioid for at least 7 days and consider a urine toxicology or naltrexone challenge before starting naltrexone.

Urine drug tests are inexpensive and easy to use but have limitations. Many standard “dipsticks” will detect heroin, morphine, and codeine but not oxycodone, hydrocodone, or other synthetic opioids. Specific tests are available to detect oxycodone, hydrocodone, hydromorphone, buprenorphine, and methadone. Some synthetic opioids (such as fentanyl) remain difficult to detect, however, because of their low concentration and rapid metabolism.

Table 2

Naltrexone: Fast facts

Acamprosate

Acamprosate is structurally similar to gamma-aminobutyric acid (GABA) and is thought to inhibit the glutamatergic system. This attenuation by acamprosate reduces the glutamatergic hyperactivity normally seen after chronic alcohol exposure.

Acamprosate is indicated for relapse prevention in patients with alcohol dependence who have stopped drinking (Table 3). Multiple randomized studies have demonstrated its efficacy in improving abstinence rates as compared with placebo.^23,24 Other studies, however, failed to show improved abstinence with acamprosate.²⁵ Some of the negative studies included patients who recently relapsed or had only a few days of abstinence before starting acamprosate.^19,26 Therefore, acamprosate might be most effective when used to maintain abstinence and less effective—if at all—to initiate abstinence.

Administration. Acamprosate is available in 333-mg tablets, with a recommended dosage of 666 mg tid. Side effects tend to be transient and mild. Reduce the dose to 333 mg tid for patients with moderate renal insufficiency (creatinine clearance [CrCl] 30 to 50 mL/min), and do not use acamprosate in patients with severe renal insufficiency (CrCl

In some placebo-controlled studies, patients taking acamprosate reported more frequent suicidal thoughts and attempts compared with patients taking placebo.²⁷ These events were extremely rare, and no direct relationship with acamprosate therapy has been established. Nonetheless, monitor patients for depression and suicidal thoughts during acamprosate therapy.

Table 3

Acamprosate: Fast facts

Topiramate

Topiramate potentiates GABA and inhibits excitatory glutamate transmission—properties believed to lead to decreased dopamine release at the nucleus accumbens in response to alcohol consumption. Although topiramate is not FDA-approved for alcohol dependence, limited data comparing this anticonvulsant with placebo have shown a reduction in drinking and increased abstinence (Table 4).^28,29