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Alcohol Use and Chronic Health Conditions Mini Video Series

Show Notes

Pearl 1: Naltrexone reduces the urge to keep drinking

How does naltrexone work?

  • Blocks opioid receptors from binding with alcohol-induced endogenous endorphins
  • Does NOT precipitate withdrawal
    • Even if the patients drink while taking it
  • Patients may describe:
    • Less craving
    • Less reward from alcohol
    • Having one or two drinks without the same urge to continue
    • Walking past a liquor store without thinking as much about drinking
  • Complete abstinence is not the only sign that it is working. 
    • Naltrexone reduces return to heavy drinking even when it does not eliminate ALL alcohol use
      • NNT of 11 to prevent heavy drinking
    • Naltrexone reduces craving intensity
      • Shifting the balance in favor of the patient’s motivation over their cravings

How to prescribe naltrexone?

  • First, confirm the patient is not taking the following:
    • Methadone
    • Buprenorphine
    • Prescribed/nonprescribed opioid analgesics
      • Naltrexone will precipitate acute withdrawal.
  • Anticipate upcoming opioid needs
    •  Ex. planned surgeries or potential acute injury pain management.
  • Oral naltrexone:
    • Start with 50 mg daily 
    • Increase to 100 mg if a partial response or minimal effect is observed without side effects  
  • Extended-release injectable naltrexone: 
    • 380 mg IM every four weeks
    • Individual variability can cause its effect to wear off early
    • To prevent this, daily oral naltrexone can be added starting on day 21
  • Adverse Effects: Nausea, headache, dizziness, and fatigue are common
    • Typically mild
      • Resolve after the first few days
    • Consider starting at 25 mg daily for several days if nausea is a concern

What if naltrexone “didn’t work”?

  • Reassess:
    • Was the patient taking it consistently?
    • Was the dose adequate?
    • Was the outcome defined only as complete abstinence?
    • Did cravings or drinking intensity improve even if drinking continued?
    • Did the timing match when cravings or drinking were most likely?
  • Naltrexone Dosing
    • Maximal efficacy can drop sooner than 24 hours
      • Due to individual variability, leading to breakthrough drinking
    • Taking the medication 1 hour before anticipated cravings or drinking windows increases efficacy!
    • For intense breakthrough cravings, consider
      • Splitting the daily dose into twice-daily administration OR
      • Double the total dose 
    • PRN dosing is effective for patients with intermittent binge-drinking patterns to target high-risk scenarios 

What about patients with liver disease?

  • Naltrexone is considered safe in cirrhosis and stable decompensated cirrhosis (expert opinion)
  • Avoid in 
    • Acute liver failure
    • Acute decompensated cirrhosis
    • Active GI bleed
    • HRS
    • Rising liver enzymes 
  • Naltrexone has dose-dependent toxicity
    • Much of the data comes from the earlier weight loss studies that had higher doses involved (150-300 mg). A, B 

Pearl 2: Remember acamprosate when opioids or liver disease take naltrexone off the table

When does acamprosate fit?

  • Acamprosate: FDA-approved for maintaining abstinence from alcohol
  • Consider it when:
    • Patient has already stopped drinking and wants to remain abstinent
    • Patient is taking opioids or may need them for acute pain
    • Significant liver disease
      • Makes naltrexone less desirable
    • Patient prefers a medication without opioid receptor blockade
  • Acamprosate is not hepatically metabolized and has evidence for reducing return to any drinking.

Acamprosate dosing?

  • Two ways:
    • 333 mg x 3 tabs = 999mg 2x/day
    • 333 mg x 2 tabs = 666mg 3x/day
  • Takes at least 4 weeks to have full effect
    • It can be taken for 48 weeks and then stopped; it will still have its effect for the next 12-48 weeks
  • The NNT is 12 to prevent return to drinking.

Any dose modifications needed for acamprosate?

  • Acamprosate is renally cleared!
    • Reduce the dose when creatinine clearance is 30–50 mL/min
  • Do NOT use when creatinine clearance is less than 30 mL/min

What are the acamprosate common, but rare adverse effects?

Pearl 3: Topiramate 

Topiramate use?

  • Off-label option for Alcohol Use Disorder
  • Reduces heavy-drinking days and percentage of drinking days
    • Performs at least as well as naltrexone
      • NNT ≈ 9–13 depending on the drinking outcome
    • At least as effectively as naltrexone
  • Who is the ideal patient for topiramate?
    • Ineffective, partial response, contraindication, or intolerance to FDA-approved AUD therapies (naltrexone, acamprosate)
    • Comorbidities 
    • Patients who would benefit from appetite suppression and weight loss 
      • Rather than harmful
    • Patients able to comply with outpatient titration and close monitoring 

Topiramate dosing?

  • Start low and titrate slowly to minimise adverse effects.
  • Outpatient Schedule:
    • 25 mg once daily or 25 mg twice daily (BID)
      •  Increase by 25–50 mg/day every week as tolerated.
    • Target Dose: 100 -150 mg BID (varies based on patient response).
    • Inpatient Considerations: 
      • Allows faster titration (every ~48 hours)
        • Caution: Rapid titration and higher starting doses = main drivers of cognitive dysfunction
      • Ensure the planned titration schedule is documented in the discharge summary with clear follow-up arranged. 

Topiramate precautions?

  • Adverse Effects & Safety Precautions:
    • Dose-Limiting side effects:
      • Cognitive slowing
      • Word-finding difficulty (important in patients requiring sustained mental concentration).
    • Other Side Effects: Paresthesias, fatigue, appetite suppression, and weight loss.
  • Renally excreted
    • 50% dose reduction is advised for CrCl <70 mL/min
  • Contraindications & Warnings:
    • Avoid in patients with a history of kidney stones
      • Topirmate has carbonic anhydrase-inhibitory activity causing 
        • Hypocitraturia,
        • high urine pH,
        • Hypercalciuria,
        • and favoring calcium-phosphate stone
    • Avoid in acute angle-closure glaucoma
    • Risk of metabolic acidosis. 

Pearl 4: Gabapentin, Disulfiram, and GLP-1

Gabapentin

  • Off-label use
    • Reduces heavy drinking
    • Eases anxiety during alcohol reduction
  • Best when drinking complicated by 
    • Anxiety
    • Insomnia
    • protracted withdrawal, or 
    • neuropathic pain (alcoholic/diabetic).
  • Used in outpatient alcohol withdrawal protocol 
  • Standard Target: 
    • 1,800 mg/day (typically 600 mg TID; can go up to 900 mg TID).
  • Alternative Taper: 
    • Front-loaded high dosing during acute withdrawal followed by a long-term taper.
  • Mandatory dose reductions for renal impairment.
  • Side Effects:
    • Sedation
    • Dizziness
    • Fall risk
    • Misuse/abuse risk in vulnerable patients 

Disulfiram

  • Disulfiram does NOT reduce craving 
    • Creates a physiologic deterrent
      • Causes an unpleasant and potentially dangerous reaction if alcohol is consumed
  • It is best understood as a behavioral intervention that “takes alcohol completely off the table”
  • Ideal Candidates:
    • Strict abstinence goal
      • NOT intended for harm reduction/controlled drinking
    • Highly motivated patients who understand and explicitly desire a deterrent
    • Patients with a reliable support system or responsible partner for observed dosing
      • Supervised adherence shows the strongest efficacy

GLP-1 receptor agonists

  • GLP-1 receptor agonists are promising but remain investigational for AUD
  • Clinical evidence is still limited 
    • Small samples
    • Short follow-up
    • Uncertainty about long-term AUD outcomes
  • Do NOT prescribe a GLP-1 receptor agonist solely for AUD outside an appropriate research or specialist context
  • If a patient already has an established indication, such as type 2 diabetes or obesity, a possible effect on alcohol use may be an additional consideration
    • Rather than the primary indication

Further Reading

Pearl 5: Do not confuse withdrawal management with AUD treatment

“Detox” treats withdrawal, not the underlying disorder

  • Alcohol withdrawal management may be lifesaving, but withdrawal management alone is not an effective treatment for AUD.
  • Think of withdrawal treatment like closing the anion gap in diabetic ketoacidosis!
    • Necessary for the acute crisis
    • Insufficient for long-term disease management
  • During hospitalization or detoxification:
    • Treat withdrawal adequately
    • Discuss the patient’s longer-term goals
    • Offer medication for AUD
    • Provide the discharge prescription
    • Arrange follow-up before discharge

Choose the withdrawal setting based on medical risk

  • Ambulatory or freestanding withdrawal programs may be highly protocolized and have limited medical staffing!
    • Hospital-level management may be safer for patients with:
      • Active hallucinations, delirium, or severe withdrawal
      • Prior withdrawal seizures or delirium tremens
      • Significant traumatic brain injury or seizure disorder
      • Unstable cardiovascular disease or risk of arrhythmia
      • Acute medical or psychiatric instability
      • Any active inpatient needs outside of withdrawals
      • Need for medications the facility cannot provide or monitor

If transferring a patient to a residential program, confirm that the patient will arrive with essential medications or can obtain them promptly.

“Rehab” is not automatically superior to outpatient care!

  • Residential treatment may be useful when:
    • Housing is unsafe or unstable
    • The patient’s home environment is saturated with alcohol or other substance use
    • A structured setting provides safety that cannot be recreated in outpatient
  • However, residential programs vary substantially in quality 
    • May not provide evidence-based medications or therapies
  • For many patients, intensive outpatient programs achieve outcomes comparable to inpatient or residential treatment
  • Before recommending residential treatment, ask:
    • Does the program offer medications for AUD?
    • Does it provide evidence-based behavioural treatment like CBT?
    • Can it manage the patient’s medical and psychiatric conditions?
    • What is the transition plan after discharge?
    • Will the patient be connected to ongoing outpatient care?

How long should medications be continued?

  • The optimal duration is NOT well established
  • Continue treatment while the medication is:
    • Helpful
    • Tolerated
    • Supporting the patient’s goals
  • Before stopping, consider whether the patient has:
    • Stable recovery
    • Reliable coping strategies
    • Improved housing and relationships
    • Treatment for co-occurring psychiatric or medical conditions
    • A plan for new cravings or a return to drinking
  • Set a high threshold for stopping a medication that has played a major role in recovery
  • If drinking returns, reassess and adjust the treatment plan rather than treating it as failure

Transcript

Dr. Sarah Wakeman: I think providers are sort of like, “Do you want to try naltrexone now? Okay, whatever.” Whereas with other medications, we sell it, right? Even though the number need to treat for other medications is way higher than the number needed to treat for naltrexone. We are all in on our GDMT for heart failure, and we’ll really share with the patient why we think it matters and why we think it’s going to help, even if the benefits are relatively marginal. And yet I feel like with alcohol use disorder medications, in part because I think sometimes we don’t know the evidence or we feel ambivalent ourselves, we don’t really sell it. So I try to go all in on the benefit of medications and also planting the seed that there’s lots of different options, and just because one isn’t helpful doesn’t mean that medications won’t help, that we can always trial other things in the same way we think about managing, again, hypertension or heart disease or some other illness.

Dr. Shreya Trivedi: Welcome to the Core IM Five Pearls podcast. I’m Dr. Shreya Trivedi, and I’m joined by

Dr. Ram Sundaresh: Hi, I’m Dr. Ram Sundaresh. I’m board-certified in addiction medicine, and I’m currently a GI hepatology fellow at the University of Michigan.

Dr. Shreya Trivedi: Yes. And this episode is made in partnership with the American College of Physicians and made possible by a grant from the American Society of Addiction Medicine.  And with that, let’s meet the discussants for the episode, two of whom were actually Ram’s preceptors back in addiction medicine fellowship.  First up is Dr. Michael Bierer.

Dr. Michael Bierer: I’m an internist and an addiction specialist, and I’ve been in Boston, linked to Mass General Hospital for about 40 years.

Dr. Alyssa Peterkin: My name is Alyssa Peterkin. I am an internist and addiction medicine doctor at Boston Medical Center.

Dr. Sarah Wakeman: I’m Dr. Sarah Wakeman.  I’m an addiction medicine specialist by way of internal medicine, and I’m a senior medical director for substance use disorder across our academic health system called Mass General Brigham.

Dr. Shreya Trivedi: All right, and this episode is going to be action-packed with tons of medication pearls, as well as management blind spots, for example, with detox. Let’s get started with a fan favorite, naltrexone.

#1: Naltrexone

Dr. Sarah Wakeman: My spiel about naltrexone for patients, the way that it works, and I will say this: it sticks with the opioid receptors in the brain, which at first feels kind of counterintuitive for alcohol use disorder. We use an opioid blocker for alcohol use disorder, but one of the ways that alcohol is reinforcing and causes pleasure is by activating the endogenous endorphin system. And so it’s actually the release of endorphins binding to the new opioid receptor. That’s one of the pathways that reinforces the pleasurable effects of alcohol. And so if you block that pathway, people don’t get sick if they drink, but what they describe is they don’t feel the urge to keep on drinking.

Dr. Ram Sundaresh: So it helps to set expectations. It’s not like you’re taking naltrexone and it’s this huge dramatic experience. It’s actually pretty subtle, and it works behind the scenes to really turn down the volume knob on cravings.

Dr. Shreya Trivedi: Ram, I honestly had not appreciated that aspect of naltrexone. I’ll often break up on rounds like, “Oh, the number needed to treat is 12 for reducing heavy drinking days”  I think I haven’t translated that subtlety about turning down the knob on cravings as well in my patient counseling.

Dr. Ram Sundaresh: I like to tell people we all have a mind-body connection, and that’s really what naltrexone works on. So if you’re walking past a liquor store, your body remembers what it felt like to reach for alcohol. But with naltrexone, you’ll notice that those feelings and cravings will be less intense.

Dr. Shreya Trivedi: Yeah, that is really helpful kind of imagery of what a patient can expect because I think for me, what I want to do next time I prescribe someone naltrexone is to paint for them, “Hey, a win for naltrexone doing its job is you having less intense cravings.”

Dr. Ram Sundaresh: Right. It’s a huge win. And oftentimes what patients on naltrexone will say is, “I had one or two drinks and I just didn’t have the same urge to keep drinking.”

Dr. Michael Bierer: A lot of times people say, “Oh, that drug didn’t work for me. Naltrexone didn’t work for me.” And it’s possible that the dose was too low or mistimed because IM naltrexone. People think that the IM naltrexone shot lasts 28 days, but it doesn’t. There are a lot of people who feel it wearing off after 20 days. So I typically will give a prescription for PO naltrexone with the instructions to take daily starting 20 days after any intramuscular naltrexone injection. And that sort of takes care of the follow-up problem if someone doesn’t quite get to a clinic for the next shot because it does wear off before 28 days.

Dr. Shreya Trivedi: Oh, okay. There were tons of good points in there. So one is that intramuscular IM naltrexone. It’s a monthly medication, queued 28 days, but for some patients it might wear off after 20 days and so may be good to send them with some oral naltrexone to the pharmacy to hold them over until their next intramuscular injection.

Dr. Michael Bierer: And the pill lasts, I think it’s eight hours. And so people are taking it once a day and still finding they’re drinking at night. And there’s individual variability, but sometimes you want to time it before your peak drinking occurs. So Ram has instructed patients to take it when they leave work rather than first thing in the morning.

Dr. Ram Sundaresh: Right, exactly. The pharmacinetics really varies for all of these. And for oral naltrexone, it takes about an hour to kick in after you take it. And then while yes, it’s technically a 24-hour duration of action in practice, it may last a bit shorter than that and the half-life is actually only four hours. So I find that playing around with the timing of the medication can really make a big difference.

Dr. Michael Bierer: I tend to like drugs first thing in the morning because I had a patient who told me about their buprenorphine, “I take it before my addiction wakes up. First thing, I take it when my eyes open.” So sometimes if that’s the case and people are drinking all day, you may want to split the dose of naltrexone or double the dose. And then there are other ways of fancy ways of using naltrexone, PRN or only when drinking, that sort of thing.

Dr. Shreya Trivedi: Wait a minute. We’ll get to timing in a second, but did he just say he could split up the dose or double the dose and maybe even give it PRN? I’m curious, have you done some naltrexone pharmacokinetics? For example, have you given it twice a day? Has it been  Effective?

Dr. Ram Sundaresh: Oh yeah, all the time. Yeah, super effective.

Dr. Shreya Trivedi: That’s good to know. I haven’t done that in my practice. I think the other thing he mentioned was giving naltrexone just PRN. I’m curious what type of patient might like, “Hey, just pill in the pocket naltrexone might be effective for.”

Dr. Ram Sundaresh: I’ve definitely used it. I think it really works best for the young 20-something year old who binge drinks at a party. And so there’s very intermittent heavy drinking, but in between not a lot of drinking. And so that’s the Sinclair method. You take a dose right before the event. Or for the person who wants to regulate their drinking, but instead of taking maybe eight drinks, they’ll have two drinks, and they’re satisfied without really experiencing that loss of control. And everyone is a little bit different. So I’ve had some people with intramuscular naltrexone once a month, and then I give a little bit of as-needed oral naltrexone on top of that.

Dr. Shreya Trivedi: There are so many different ways to think about it and what might be right for your patient. I think the other thing in terms of just trying to be better about patient counseling also is how long do you tell them to wait before they say, “Eh, naltrexone’s not working?”

Dr. Ram Sundaresh: Yeah. Most people should feel something within the first week or so, but I like to give it a good month of taking it consistently and really try to clarify how did their cravings, their number of drinks, their sense of control, how did all of that change over the course of that month? And of course, definitely make sure they’re on a good dosage before writing it off. At minimum 50 milligrams of naltrexone, but there’s definitely room to bump it up to a hundred milligrams or even more than that.

Dr. Sarah Wakeman: With oral naltrexone, I think that the standard dose is 50 milligrams, but you can definitely go higher than that. And many studies have looked at a hundred milligrams daily or even higher. Although we tend to use 50, it doesn’t have to be the only dose that you use.

Dr. Shreya Trivedi: Fair. So I guess who are the people that you might bump up to a hundred milligrams of oral naltrexone?

Dr. Ram Sundaresh: Either someone who’s noticed a difference but it’s not quite strong enough or they haven’t really felt an effect, but they’re also not having too many side effects that are bothersome.

Dr. Shreya Trivedi: Okay. Speaking of side effects, what are the side effects to know about when it comes to naltrexone?

Dr. Sarah Wakeman: The other really important thing to remember is that the worries about impact on hepatotoxicity are totally overblown with naltrexone, that we’ve used safely in patients with cirrhosis, and that the health harms of ongoing alcohol use are far more significant than any worry about hepatotoxicity from naltrexone.

Dr. Ram Sundaresh: So naltrexone is safe in cirrhosis, and I’m okay even starting it in stably decompensated patients with cirrhosis. The only time I really hold off is an acute liver failure, severe hepatitis, actively uptrending liver enzymes, or acutely decompensated cirrhosis with SVP, HRS, or an acute GI bleed. Wait for those issues to stabilize more so it doesn’t cloud the picture and people don’t start to blame the naltrexone.

Dr. Shreya Trivedi: Yeah. I feel like people can easily blame the naltrexone. I feel like it happens all the time. You’re scratching your heads like, “Oh, why did those AST and ALT bump and naltrexone gets discontinued?”

Dr. Ram Sundaresh: Exactly. And percent of the time the answer is just keep the naltrexone going. So keep in mind it’s really a dose-dependent hepatotoxicity. Really, it starts to become more relevant when we’re getting to naltrexone 150 milligrams or 200 milligrams or more than that. The hepatotoxicity data really came from these early weight loss studies, and they were looking at 300 plus milligrams. And so if you’re really worried, you can check liver enzymes, but just do it in a way that doesn’t scare the patient.

Dr. Shreya Trivedi: Yes, yes. All good points. So basically, the takeaway is you are not checking LFTs for a patient who’s just on the run-of-the-mill naltrexone 50 milligrams.

Dr. Ram Sundaresh: Yeah, definitely would not check at 50 milligrams.

Dr. Shreya Trivedi: Great. And then what are the side effects to know about when it comes to naltrexone?

Dr. Ram Sundaresh: Some people get a little nausea, mild headaches, and oftentimes it kind of goes away on its own in a few days.

Dr. Shreya Trivedi: Okay. And then in terms of contraindications, anything that makes naltrexone off the table for someone?

Dr. Ram Sundaresh: So it’s contraindicated with long-term opioids. And so if you do have someone that has regular opioids and then they start to take naltrexone, it basically pushes them into precipitated withdrawals, and it just goes back to how naltrexone works.

Dr. Shreya Trivedi: So let’s pause here and summarize naltrexone. I think what I’m taking away is to move away from my initial reflex of naltrexone oral 50 milligrams for everyone. I think especially in terms of navigating some of the “Oh, it didn’t work for me.” Some people might need it twice a day. Some people might need the timing to be better right before they might leave work, for example. Some people might want intramuscular naltrexone, but need some oral naltrexone as needed to bridge them to their next injections or if cravings get really bad. And then Ram, I think it was also helpful to appreciate the phenotype of people who might be okay with naltrexone as a pill in the pocket, just PO, PRN as needed before social events when they’re around alcohol.

Dr. Ram Sundaresh: Exactly. The bottom line is that naltrexone has so many different ways that you can use it. It’s a very adaptable medication, and so the better you can understand what’s someone’s context, how does drinking fit into their life, that’s really where you can tailor these approaches for exactly the patient that you’re dealing with.

Dr. Shreya Trivedi: Okay, great. And then I think the other thing I’m changing in my counseling things to you again is that I think, yes, I always mention, “Hey, there’s really good data for naltrexone, but I never specify the intent here is to turn down the knob on cravings.” I think my worry is that when someone hears how effective it is, if they feel like they don’t have complete abstinence, that naltrexone’s not working, but nope, the win here is we’re going to decrease the intensity on the craving and hopefully have you have a decreased number of drinks that you’re having.

Dr. Ram Sundaresh: Exactly. And everyone has their own internal motivator to cut down on drinking, and so it’s a constant battle between motivation and craving. And so naltrexone really tips those scales. When you’re turning down that volume up on cravings, you allow those intrinsic motivators to take predominance and help empower someone’s recovery. And absolutely, you can get folks that achieve complete abstinence with naltrexone.

Dr. Shreya Trivedi: Yes, that’s always a happy story

#2: Acamprosate

Dr. Shreya Trivedi: All right, Ram, I feel like I’d enter a confessional booth here because even as we were working on this episode, I recently had a patient who unfortunately had a really bad fallout with a business partner, invested a lot of money, and unfortunately was using drinking to cope. And unfortunately, in one of her binge episodes, she had a really bad fall and bleeding in various places, rib fractures, and with the fractures really needed opioids to help with that. She was interested in naltrexone, but unfortunately I couldn’t get it. As we just mentioned, she needed to be really weaned off the opioids for her to be able to take naltrexone. And my goodness, I so wish I had thought about acamprosate, but I didn’t.

Dr. Ram Sundaresh: Yeah. I mean, it’s such a great medication and the data’s really good. Sometimes it gets a bad rep, or it’s just not used as often, but there’s actually really good news.

Dr. Michael Bierer: Acamprosate is a very hard drug to take because most people prescribe a TID. You can prescribe it BID, and the pharmacokinetics are fine. A BID drug is, I think, doable. Some people can do TID, but acamprosate can be prescribed as three pills BID, and it’s effective, and it works.

Dr. Ram Sundaresh: Yeah. I mean, Acamprosate’s actually a really great medication. The data’s really good and it works really well. Sometimes it just gets a bit of a bad rep.

Dr. Shreya Trivedi: Yeah, maybe it was like the TID aspect of it that made me shy away.

Dr. Ram Sundaresh: Yeah, sometimes that can be a barrier, but the flip side is that some people actually prefer the TID dosing of Acamprosate, and it can really be a steady reminder, even an affirmation of the recovery goals in multiple time points throughout the day.

Dr. Shreya Trivedi: Yeah. Wait, I think I had just heard him say three pills. TID or BID? Curious why three pills?

Dr. Ram Sundaresh: Yeah, I mean, for some reason it only comes in the 333 milligram tablets, and so you either have to do three pills to get to the 999 twice a day, or you do two pills to get to the 666 milligrams TID.

Dr. Michael Bierer: I don’t know why, but take it for 48 weeks, and you can stop, and it still has an effect for the next 48 weeks. Why? Who knows?

Dr. Shreya Trivedi: Okay. So some really great pharmacokinetics here: if you do take Acamprosate, it has long-lasting effects after a year.

Dr. Ram Sundaresh: Yeah. Acamprosate’s fascinating, and I don’t know if it’s a pharmacokinetic thing. Maybe it might be more of a rewiring thing from its impacts on NMDA receptors, but we’re not really sure.

Dr. Shreya Trivedi: Yeah, I think whatever it is, we will take it. And you mentioned the data is really good. Can you talk a little bit more about that? What’s the number needed to treat?

Dr. Ram Sundaresh: Yeah, so with Acamprosate, they actually studied people who are abstinent from alcohol, and then they measured return to heavy drinking, and the number needed to treat is great. It’s around 12 to prevent return to any drinking. So there is pretty good data for maintaining abstinence.

Dr. Shreya Trivedi: And then how long do you tell patients to take acamprosate for it to have an effect, or before they throw in the towel to say, “Hey, Acamprosate’s not working for me?”

Dr. Ram Sundaresh: Similar to naltrexone, give it at least a month or so. And of course, the longer you stick with it, the more you’ll benefit.

Dr. Shreya Trivedi: And then what are the side effects of acamprosate we should look out for?

Dr. Ram Sundaresh: Mild nausea; sometimes people can get looser stools, but that also gets better with time. To be honest, I’ve never really had anyone with bothersome GI symptoms, but it is written on the label. And then of course we do have to renally dose Acamprosate, so especially if it’s creatinine clearance less than 30, it’s unfortunately going to be off the table.

Dr. Shreya Trivedi: Okay. All good things to know. Maybe if I’m summarizing what I’m taking away with regards to Acamprosate, it’s like, dear Shreya, remember to use it more often. There is good data, and I think thankfully, now I know I can actually prescribe Acamprosate twice a day and maybe get rid of some of the bad rep that it’s a TID medication. But I think as Rom, as you said, you’ve had some patients say that they actually like that it’s a TID medication and it’s a reminder to their commitment to alcohol abstinence. And then second thing is to really, I think, internalize for me that’s really effective in terms of helping people maintain abstinence. And even if they take acamprosate, I guess twice a day or three times a day for a little under a year, that they actually could have a durable effect even if they stop acamprosate.

#3: Topiramate

Dr. Shreya Trivedi: All right, let’s see what else we have in our wheelhouse. We’ve covered naltrexone. We covered acamprosate. Let’s get into topiramate.

Dr. Sarah Wakeman: My next go-to is topiramate, which is off-label and not FDA approved, but probably as effective, if not more effective than naltrexone. And topiramate patients all share this too. It’s been around for forever. We use it for lots of other things like epilepsy and migraines. It can cause loss of appetite and weight loss, which for some patients is a plus if they’re also worried about their weight or trying to lose weight. And the main challenge is just that you have to start low and titrate slowly, and so it does require ongoing follow-up. And sometimes I think we forget to do the titration. So if someone’s in the hospital for a week, they’re generally not going to get to a very high dose, maybe only the 25 milligrams or 25 milligrams twice a day. And the target dose is really a hundred milligrams BID or even 150 milligrams BID, and we would increase weekly by around 25 to 50 milligrams a week, depending on if a patient’s having side effects. The main side effects we worry about are cognitive slowing, so that’s really the dose-limiting side effect and why we start so low and titrate slowly, but also very safe and again, really effective.

Dr. Ram Sundaresh: Yeah. And in the inpatient setting, you can dose escalate a little bit more frequently, every 48 hours, every 72 hours. And then in the discharge summary, you can even write in the timeline for when to keep going up on the dose and by how much, and obviously stop whenever the side effects are getting too much to tolerate. And maybe you’re feeling some paresthesia, some lip tingling, even some brain fog. But if you’re still feeling the benefit, as long as you’re tolerating the side effects, that’s probably a good spot to hold off on going up further. And keep in mind, topiramate is a less subtle medication compared to naltrexone. There’s a much more noticeable visceral sensation in the body earlier on.

Dr. Shreya Trivedi: Maybe it works sooner than the taking into effect a week. Is that what you’re saying?

Dr. Ram Sundaresh: More so that you notice the effects sooner. So for someone that wants to know, “Hey, this is what I’m feeling when I take this,” the psychology of that might fit into someone’s recovery differently.

Dr. Shreya Trivedi: Oh, interesting. And then how good of a medication is topiramate?

Dr. Ram Sundaresh: Oh, it’s great. The number needed to treat is around seven to reduce heavy drinking days, maybe even stronger than naltrexone according to some of those studies. So the main trade-off is really the cognitive side effect. So if someone’s working a very cognitively heavy job, an engineer or a programmer, that’s something that would give me a little bit of a pause and consider an alternate agent.

Dr. Shreya Trivedi: Okay, so then who would you then think, okay, topiramate might be a good drug for?

Dr. Ram Sundaresh: I’ll think about topiramate for someone who’s maybe tried some of the FDA-approved options like naltrexone or acamprosate, but maybe didn’t have too strong of an effect from it. It’s a great next step, especially if they’ve got migraines, which it’ll co-treat. It can be a bit of a mood stabilizer as well.

Dr. Alyssa Peterkin: I also bundle that, right? It’s an off-label treatment for people who have cocaine use disorder. So is there another condition that I can address with this off-label medication?

Dr. Ram Sundaresh: And that’s a huge one because alcohol and cocaine are really frequently co-occurring, especially in the Northeast, and topiramate is perfect for those patients.

Dr. Shreya Trivedi: Yeah, I didn’t know. I definitely want to try to think about topiramate more. Next time I see a Utox positive for cocaine, and they’re coming in with withdrawals, definitely going to try to reach for some topiramate. There’s definitely some people I can think about right now who could use some topiramate. It’s good to know. Anything else we should know about topiramate, Ram?

Dr. Ram Sundaresh: We should avoid topiramate in someone who’s had previous kidney stones. And the other thing is that there is a bit of a stigma sometimes around topiramate. The brand name is Topamax, but some patients might refer to it as Dopamax because they feel really slowed down or dopey. Again, not everyone will get that way, and the goal is to get you to a good dose where you feel the benefits without feeling the cognitive side effects. And so I really try to just get a sense of what someone’s heard about topiramate in the past, because really the data is so strong.

Dr. Shreya Trivedi: Yeah, that’s awesome. Maybe this is a good place to pause and recap. So topiramate, it’s one of these medications that needs careful dose escalation with close monitoring. Ram, as you just said, it’s a medication where you want to get to a good dose without having some of the less desirable side effects like cognitive dulling. And then the doses that have shown to be effective is kind of 100 milligrams twice a day or 150 milligrams twice a day, which I think is helpful context because I’m sure the next time I look at someone’s med rec and I see they’re just sitting at topiramate 25 milligrams, I’ll be like, “Oh, maybe that’s not enough to help with the alcohol cravings.” I think the other teaching point for me is that I used to think that naltrexone was the one to rule them all. It was the most effective. But it sounds like if I’m thinking about all the meds that we’ve talked about so far, what I’ve learned is that acamprosate may be just as effective as naltrexone, and topiramate might have even stronger data. I say this with a grain of salt because these haven’t been studied head-to-head, but just good to know that there is good data that these other medicines can be effective too.

Dr. Ram Sundaresh: Right. All three of these are really great options, and really the flip side is that naltrexone is so much easier, so you don’t have to worry about dose escalation or monitoring for side effects in the same way. It’s a lot easier to prescribe, a lot easier to keep up with, and it still has great efficacy.

#4: Other meds

Dr. Shreya Trivedi: All right, let’s get into the other medications, right? Say for whatever reason we can’t reach for Naltrexone or Acamprosate or Topiramate, what are some of the other options that we might be able to reach for?

Dr. Michael Bierer: I think the other thing about alcohol use disorder is that comorbid psychiatric complaints or diagnoses are common and can be treated even in the face of drinking. So the use of gabapentin might be in a situation where anxiety is one of the things driving drinking. And so the problem is with that drug is that people don’t stop taking it, like a lot of things. We start them, and then they take on a life of their own. It’s not a problematic drug by and large.

Dr. Ram Sundaresh: So I really like gabapentin, where anxiety or even insomnia is a huge trigger for drinking, and the data shows that 600 milligrams TID is a good target dose to reach a decent reduction in heavy drinking, but you can go up even higher on the QHS dose, even 900 milligrams or even more, but definitely take caution, especially for anyone older or frail; would definitely consider dose reducing to 100 or 300 milligrams or even just hold off altogether.

Dr. Shreya Trivedi: Yeah. Okay, so it’s good to know we need to get to a high enough dose, like 600 to 900 to have an effect when it comes to anxiety.

Dr. Ram Sundaresh: Right. Usually when it’s 600 to 900 milligrams, they start to feel an effect, but keep in mind, when you’ve had a massive reduction in drinking, say from one pint of liquor a day down to a half pint of liquor a day, you’re going to feel some rebound anxiety. Gabapentin can really take the edge off of that and even help reframe that association that alcohol is what I reach for when I feel anxious. I feel like the other person to think about for gabapentin is someone that has really bad alcohol related neuropathy or diabetic neuropathy, and sometimes that pain can be so painful that that can be a huge trigger for drinking. Oftentimes when they show up with acute Alc Hep or they’re really sick, they may have a lot of other symptoms that are really taking the forefront of their medical care. They have nausea, fatigue, jaundice- all that’s taking the forefront. But then after three to six months, when that’s all cooled off, people realize they have this severe burning leg pain that’s not going away, and that can actually end up triggering people to go back to drinking. So gabapentin is great for that overlap.

Dr. Shreya Trivedi: That’s all helpful. I’m curious, Ram, have you ever had any hesitation from patients or other teams pushing back being like, “Well, aren’t we just replacing alcohol with something else that’s working on the GABA receptors, especially if it’s such high dose?” Can you feel guilty when I’m the one putting someone on 900 milligrams TID of Gabapentin? What can I say to that?

Dr. Ram Sundaresh: Yeah, I mean, it definitely comes up. I think that there’s really two things to think about. One is that we always have to make sure on a case-by-case level that the benefits are going to outweigh the risks. If severe anxiety is a major return to drinking or if 

Dr. Shreya Trivedi: Or sleeping. I had a patient recently where they were using alcohol to help them sleep, and I thought about, should I give them 900 at nighttime? But I’m like, “Am I just doing the same thing as alcohol does?”

Dr. Ram Sundaresh: Yeah, I mean, it’s all risk-benefit. So if someone is going to drink one to two pints of alcohol to help them get to sleep and they’re going to lose control and have all these other impacts, Alc Hep and withdrawals- gabapentin won’t have those same side effects. I mean, yes, it can be sedating, but it’s not going to cause Alc Hep. It’s not going to lead to withdrawals quite in the same way that severe acute alcohol withdrawals can manifest. Again, it’s always a conversation, case by case. I mean, the flip side is also for conditions like diabetes, and I love the diabetes analogy: if someone needs insulin and you’re prescribing them insulin, we don’t tell them, “Oh, now you’re just becoming dependent on a medication.” It’s important to maintain your glycemic control and avoid bad outcomes like DKA. So there is good data for it, and if you’re seeing someone that has erratic use of other sedating medications or they’ve struggled with benzos in the past, it definitely is appropriate to ask if this is the right medication for someone. And so one of the nice things about gabapentin is that there are even these outpatient alcohol withdrawal protocols based on gabapentin. And so you can use gabapentin to help taper someone off of moderate to heavy drinking where they may have some very mild alcohol withdrawal symptoms. And so even starting up front with the higher doses and gradually tapering it off over weeks to months can actually have a huge benefit.

Dr. Shreya Trivedi: Amazing. Lots of good stuff. I think the other medication to talk about is disulfiram. We had briefly mentioned it. It’s one that a lot of patients know about, but what else do you think we as clinicians should know about?

Dr. Ram Sundaresh: The best description I’ve heard of disulfiram is that it’s really a behavioral intervention where they go into it knowing that here’s the deal: it’s going to take alcohol off the table. And psychologically, I know that it’s not an option, and it has to be someone that engages with that motivator.

Dr. Michael Bierer: One way to use it safely is to have a responsible other who’s part of the dyad of recovery, and it doesn’t have to be a punitive jailer saying, “Take this pill.” It’s more like, “Darling, thank you for letting me be part of your recovery. I’m so happy to watch you take your disulfiram,” that sort of thing.

Dr. Shreya Trivedi: Okay. So are there people that you’ve actually seen want disulfiram, or you started disulfiram on and it made a difference?

Dr. Ram Sundaresh: Yeah, definitely. It’s a very carefully affected patient population, and it’s usually someone that has insight into their motivators, and they’re responsible enough to take it on a regular basis. And so oftentimes it’s someone who’s older, or they’re more familiar with it because disulfiram has been around for a lot longer, and they know they’re going to get violently sick. And so any drop of alcohol is just off the table. And so disulfiram is actually something we should avoid with liver disease. Unlike naltrexone, where it’s a dose-dependent hepatotoxicity, disulfiram is actually more idiosyncratic. And so if they have underlying liver disease, we just can’t predict at what dose it might develop some hepatotoxicity.

Dr. Shreya Trivedi: That sucks. I think just not knowing if this person will get hepatotoxicity from disulfiram.

Dr. Ram Sundaresh: Right. But aside from that, it’s important to counsel that they should avoid alcohol-based mouthwashes and aftershave and hand sanitizer just to make sure that they’re not going to get a mild reaction that could be pretty uncomfortable.

Dr. Shreya Trivedi: That is a great pro-tip in terms of counseling. And then I think last but not least, in terms of the other medications, is a new kid on the block: the GLP-1 meds.

Dr. Sarah Wakeman: The kind of new kid on the block, which is really exciting, is the whole class of GLP-1 medications, especially semaglutide, where I hope we may see FDA approval at some point in the not too distant future, but where we have great preclinical evidence and now a big clinical trial showing improvement in alcohol outcomes and seems to be a pan addiction, pan craving, obesity, obviously wonder drug that we are talking about in lots of different spaces, but on the addiction side seems to work across substances and in a randomized controlled trial amongst folks with alcohol use disorder weren’t seeking treatment showed significant improvement in alcohol use outcomes. So really exciting to think of that as an option.

Dr. Ram Sundaresh: So right now we have really good phase two data. It’s very promising, preclinical outcomes, and they’re looking at reduction of volume of drinking. We don’t yet have the robust clinical outcomes, but the phase three studies are right around the corner. And the thing that’s really exciting about GLP-1 agonists is that they’re also really helpful for steatosis and liver disease. So if you can find an insurance indication if they got diabetes or obesity, it can actually help with their liver disease as well.

Dr. Shreya Trivedi: Great, Ram. Why don’t we summarize all good things when it comes to gabapentin, disulfiram, and GLP-1s? How do you think about them, and how do you think people should approach when they should reach for one versus the other?

Dr. Ram Sundaresh: Yeah, these are great off-label options that are really good for certain niche populations. And so gabapentin, disulfiram, very carefully selected. Gabapentin is really great for those folks where anxiety is a huge trigger for return to drinking, or even neuropathic pain in folks that have alcohol- or diabetes-related neuropathy. Insomnia, where that’s a huge trigger. Gabapentin is something to think about. Disulfiram is for the very carefully selected patient who is specifically interested in that motivator of taking alcohol off the table. The GLP-1s are super promising. The coverage from an insurance standpoint is really going to be for those folks who have obesity to have diabetes. If they have concurrent alcohol use disorder, it’s great. And it also has the added perk of helping with steatosis, so it can even help their liver disease too. But the phase three studies are right around the corner, and hopefully soon enough, we’ll get an on-label indication for it.

#5: Detox and rehab blind spots

Dr. Sarah Wakeman: I think the most common thing that often people think of is the best treatment for alcohol use disorder for addiction treatment generally is detox and rehab, and that is definitely not true, so it’s good to challenge that misconception. “Detox” is really inpatient medically managed withdrawal, and for alcohol use disorder, that often is needed as a first step. But if all someone does is go to detox, the risk of recurrent This is incredibly high. And so again, really thinking of a chronic care management model, if you think of detox as almost like closing someone’s gap when they have DKA, yes, that’s necessary, but it’s not sufficient to manage diabetes. You need to both manage that acute crisis, and then you need to treat the underlying condition.

Dr. Shreya Trivedi: That’s a helpful context in terms of thinking about detox. But I’m assuming when our patients, when they get discharged from the ED and go to detox, that then these patients are going to get put on naltrexone or acamprosate or whatever medication that makes sense for them when their withdrawal’s over.

Dr. Ram Sundaresh: I mean, in my experience, it’s hit or miss, and more often than not, they end up not starting pharmacotherapy for alcohol use disorder.

Dr. Shreya Trivedi: Oh, all right. That sounds good to know. Maybe next time I discharge someone to detox to maybe also make sure they have an addiction medicine appointment or maybe their PCP knows to help think about medication management and other supports. And then I guess in addition to that, it would be good to know who are the right people to send to detox?

Dr. Alyssa Peterkin: For me, the biggest thing of when I was a fellow, I spent some time in what’s commonly known as detoxes. We’re trying to move away from that word, though. We call it ATS, or Acute Treatment Services. And I was amazed at what was happening, what could be done, but I think there was someone who came in the night before and he was actively having hallucinations and I was like, “Oh my gosh.” And then my attending was like, “Yeah, he has to go back to the hospital. We can’t handle that.” It’s very protocolized. So it’s like you’re here for alcohol withdrawal. They tick the box. Okay, we do diazepam here. They tick that box, and it gets started. So when the nurse has so many patients to manage, you have to have someone who’s kind of ticking those boxes. It’s fairly easy to manage. Sending people there who have maybe a major traumatic brain injury, a seizure disorder, not the ideal candidates or have a complex risk for heart failure might not be where you want to send them. And the other thing is that they have to have meds with them. If they’re coming in in the evening, some of these places are not affiliated with pharmacies. They have to order out medication. So if they’re meds that you think your patient is going to need within the next 24 hours, you make sure they come with their supply or at least send refills to the pharmacy so they can pick them up before they go to these programs.

Dr. Ram Sundaresh: Right. So the teaching here is that these detox centers, they can often be very nursing-driven. It’s very protocolized. So anyone with complex withdrawals, have had seizures or DTs before, or if they’re at risk of going into AFib with RVR, these are not going to be well suited for going to a detox center. And so keep in mind, these are not hospitals. They can’t do daily labs. They don’t have telemetry monitoring. Really, it’s for garden-variety, bread-and-butter, uncomplicated alcohol withdrawals that you can manage with a very protocolized approach.

Dr. Shreya Trivedi: That again is helpful context. I guess in terms of other dispo or destinations in addition to detox, we’re sometimes discharging people to these rehabs or residential rehab, as you’ve called it before. And curious if we can think about what exactly that is in some of the blind spots there.

Dr. Sarah Wakeman: Rehab is this idea of sending people away to a residential setting where they’re removed from their environment and have intensive treatments.

Dr. Shreya Trivedi: So how long are these rehab or residential treatment programs stints for?

Dr. Ram Sundaresh: It ranges. Some of them are around two to three weeks. Some of them are a few months. It varies based on the state and the context. There are some that are more transitional and longer term, but they all have a varying combination of individual therapy, group sessions, recovery activities, counseling, and you really have a little mini community that’s working on recovery with you.

Dr. Shreya Trivedi: That’s great.

Dr. Sarah Wakeman: On the one hand, there can be benefits of that, especially if someone doesn’t have housing and the alternative is going back to the street and being in chaos, being in a structured setting can be really helpful. On the other hand, there’s not great evidence for residential treatment programs. There’s a lot of heterogeneity in what’s offered there, and sometimes the quality isn’t all that great.

Dr. Ram Sundaresh: So it is true that some alcohol rehabs or residential programs are not very good and they don’t necessarily do evidence-based practices and they charge a huge premium, but there definitely are places that are really good too.

Dr. Shreya Trivedi: And Ram, in your experience, what’s the best example of a residential rehab versus the one that was the most not evidence-based?

Dr. Ram Sundaresh: The good ones are going to use proven therapies, things like CBT, good therapy modalities. They’re working on your triggers. They’re working on relapse prevention planning. They’re trying to help build coping strategies. How do you deal with these difficult feelings that come up and can trigger alcohol use? On the flip side, I’ve seen some that use equine therapy. You ride a horse and

Dr. Shreya Trivedi: Oh my gosh.

Dr. Ram Sundaresh: Or surf therapy. There’s an area in LA; they call it the Rehab Riviera, and they charge tens of thousands of dollars a month and these huge premiums, and executive rehab is the term they use, but yeah, it’s a whole industry sometimes. But again, there really are places that are doing a great job, and they’re really trying to focus on

Dr. Shreya Trivedi: This. And how would one know? I’m assuming the Google reviews are obviously taken with a grain of salt based on that person’s experience, but is there any objective way you know, hey, this rehab would be good for you versus is it just kind of word of mouth?

Dr. Ram Sundaresh: Yeah, it’s a lot of word of mouth, and I think this would be a great opportunity to reach out to your friendly neighborhood addiction medicine specialist who really knows what’s going on locally and what are the good places to send people.

Dr. Sarah Wakeman: Not all residential programs offer medications or offer actually evidence-based therapies. So ambulatory treatment very much is as good if not better, in terms of long-term outcomes. And so that can be medical management with a doctor, where the doctor is prescribing medication and doing medical counseling, plus often therapy or sort of therapy-based interventions like cognitive behavioral therapy. And that can occur in an intensive setting, which we talk about as IOP, which is usually three days a week of intensive groups and individual counseling or a PHP is even more intensive, usually two weeks all day, but you live at home.

Dr. Shreya Trivedi: That’s so interesting that the data actually shows that seeing an addiction medicine person outpatient may be better in terms of outcomes than a rehab. And that’s, again, really helpful context in terms of thinking about disposition options. But I guess with everything, data is data, and the individual patient in front of you is different, but helpful in terms of thinking about maybe they have a better residential rehab, but to think like, “Hey, could seeing someone outpatient be helpful versus would that residential rehab be the best place for this person?”

Dr. Ram Sundaresh: Yeah. And really the phenotype of someone who benefits from residential rehab. It’s someone who has a chaotic life situation, and maybe they’re unsheltered or their social environment is full of people who are actively drinking or using substances, and that would otherwise be a major trigger to be around.

Dr. Shreya Trivedi: Yes, definitely. Ram, could you do us the honor of maybe summarizing for us some of the key blind spots or what you want people to take away when it comes to discharging people to detoxes and to residential rehabs and what we can do better?

Dr. Ram Sundaresh: Right. So detox, residential rehabs, these are not hospitals. They can’t do daily blood draws. They don’t have close telemetry monitoring. It’s very protocol nursing driven. And so, garden-variety bread-and-butter alcohol withdrawals where they don’t have anything else that would otherwise keep them in a hospital. That’s the perfect person to send to a detox center. And remember, this is short-term treatment. It’s like closing the gap for your DKA, but it’s not long-term, and it’s not going to change the trajectory of someone’s recovery if you’re not also pairing it up with longer-term treatments like pharmacotherapy, counseling, and really understanding what’s driving someone’s alcohol use. Residential rehab programs are great, but the data is really mixed, and they’re very hit or miss. There’s some that are evidence-based and there’s some that aren’t. And so really it’s a matter of identifying what are the patient’s needs and if they have a very chaotic life environment, if they need a clean slate to work on their recovery, this is a great place to do that.

Dr. Shreya Trivedi: That is a wrap for today’s episode. If you found this episode helpful, our ask is to please share it with one other person that could use this, and I think it’ll be so impactful. I know for me, I’ve changed the way I’ve gone in and talked to patients, and it’s really kind of undoing some of these misconceptions or traps that we can all fall into.

Dr. Ram Sundaresh: And thank you to our reviewers and to Dr. Jesse Powell for the accompanying graphic.

Dr. Shreya Trivedi: And if you want to check out more that ACP has done on the topic, particularly these really great videos on motivational interviewing, I believe Dr. Peterkin was involved with some of them. We’ll put the link in our show notes. As always, opinions expressed are our own and do not represent the opinions of any affiliate institutions. Thank you and take care.

References