After detoxification, psychosocial therapy either in intensive inpatient or in outpatient rehabilitation programs serves as the primary treatment for alcohol dependence. Other psychiatric problems, most commonly depressive or anxiety disorders, often coexist with alcoholism and, if untreated, can contribute to the tendency of detoxified alcoholics to relapse. Treatment for these associated disorders with counseling and drugs can help decrease the rate of relapse for alcoholic patients.
Three drugs—disulfiram, naltrexone, and acamprosate—have FDA approval for adjunctive treatment of alcohol dependence.
Naltrexone, a relatively long-acting opioid antagonist, blocks μ-opioid receptors (see Chapter 31). Alone and in combination with behavioral counseling, naltrexone has been shown in a number of short-term (12to 16-week), placebo-controlled trials to reduce the rate of relapse to either drinking or alcohol dependence and to reduce craving for alcohol, especially in patients with high rates of naltrexone adherence. Naltrexone is approved by the FDA for treatment of alcohol dependence. Nalmefene, another opioid antagonist, appears to have similar effects in alcohol-use disorder but is not yet approved by the FDA for this indication.
Naltrexone is generally taken once a day in an oral dose of 50 mg for treatment of alcoholism. An extended-release formulation administered as an intramuscular injection once every 4 weeks is also effective. The drug can cause dose-dependent hepatotoxicity and should be used with caution in patients with evidence of abnormalities in serum aminotransferase activity. The combination of naltrexone plus disulfiram should be avoided, since both drugs are potential hepatotoxins. Administration of naltrexone to patients who are physically dependent on opioids precipitates an acute withdrawal syndrome, so patients must be opioid-free before initiating naltrexone therapy. Naltrexone also blocks the therapeutic analgesic effects of usual doses of opioids.
Acamprosate has been used in Europe for a number of years to treat alcohol dependence and is approved for this use by the FDA. Like ethanol, acamprosate has many molecular effects including actions on GABA, glutamate, serotonergic, noradrenergic, and dopaminergic receptors. Probably its best-characterized actions are as a weak NMDA-receptor antagonist and a GABAA-receptor activator. In European clinical trials, acamprosate reduced short-term and long-term (more than 6 months) relapse rates when combined with psychotherapy. However, in a large American trial that compared acamprosate with naltrexone and with combined acamprosate and naltrexone therapy (the COMBINE study), acamprosate did not show a statistically significant effect alone or in combination with naltrexone.
Acamprosate is administered as one or two enteric-coated 333-mg tablets three times daily. It is poorly absorbed, and food reduces its absorption even further. Acamprosate is widely distributed and is eliminated renally. It does not appear to participate in drug-drug interactions. The most common adverse effects are gastrointestinal (nausea, vomiting, diarrhea) and rash. It should not be used in patients with severe renal impairment.