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.
Ondansetron is approved for both prophylactic and therapeutic use as an antiemetic agent for chemotherapy and anesthesia-induced nausea and vomiting.77As a highly selective and competitive 5-HT3 receptor antagonist, ondansetron has demonstrated efficacy in reducing serotonin-mediated dopaminergic effects in AUD.78,79 The lowering of these dopaminergic effects is associated with a reduction in alcohol-induced gratification and consumption.
In a 12-week, randomized controlled trial, 271 patients diagnosed with AUD received ondansetron twice daily or placebo, combined with weekly cognitive behavioral therapy (CBT). There was a statistically significant decrease in alcohol consumption in patients treated with ondansetron compared with those who received placebo. Additionally, ondansetron was superior to placebo for increasing the percentage and total amount of days abstinent.80These results were primarily observed in participants diagnosed with early-onset AUD (defined as onset at 25 years or younger), which may suggest the presence of genetically predisposed serotonin dysfunctions.80,81In contrast, there were no significant differences observed in participants with late-onset AUD (onset after age 25 years) in either study group.80
Dosing and Formulations
Given its modest efficacy for the treatment of AUD, ondansetron has demonstrated clinical benefits at doses of 0.001 to 0.016 mg/kg twice daily. Additionally, 1 study reported that low-dose ondansetron (0.25 mg twice daily) was effective in reducing alcohol consumption when compared with placebo or high-dose ondansetron, which was considered 2 mg twice daily.82
Warnings, Precautions, and AEs
The most commonly reported AEs with ondansetron include fatigue, headache, anxiety, and serotonin syndrome when used concomitantly with other serotonergic agents.77 Also, serious cardiovascular complications, such as QTc prolongation, angina pectoris, atrial fibrillation, and arrhythmias have been observed with IV administration.77,81,83 Consequently, patients with electrolyte imbalances (eg, hypokalemia, hypomagnesemia), a history of congestive heart failure, or concomitant medications associated with QTc prolongation, should be monitored with an electrocardiogram (ECG) or switched to another agent.77
Treatment Approach with AUD Pharmacotherapy
There is insufficient evidence to support the use of 1 medication for AUD over the others.16,46,84 Instead, the choice of therapy largely depends on the patient’s comorbidities, renal and hepatic function, and on the patient’s established goals, whether abstinence or reduction in alcohol consumption (Table 4).
Some HCPs may opt to combine AUD pharmacotherapy, but there is limited evidence on this treatment approach. Despite the inconsistent data on the medications used for AUD and the various treatment approaches, many of the large studies and meta-analyses support the utilization of these agents in patients with AUD.
There is much debate over the appropriate duration of treatment for AUD pharmacotherapy. It is recommended that patients remain on these medications for at least 3 months. Pharmacotherapy can be continued for 6 to 12 months as the risk for relapse is highest during this time frame.85,86 The National Institute for Health and Care Excellence guidelines recommend discontinuing AUD pharmacotherapy if alcohol consumption persists 4 to 6 weeks after initiation.86
Comorbid Liver Disease
Due to the negative effects of heavy alcohol consumption on the liver, patients with AUD may develop liver disease. Health care providers should be aware of the appropriate pharmacotherapy options for patients with comorbid liver disease. Acamprosate is mostly excreted unchanged by the kidneys, therefore is an option for patients with liver disease whose goal is complete abstinence. Topiramate is another option for use in patients with liver impairment. Unlike acamprosate, topiramate would be a better option in patients who may not completely abstain from alcohol consumption but would like to decrease the amount of heavy drinking days.87
