Jasmine Carpenter is a Mental Health Clinical Pharmacy Specialist; Danielle LaPrad and Yewande Dayo are Pharmacy Practice Residents; and Shannon DeGrote is a Clinical Pharmacy Specialist, all at the Washington DC VA Medical Center. Kasraie Williamson is a Pharmacy Resident at Memorial Regional Hospital in Hollywood, Florida. Correspondence: Jasmine Carpenter (jasmine.carpenter@va.gov)
Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
The FDA approved acamprosate for the treatment of AUD in 2004, and it is also considered a first-line agent for AUD by the VA.20 It is approved for the maintenance of abstinence from alcohol use and is most efficacious when initiated in patients who are abstinent prior to treatment.29,36 Patients with AUD typically have a disruption in the balance between the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), and the excitatory neurotransmitter, glutamate. While its mechanism of action remains unknown, acamprosate is thought to increase the activity of GABA and to decrease the activity of glutamate at the N-methyl-D-aspartate (NMDA) receptors in the central nervous system. In essence, it is thought to restores the balance between GABA and glutamate in patients with AUD.36
Acamprosate has been found to effectively prevent relapse. Three randomized, double-blind, placebo-controlled European clinical trials evaluated the efficacy of acamprosate in combination with psychotherapy. The results demonstrated that patients taking acamprosate had longer durations of abstinence compared with that of placebo, improved rates of complete abstinence, and a prolonged time to first drink.37-39 A meta-analysis evaluated the use of acamprosate in AUD showed that acamprosate was more effective at maintaining abstinence in patients who had been abstinent prior to the initiation of therapy.29 These patients also had better abstinence rates if they had been abstinent for a longer duration prior to treatment initiation.30 Studies also showed that acamprosate significantly assisted with maintaining abstinence, improved rates of abstinence, and led to more days of abstinence.40,41 Of note, there also have been studies that have shown no significant benefit with acamprosate compared with placebo in the treatment of AUD.42
Dosing and Formulations
Acamprosate is available as a 333 mg delayed-release tablet. The recommended dose is 666 mg 3 times daily.36 The dose can be decreased to 333 mg 3 times a day in patients with moderate renal impairment (CrCl-30-50 mL/min).
Since acamprosate has been proven more effective in patients who are abstinent prior to initiation, acamprosate is typically initiated 5 days following alcohol cessation.25 However, it may be safely administered with alcohol and can continue to be administered in the event of a relapse.36
Warnings, Precautions, and AEs
Acamprosate is safe to use in patients with hepatic and mild-to-moderate renal impairment; however, it is contraindicated in patients with severe renal impairment (creatinine clearance [CrCl] ≤ 30 mL/min).36 Serum creatinine levels should be monitored at baseline and during treatment.
Acamprosate has a number of related AEs. The most common is diarrhea. Less common AEs include insomnia, anxiety, and depression. Due to its possible potential to increase suicidality, HCPs should monitor for the emergence of mood changes.36
Disulfiram
Disulfiram is an aldehyde dehydrogenase inhibitor that is FDA approved for the management of AUD.43 When ingested, ethanol is typically metabolized to acetaldehyde, which is further metabolized to acetic acid by aldehyde dehydrogenase.44 Disulfiram inhibits aldehyde dehydrogenase, leading to a rapid accumulation of acetaldehyde within the plasma (outlined in Figure 2).
An elevation in the acetaldehyde results in a toxic reaction, which is known as a disulfiram-alcohol reaction characterized by flushing, nausea, thirst, palpitations, chest pain, vertigo, and hypotension. This reaction usually begins within 10 to 30 minutes after alcohol ingestion and can last for several hours.25 Due to this unpleasant reaction, disulfiram should only be used in patients whose goal is to remain abstinent. This agent would not be ideal in patients who only aim to reduce heavy drinking.
