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.
There are limited studies that prove the efficacy of disulfiram. In a randomized trial comparing disulfiram, acamprosate, and naltrexone, patients treated with disulfiram had fewer heavy drinking days, lower rates of weekly alcohol consumption, and a longer period of abstinence compared to other medications.45 Additionally, a 2014 meta-analysis showed that in open-label studies, disulfiram was more beneficial in preventing alcohol consumption when compared with acamprosate, naltrexone, and placebo. This result was not seen in blinded studies.46 Disulfiram does not reduce alcohol cravings, and adherence is a significant issue. It is most effective between 2 and 12 months, when taken under supervised administration.47
Dosing and Formulations
Disulfiram is only available as a tablet. The recommended starting dose is up to 500 mg for the first 2 weeks. However, the maintenance dose can range from 125 to 500 mg daily.43 Patients must be abstinent from alcohol at least 12 to 24 hours prior to the initiation of disulfiram.25 A blood alcohol level can be obtained in order to confirm abstinence.25
Warnings, Precautions, and AEs
Disulfiram is contraindicated in patients with severe myocardial disease or coronary occlusion and severe hepatic impairment.43 Other contraindications are outlined in Table 3.
It should never be used in patients receiving alcohol, metronidazole, or alcohol-containing preparations.
Common AEs include somnolence, a metallic after-taste, and peripheral neuropathy.43 Patients should be informed that they could experience a disulfiram reaction with even small amounts of alcohol; all foods, drinks, and medications containing alcohol should be avoided. Due to the potential of disulfiram potential to cause hepatotoxicity, liver transaminases should be monitored at baseline, 2 weeks after initiation, and monthly for the first 6 months of therapy, and every 3 months thereafter (Table 2).25
Off-Label Pharmacotherapies
Topiramate
Although not approved for AUD, topiramate has been used off-label for this indication as it has proven efficacy in clinical trials.48-56 While its mechanism of action for AUD is unclear, it has been theorized that topiramate antagonizes glutamate receptors, thereby reducing dopamine release in the nucleus accumbens upon alcohol consumption, and potentiates the inhibitory neurotransmitter GABA.50,51,57-60
In clinical trials, topiramate has demonstrated significant efficacy in reducing cravings, the risk of relapse, and the number of drinks consumed daily, while increasing abstinence.51,53,60 Batki and colleagues report that the administration of topiramate in veterans with co-occurring AUD and PTSD reduced alcohol consumption, cravings, and the severity of their PTSD symptoms.61
Dosing and Formulations
Topiramate is available in a number of formulations; however, only the immediate-release formulation is recommended for the treatment of AUD. The extended-release formulation is contraindicated in the setting of alcohol consumption and is therefore not used for the treatment of AUD.62 Doses should be initiated at 25 mg daily and can be titrated in 25 to 50 mg weekly increments. To minimize AEs and to reduce the risk of patients discontinuing therapy, the dose may be slowly titrated over 8 weeks.53,59 An effective dose can range from 75 to 300 mg in divided doses; however, AEs often limit the tolerability of increased doses.48,50,63,64 The VA/DoD Practice Guideline for the Management of Substance Use Disorders recommends titrating topiramate to a target dose of 100 mg twice daily.65
