Joanne is a 50 year-old woman who has had difficulty cutting back on drinking. She has been drinking 1-3 glasses of wine a night for decades. She has cravings for wine and continues to drink despite waking up hungover and showing up late to work. Joanne recalls daytime anxiety and tremulousness that both seem to go away when she has her first glass of wine later in the day. Some of her friends have distanced themselves from her because of her drinking. Joanne has a BMI of 31 and a history of kidney stones. After years of discomfort from arthritis in her left knee, Joanne is planning to get a knee replacement this month.
Joanne asks you, as her primary care clinician, what she can take (medication-wise) to help her cut back on drinking. She’s not ready to stop entirely. The alcohol helps her calm down after a long day at work and reduces her anxiety and rumination about the things she needs to do the next day. Right now, Joanne drinks two glasses of wine a night and 4-5 glasses of wine on Fridays.
What medications can help Joanne reduce her drinking?
- Naltrexone
- Acamprosate
- Disulfiram
- Topiramate
- Gabapentin
- Semaglutide
Naltrexone is the first-line recommended medication for people with alcohol use disorder (AUD) who want to cut down on drinking (as reviewed in a previous PsychSnap). Naltrexone is not appropriate for Joanne given her upcoming surgery and likely need for opioid medications.
The other two FDA approved medications for alcohol use disorder are acamprosate and disulfiram. Neither is appropriate for Joanne, because she wants to decrease her drinking, not stop drinking entirely. Acamprosate is most effective for patients whose goal is to stop drinking and who can take two pills three times a day. In patients with a goal of abstinence, the number needed to treat (NNT) to prevent one person from returning to any drinking was 11 for acamprosate and 18 for naltrexone, according to a 2023 systemic review and meta analysis in JAMA Psychiatry* (McPheeters 2023). Joanne‘s desire to keep drinking makes disulfiram a terrible choice, as it acts as a pharmacologic punishment that will make her sick if she drinks while taking it.
Topiramate is not FDA approved for AUD, but is recommended right after naltrexone in the Veterans Affairs (VA) treatment guidelines. Earlier data showed a reduction of cravings and a 2024 randomized, controlled trial found topiramate to be as effective as naltrexone in reducing heavy alcohol use and possibly superior to it in reducing total alcohol consumed (Morley 2024). While earlier VA trials used a high dose of topiramate (150mg BID) which is hard to achieve in practice due to side effects, the 2024 trial used the lower dose of topiramate 100mg BID.
Topiramate is better tolerated with fewer cognitive side effects when it is titrated slowly. Consider this slow titration schedule over 6-8 weeks: topiramate 25mg bedtime x1 week, 25mg BID x 1 week, 25mg morning/50mg bedtime x1 week, then 50mg BID x1 week. Depending on how well the patient tolerates the 50mg BID dose, continue dose increases of 25-50mg weekly to a target dose of topiramate 100mg BID. Monitor for the paresthesias, cognitive changes, and changes in taste. Relative contraindications to topiramate include a history of kidney stones (which Joanna has!) and glaucoma. Absolute contraindications to topiramate include pregnancy and a ketogenic diet (which increases the chance of metabolic acidosis or stones). Topiramate also reduces the serum concentrations of hormonal contraceptives and requires renal dosing for patients with a GFR<70.
Gabapentin is not FDA-approved for AUD. It has been shown to reduce alcohol cravings and heavy drinking at doses of gabapentin 300-600mg TID, with higher doses being more effective (Mason 2014). The data for gabapentin is mixed, however, and side effects like dizziness and cognitive slowing along with concerns around possible misuse limit its use (Weresch 2021). One RCT attempted to carve out a patient population that might benefit from gabapentin, specifically patients with AUD and a history of alcohol withdrawal. In this group (n=90), gabapentin 400mg TID reduced overall drinking and heavy drinking, with a NNT for abstinence of 8 compared to placebo (Anton 2020).
Given that Joanne’s history of kidney stones is a relative contraindication to topiramate, and that gabapentin can help comorbid anxiety (off-label), you discuss starting gabapentin 100mg when Joanne is getting ready for bed. After a few days, she can add another dose of gabapentin 100mg when she comes home from work to reduce her after-work anxiety that may be contributing to her drinking. Joanne says she’s interested in the gabapentin trial. She also asks you if something like Wegovy could help with weight loss and decrease her alcohol cravings.
What do we know right now about GLP-1 receptor agonists in the treatment of AUD?
GLP-1 receptor agonists are not FDA-approved for AUD treatment. However, trials are emerging (and ongoing) that show that GLP-1 agonists (GLP-1s) may reduce cravings, alcohol consumption and the development of alcohol-related problems. A short podcast episode from ASAM does a nice job of summarizing the literature on GLP-1s in AUD (ASAM 2024 featuring Dr. Stephanie Weiss).
Semaglutide and other GLP-1s are long-acting versions of the incretin GLP that impact the GI tract, pancreas, and brain. High-doses of GLP-1s like those used in obesity treatment also affect the reward and satiety pathways in the brain, which may explain the preclinical and animal studies showing that GLP-1s reduce alcohol intake and high-risk alcohol intake behavior. Similarly, cohort studies, medical records-based studies, and anecdotal evidence from patients with AUD suggest that GLP-1 use reduces alcohol consumption.
In a 2024 systematic review, researchers examined the interaction between GLP-1 receptor agonists and alcohol intake in people with AUD. The impact of GLP-1s on alcohol consumption across the studies was heterogeneous, and the authors concluded that rigorous RCTs were needed to verify any promising results (Subhani 2024). In February 2025, JAMA Psychiatry published the results of a phase 2, double-blind, randomized controlled trial that compared low-dose semaglutide to placebo over 9 weeks in 48 non-treatment-seeking adults with AUD. In this small sample, GLPs reduced alcohol consumption and cravings relative to placebo and also reduced cigarette use in a subgroup analysis (Hendershot 2025). Larger randomized clinical trials of GLP-1s for AUD are needed.
Returning to Joanne, you share the current landscape of GLP use for AUD, including the lack of large RCTs or an FDA indication. You also note that she may be a good candidate for a GLP-1 agonist for her elevated BMI, and you are happy to discuss the medication further for this indication. You also share that you can re-discuss naltrexone, the first line FDA-approved medication that can help reduce drinking, once she has recovered from her knee surgery.
*Of note, some clinicians worry about medications for AUD (MAUD) being ineffective. The NNTs for MAUD compare well with those for other meds we use often in primary care for diabetes, asthma, or depression (Busch 2025).
Key Points
- The FDA-approved medications for AUD are naltrexone, acamprosate, and disulfiram, with naltrexone having the best evidence for people who want to reduce use or stop entirely.
- Topiramate and gabapentin can help to reduce heavy drinking, but are not FDA approved for this indication
- There is emerging evidence that GLP-1s reduce alcohol cravings and consumption. If using GLP-1s for patients with DM or obesity who also have AUD, monitor both their weight and their alcohol use.
Related PsychSnaps:
“What medication can help this patient drink less wine?” Era Kryzhanovskaya, Jan 2023.
“How do you help patients cut back on drinking?” Era Kryzhanovskaya, December 2023.
References:
Anton RF, Latham P, Voronin K, et al. Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial. JAMA Intern Med. 2020;180(5):728–736.
ASAM Practice Pearls Podcast, “GLP-1 Receptor Agonists Explained: Their Potential Role in Addiction Treatment.” Published January 22, 2025.
Busch AB, Greenfield SF, Huskamp HA. Expanding Alcohol Use Disorder Medications in Primary Care. JAMA Intern Med. Published online March 03, 2025.
Hendershot CS, Bremmer MP, Paladino MB, et al. Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. Published online February 12, 2025.
Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014 Jan;174(1):70-7.
McPheeters M, O’Connor EA, Riley S, Kennedy SM, Voisin C, Kuznacic K, Coffey CP, Edlund MD, Bobashev G, Jonas DE. Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis. JAMA. 2023 Nov 7;330(17):1653-1665.
Morley KC, Kranzler HR, Luquin N, Jamshidi N, Adams C, Montebello M, Tremonti C, Dali G, Logge W, Baillie A, Teesson M, Trent R, Haber PS. Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial. Am J Psychiatry. 2024 May 1;181(5):403-411.
Subhani M, Dhanda A, King JA, Warren FC, Creanor S, Davies MJ, Eldeghaidy S, Bawden S, Gowland PA, Bataller R, Greenwood J, Kaar S, Bhala N, Aithal GP. Association between glucagon-like peptide-1 receptor agonists use and change in alcohol consumption: a systematic review. EClinicalMedicine. 2024 Nov 14;78:102920.
Weresch J, Kirkwood J, Korownyk CS. Gabapentin for alcohol use disorder. Can Fam Physician. 2021 Apr;67(4):269.
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