Harm Reduction in Alcohol Use Disorder: Lessons From Sex Ed

This transcript has been edited for clarity.
Matthew F. Watto, MD: Welcome back to The Curbsiders . I'm Dr Matthew Frank Watto, here with my great friend and America's primary care physician, Dr Paul Nelson Williams. We had an awesome episode with Dr Stephen Holt and our addiction medicine crew, where we had a higher-level focus on medications for alcohol use disorder (AUD), mainly in the outpatient setting.
Paul, I think it's important to start off by saying that when we were young people coming up in this field, abstinence was pretty much the only approach in the treatment of AUD. The attitude was that if your patient was unable to reach absolute abstinence, you were a failure. We were also probably calling it "alcoholism" at the time.
But now, I think we're starting to take a more realistic, patient-centered, and evidence-based approach by recognizing that abstinence is not realistic for everybody. Instead, just a reduction in alcohol use can improve outcomes, including mortality. You really have to meet the patient where they are in the process.
And yes — for many patients, achieving complete abstinence would be most optimal for their overall health, but it may not be in the cards for them, and a reduction in use is worth shooting for. Anything to say about that, Paul?
Paul N. Williams, MD: It's all true. I think keeping things patient-centered is always important. We also need to recognize that even if the patient's goal is abstinence, it's really hard. These medications are effective but they're far from perfect. Accept that there may be returns to use and that you may not be able to achieve complete abstinence; be okay with that outcome and support the patient throughout the process. It's critical to avoid viewing it as a treatment failure, regardless of what your patient's goals might be.
Watto: We have three FDA-approved medications: Naltrexone (oral or intramuscular), disulfiram, and acamprosate. Paul, I was not familiar with targeted therapy. I thought you had to take these medications every day or once a month. Teach me something, Paul.
Williams: With AUD, there are often triggers of alcohol use, and often patients can anticipate what these triggers might be. On the episode we talked about Thanksgiving dinner — where we know an uncle's going to get us angry — or the anniversary of a loved one's death or being in a social situation. There are times when someone will know and recognize that they're going to be more likely to drink alcohol. So rather than being on chronic medication, patients can take medications in advance of whatever this occasion might be to help reduce their potential for use.
That can be done with naltrexone — the Sinclair Method — and it sounds like the data are especially good for nalmefene, but it's a European medication that is not approved in the United States. Dr Holt and our colleague, Carolyn Chan, also mentioned doing this with disulfiram as well.
This method of taking medication in anticipation of a known trigger — maybe a day or two before — can help patients be less likely to drink alcohol during that time, and can help them avoid all the burdens and hassles that come with being on a chronic medication. It's a neat technique that is not used as commonly as it could be, at least in my experience.
Watto: It sounded like Dr Holt advises patients to start the medication a couple days before the known trigger and to continue using the medication until they feel like things are settled again.
But Paul, Dr Holt loves disulfiram — I was shocked! I did not know this about him, and I thought no one was using disulfiram anymore. Have you prescribed it, and did you know that it was still "in vogue"?
Williams: I have prescribed it, but I don't know if it's "in vogue." It's got a bad reputation and it's not necessarily my first line, but Dr Holt has a lot of enthusiasm for it and he makes a really interesting point.
He brought up the fact that the studies that looked at disulfiram were randomized, double-blinded control trials. However, if you're a participant who believes that what you're taking (placebo or not) might make you deathly ill when you drink alcohol, that potential of severe illness will inevitably change patient behavior, regardless of what treatment arm they fall into. That kind of defeats the purpose of studying the efficacy of disulfiram in comparison to placebo. But when you actually look at the results of open-label trials — where patients knew what treatment arm they were randomized into and participants receiving the placebo knew there wasn't a real threat of severe illness — there's good evidence for disulfiram's efficacy in an observed setting.
Dr Holt had a lot of personal success with disulfiram, so he was a big advocate for it. Our conversation certainly made me more inclined to prescribe it than I had been prior to the episode, but it's probably still not my first choice.
Watto: I thought that was a really smart point about how, typically, randomized, blinded trials are our gold standard, but in this case the placebo becomes very strong in a blinded setting when the patient is not sure whether their treatment will cause them to get horribly ill if they drink.
The standard dose of disulfiram is 250 mg. If patients don't become sick after drinking at that dose, Dr Holt said he would up the dose to 500 mg. That usually isn't common, but some patients just don't have that typical response at the standard dose and must be metabolizing alcohol some other way. However, most patients need to be really careful. Patients should avoid all alcohol-containing products, including mouthwash, vanilla extract, and many types of aftershave.
The contraindications for disulfiram include:
Pregnancy
Cognitive impairment, as patients may not remember if they took their medications or not
Severe cardiovascular disease, as a reaction can cause ischemia
Advanced liver disease (eg, cirrhosis with Child-Pugh class B or C)
Dr Holt would still use disulfiram for patients with mild cirrhosis who are considered Child-Pugh class A but recommends following the liver closely. I looked disulfiram up on LiverTox and there is some concern about acute medication-induced hepatitis that could be really serious. So, if a patient already has a sick liver at baseline, you probably don't want to give them this medication.
Williams: Beyond the fact that I feel like this medication sometimes feels a little bit moralistic or kind of punitive for people who are drinking, as though it's just a sort of built-in punishment, my larger concern with prescribing disulfiram is the potential for hepatotoxicity. However, that may have been overstated in my brain.
Watto: If I had a patient without contraindications, I would at least have a conversation to see if it's the right person, because it does take drinking off the table. Even if they're having cravings, they know they'll get violently ill if they drink and they don't want to end up in an ER for IV fluids because they're vomiting. I think it works, but it requires a little bit of a tricky conversation. But I do think this episode made me reconsider disulfiram as an agent to prescribe.
Williams: It goes back to your original point of shared decision-making: We need to make sure we're making informed decisions together and matching treatments with patients' goals. If a patient is interested in disulfiram after a detailed conversation, I would not try to talk them out of it. I'm more inclined to reach for it now after speaking with Dr Holt.
Watto: So, Paul, what off-label medications might listeners consider for AUD treatment?
Williams: There's a bazillion, and there have been lots of small studies looking at different options and combinations. If you're unable to use the FDA-approved medications, topiramate is the one medication Dr Holt would reach for. It's even highlighted in the Veterans Affairs/Department of Defense guidelines.
It can be a tricky medication because it has to be titrated slowly; we're talking about increments of 25 mg. As such, you have to have a patient who can follow directions, is committed to taking a medication, and is fairly well organized, which is not always the case when someone has an underlying AUD. There's also a lot of intolerable side effects for a lot of folks; patients might experience somnolence and paresthesias, so you have to be a little bit cautious with those. However, topiramate does have evidence to support its use.
We talk a good bit about gabapentin as well, Matt. It's something that we've all prescribed for a million different reasons. Dr Holt is a fan of it, specifically for alcohol withdrawal, but also there is some evidence for its use with AUD. It seems helpful, especially in combination with, say, naltrexone. I'm more inclined to reach for that.
We touched briefly on baclofen, and I've known people who have been enthusiastic about it as an option. There is evidence to support its use, but it's not one we talked too much about this episode.
Watto: We also talked a little bit about combination therapy. There's not really strong evidence for it. I know you mentioned that sometimes you might use naltrexone and gabapentin together, but the evidence overall for something like naltrexone and acamprosate didn't seem to pan out.
Williams: It's not well supported — correct.

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