A 46-year-old woman comes to the office for follow-up after an episode of alcoholic pancreatitis. She was hospitalized 4 weeks ago for abdominal pain and concurrently underwent treatment with benzodiazepines for alcohol withdrawal. Prior to hospitalization, the patient was drinking 3 L of boxed wine daily; however, she has remained abstinent since discharge. She is interested in medication for her alcohol use disorder, but lives alone and is worried that her cravings will overwhelm her self control. A medication with which of the following mechanisms of action would be most effective in this patient?
In addition to psychosocial interventions (eg, motivational interviewing, Alcoholics Anonymous), several medications are available to treat alcohol use disorder, including naltrexone and acamprosate. Naltrexone blocks the mu-opioid receptor and inhibits the rewarding and reinforcing effects of alcohol, helping to reduce cravings and improving motivation to quit. The long-acting depot form (given as monthly injections) is useful for patients at risk for nonadherence with daily administration. Acamprosate, another abstinence-promoting drug, works by modulating glutamate neurotransmission at the N-methyl-D-aspartate receptor.
(Choice A) The aldehyde dehydrogenase inhibitor disulfiram is considered a second-line treatment for alcohol use disorder because of poorer efficacy (effectiveness depends on supervised administration). When alcohol is ingested by a patient taking disulfiram, acetaldehyde accumulates and causes unpleasant adverse effects (eg, nausea, vomiting, flushing, sweating, headache).
(Choice B) Antagonism at postsynaptic dopamine receptors is the mechanism of action of antipsychotic medications. Antipsychotics are not effective in treating alcohol use disorder.
(Choice D) Varenicline acts as a partial neuronal nicotinic receptor agonist and prevents the nicotine stimulation of the mesolimbic dopamine system associated with nicotine addiction.
(Choice E) Serotonin reuptake inhibition is the mechanism of action of selective serotonin reuptake inhibitor antidepressants. Although they have shown some efficacy in reducing alcohol use in patients with alcohol use disorder who have comorbid depression, they are not useful for alcohol cessation in patients without comorbid depression.
Educational objective:
The opioid antagonist naltrexone is a first-line pharmacotherapy for moderate-to-severe alcohol use disorder, and works by preventing the reinforcing effects of alcohol use.