Kendal Williams, MD (Host): Welcome everyone to the Penn Primary Care podcast. I'm your host, Dr. Kendal Williams. So when I started this podcast, I had this image of basically inviting grand round speakers onto my podcast. And we would talk about what they talked about so that you would hear the, all the interesting and varied grand rounds that occur at Penn, in podcast form, and they could spread out to the greater community, those who couldn't actually attend it in person.

That actually didn't really work out, as a way of getting guests. But in this case it has. Some of my colleagues here at Penn in the division of General Internal Medicine put together a fabulous grand rounds that updated various aspects of addiction medicine, spanning from tobacco and alcohol all the way to fentanyl.

And there were so many really great pearls in there that I asked them to come on the podcast and sort of unearth those pearls for a greater audience. So joining me today are three of my colleagues from the division of General Internal Medicine. Dr. Rachael Truchil is Associate Professor of Medicine at Penn.

She is the Medical Director of the Penn Refugee Clinic. She is also a faculty in addiction medicine and the leader of addiction medicine within the division of General Internal Medicine. I truncated, Rachael's, bio, uh, and description because she does a lot of other stuff. But, Rachael, thanks for coming on.

Rachael Truchil, MD, MPH: Yeah, you got it. Great to be here.

Host: Thank you. And again, we have Dr. Maggie Lowenstein back on the podcast. Maggie was here earlier talking about the management of opioid abuse in the primary care setting. She is an Assistant Professor of Medicine at Penn. She is an addiction med researcher, is on the Penn Med Opiate Task Force, and attends on the Addiction Medicine Services at Penn.

Maggie, thanks for coming.

Margaret Lowenstein, MD, MPhil, MSHP: Thanks for having me back.

Host: And new to the podcast is Dr. Ashish Thakrar, who is, also an addiction medicine researcher here at Penn, Assistant Professor. He's an internist and expert in this field. And, Ashish, thanks so much for coming on.

Ashish P. Thakrar, MD, MS: It's my pleasure. Thanks for having us.

Host: So, we're actually just going to kind of go through their grand rounds in sort of podcast interview formats and talk about the topics that they address in their grand rounds. And we're going to focus on three areas, tobacco, alcohol, and then also talk about the fentanyl epidemic, which is really still inundating our hospitals.

So, let's start where you started your grand rounds. Rachael, you described a 47-year-old man, a contractor with hypertension, smokes a pack a day for the last 30 years, just comes in for an annual visit, doesn't really want to quit smoking, does have a lot of psychosocial stressors, and doesn't really want a medication.

And so you outline some of the options that we have for this patient. What's the first thing you turn to?

Rachael Truchil, MD, MPH: Yeah, so I think, the important thing is really that even if patients come in and they are not super motivated to quit, not interested in complete cessation of tobacco, that there's a lot of benefit to having a discussion about medication for tobacco use disorder. Because it can really help patients cut down and actually get to abstinence, even if that isn't necessarily their goal.

I mean, maybe it's not the best time, maybe, they have other things going on, but having the conversation and saying, Hey, this is something that it seems like you're struggling with, and even though now might not be their best time to quit completely, let's start this medication so that it will make it easier when you do get there.

And really first line is, varenicline or, Chantix. And if you start it in somebody who is not ready to quit, it actually is associated with better outcomes. So, improved rates of total cessation anyway. And so I think this is a pearl in that you really can start using varenicline even when patients are not ready themselves at that moment to quit.

Host: And so varenicline is considered the single most effective option to help people stop smoking. Right?

Rachael Truchil, MD, MPH: Absolutely. It's number one on the list and should be offered as first line.

Host: And is effective as you note even in patients who really come in and are not feeling ready to quit, but are at least open to the possibility of starting it, right?

Rachael Truchil, MD, MPH: Right. So I think a lot of patients know that they should quit and want to ultimately quit, but maybe it's just not the right time, and this is a great, great opportunity to start something like varenicline.

Host: Do we know how it helps people in this way, how it helps them get more motivated? Is it, you know, I think of Wellbutrin, it has some antidepressant effects, which can give you some mental energy to tackle a new task like quitting smoking. Does varenicline have some of those qualities?

Rachael Truchil, MD, MPH: Yeah, so varenicline actually works on the nicotine receptor and so it kind of creates this ongoing activity so that your brain is like actually tricked into thinking that you're still smoking even if you're not. And it helps to prevent having withdrawal if you stop smoking. And also when patients take varenicline, they just don't enjoy smoking as much.It's just like you don't get the same benefits, of it. And so you end up starting to smoke less. And then that kind of lessens your overall nicotine dependency.

Host: Very pragmatically, how do you prescribe it? Do you have to dose titrate it? Do you start it at a specific dose and leave it there?

Rachael Truchil, MD, MPH: Yeah, so varenicline, comes in one milligram tablets and you can get it, you know, the trade product Chantix actually comes in a blister pack, but I don't tend to prescribe it that way. I prescribe it as one milligram tablets. And I, actually have a dot phrase, that I put in for patients, after visit summary that just says, take half a pill for three days.

Take a half a pill twice a day for three days, and then go up to one milligram, a whole, tablet, twice a day, therein. And the old kind of thinking was that patients should set a quit date and you should start Chantix two weeks before that quit date to make it easier when you get to that quit date.

But really now it's like quit date aside, you just start it and patients do smoke less with it and often find their way to abstinence.

Host: One of the points I make with my patients is that smoking less matters. It's not an on or off. That the effect on the body is really sort of a dose response effect over time. And, that the less you smoke, the less risk of all the complications of smoking. The less risk you'll have for all those complications.

Rachael Truchil, MD, MPH: And I mean, really the same goes for nicotine replacement therapy. So for, people who maybe don't want a pill or haven't tolerated varenicline because it's caused them nightmares or headaches or some other side effect, nicotine replacement is the second line option that works well. And you don't have to be completely ready to quit.

You can just slap on that nicotine patch and because there's some nicotine, that is exogenously being put in your body, when you do smoke a cigarette, you don't get as much benefit. And so that kind of psychologically helps you to smoke less, even without intending to, and there's a lot of nicotine replacement products on the market.

Host: I want to ask you the details of these nicotine replacement products. I practiced inpatient medicine for many years. I was familiar with patches, which we prescribed. But there's gums, there's lozenges, there's a nasal spray, there's a mouth spray, there's an inhaler type of variety, right? Or some sort of cigarette, like one. These are all over the counter now. Is that right?

Rachael Truchil, MD, MPH: So you have to get the nasal spray and the inhaler through a prescription. But patches, gum, and lozenges are all available over the counter. The mouth spray is not yet, available in the US. It's available in Canada, and probably in the next year or two will come to the US.

Host: Can you give, us a sense of the relative potency of these? Like for instance, with the patch, you have to kind of choose a patch 7, 14, 21 based on how much roughly they smoke. I suppose when it comes to the gum, people just take it as they need it. So it's not so much you have to tell them how much to use, but maybe these others have, it's helpful for you to know a dose.

Rachael Truchil, MD, MPH: Yeah, absolutely. So I generally think about one 21 microgram patch as being equivalent to one pack of cigarettes a day. And 14 micrograms is half a pack and then less than that is seven micrograms. So if patients are smoking two packs a day, they really should put on 2 21 microgram patches at the same time.

And so that's the dosing. The lozenge and the gum come in two milligram and four milligram, and it actually, by the recommendations is supposed to be your time to cigarette in the morning. And so for patients who smoke a cigarette less than 30 minutes after they wake up, then you should be recommending the four milligram, lozenge gum.

And if it's over that, then you do the two milligram. In clinical practice, I don't usually follow that. I usually will, just do two milligram gum and lozenge and tell patients to really not wait until they get a craving. You're supposed to keep using it, nine times a day throughout the day to get extra nicotine in your body because that way when you smoke, you get less benefit from it.

And it's this like negative reward pathway. But with the gum and the lozenge, you have to teach patients how to use it correctly or else it will not work. It will make patients nauseous. And so gum, you chew it, you park it, in your cheek by your gum, and you wait until it tingles and then the patient has gotten some nicotine and you can chew it again and keep doing that.

The lozenge, you just park it, park in your cheek and let it dissolve. And they're available in different flavors. Some people prefer one versus the other. But the nasal spray, I cannot, emphasize enough that it works really well. And so if your patients say, you know, I can't chew gum, the lozenge makes me nauseous, the nicotine nasal spray, you have to get a prescription for it.

And sometimes you have to go through a prior auth, which is actually very easy if you just say they have not tolerated the other forms of nicotine replacement. But the nasal spray patients really like, kind of bypasses the mouth.

Host: The nasal spray, is it similar that you dose it when people would have a cigarette or do you do it like Flonase or something that?

Rachael Truchil, MD, MPH: No. So it's the same as with gum and a lozenge. You want to do it like, eight to nine times a day, and then again, with cravings. And again, you just have to teach patients how to use it. It's not like Flonase, you don't want to like sniff it into the sinuses. You want it to be absorbed right into the nasal mucosa.

And, one spray each side equals, the standard first dose. And I always tell patients that it burns a little at first, and so as long as they're prepared for that and know that that will go away if they just keep using it.

Host: So,

are there other options or is that these have sort of risen to the top as the best options? I mean, varenicline first line, oh by the way, can you use them together? Can you use varenicline and nicotine replacement or do you do one or the other?

Rachael Truchil, MD, MPH: So, I don't know about you guys. Maggie and Ashish. I will say, I don't think you're by the FDA recommendation, supposed to use them together, because they kind of work on the same receptor and, and it doesn't, make a ton of sense to use them at the same time. Although I will say that for patients with very severe tobacco use disorder, who are really struggling, I certainly will double up and have them use varenicline and nicotine replacement at the same time.

Margaret Lowenstein, MD, MPhil, MSHP: Yeah, I would agree. I think of like, sort of a long acting, being one of those two. And then if, one is not effective at kind of cutting back, I'll go to both and then I try to do some sort of short acting, whether it's the gum, lozenge, the nasal spray for cravings. Since your grand rounds, I have also been prescribing more nasal spray and having good success.

Host: So, just to finalize that point and sort of summarize Rachael as I understand it, varenicline is number one. The nicotine replacements are number two. Bupropion we used for a while. I think it's been maybe largely replaced by varenicline. But it may still have a place. Is that right?

Rachael Truchil, MD, MPH: There are certainly patients who don't tolerate varenicline, and I think that bupropion plus nicotine replacement would be my second choice of regimens for those type of patients.

Host: And you mentioned tolerance of varenicline. I think it's important to touch on that, because, there is this idea of it having sort of psychiatric effects and so forth. Where are we at with that now?

Rachael Truchil, MD, MPH: I think it's largely believed to not have an impact on psychiatric comorbidities. And so we used to be very cautious about it. There had been a black box warning, but I think largely that has been shown to not be an issue. And so what I usually tell patients, and I don't know what you guys do, but I tell patients that, if your mood changes at all on these medications, if you have any unusual feelings, after starting varenicline to stop immediately and let me know.

But in general, I consider this first line for patients who have bipolar disorder, even schizophrenia and other severe psychiatric disease.

Ashish P. Thakrar, MD, MS: I'm pretty sure that black box warning was removed. And so, exactly like you said Kendal, I think it's been shown that that association was spurious. And I think the side effect that I come across much more frequently is, really vivid, sometimes bad dreams. And so I think it might be helpful, to share with your listeners on some approaches we might have for how to address that.

Because varenicline is really that effective, in how we kind of dose titrate. I'll just share my approach to this is to be flexible with the dose of varenicline. For most people, we say starting goal dose is one milligram twice a day, but that doesn't have to be the dose for all people, and that's not the only dose that's effective.

So for some people, most of the time I'm going down on that dose because people say they're not tolerating one milligram twice a day. And you can take a milligram once a day. You can change how you do it. Some people you can even go higher on the dose, I believe. and so, yeah, wanted to share that.

I don't know if Rachael or Maggie have other approaches.

Margaret Lowenstein, MD, MPhil, MSHP: Yeah, I do something similar. I think I tend to start with the kind of typical dosing that you both described. I guess I think also just warning patients, because it can sometimes be, you know, you don't want to freak people out and not think that they don't want to use it. But I, think just, alerting them to this potential side effects so that they're not caught off guard.

And then for some people sort of, huh, that's interesting. It's not a huge deal. For people who find it really disturbing, I think adjusting the dose. Sometimes I've used like melatonin or other sleep aids to try to see if, you know, safe sleep aids, to try to see if that helps, if they're kind of having trouble staying asleep.

But in general, I think with some adjustment you can get patients through it. And you can't, then maybe switching over to the nicotine patch as my kind of long acting treatment. exclusively.

Host: So before we leave tobacco, I want to talk about vaping because I, like many people, I think is very confused about vaping. First of all, it seems to come in different forms. I see them lying on the, you know, people doing it. Also, these pens and other things laying on the street. And so, so, the main questions to address here is, first of all, how does one vape, what do these things look like?

Second question I want to address is, is this safe? Is it safe in general as opposed to not vaping and the third question is, is it just better than cigarettes and potentially could be used as a harm reduction strategy? So I want to tackle those three questions and any others you guys want to throw in there.

But Rachael, maybe we can just start with vaping in general. I think most of us probably have seen folks with the vape pens. I've seen people with cigarettes that look like cigarettes, but apparently are not cigarettes. And when you look closely, you notice they're not. And then on your slide, you also had a modular form, which is a little bit more of sort of a heavier thing.

Looks like a, AirPod case a little bit with a trumpet on the top. And then a pod based form. So there are these four sort of things out there that one could use to vape with, right?

Rachael Truchil, MD, MPH: Yeah. So, most of the time I see patients using the modular form or the pod based vapes. And, they range from, you know, single use. You use them until they're completed and then trash them. Some are more sophisticated where you can add pods to them that, you can refill the pods and then, continue to vape using the same device.

 But there's lots of varieties. There's lots of marketing. There's lots of flavors. So people have lots of different options.

Host: And what's in them?

Rachael Truchil, MD, MPH: So the actual ingredients are nicotine, and then propylene glycol is the propellant. And that helps to create the vaporization of the nicotine and then the flavorings.

Host: Okay, so nicotine's in there. I'm going to ask a very stupid question that I know should know the answer to, but I actually don't. Is it nicotine that causes all the downstream negative effects that we saw with tobacco use, with smoking, or is it other things that are in the tobacco tar?

Rachael Truchil, MD, MPH: Yeah, so nicotine itself is not super harmful other than it does have a vasoconstrictive effect. And so that can cause some issues with wound healing and also some, downstream vascular issues. But, in general, the negative effects come from everything else that is jam packed into the cigarette; the tar, and, the chemicals.

 So really in thinking about combustible cigarettes versus e-cigarettes or vapes, in thinking about like the safety profile, you have to ask yourself, what are you getting when you smoke a vape versus an e-cigarette. And combustible cigarettes have carbon monoxide just from the combustion.

They have oxygen gases and tars. And they also have volatile organic compounds, which are thought to like be, the carcinogenic property of cigarettes and also heavy metals. So e-cigarettes have an order of magnitude, kind of less volatile organic chemicals and heavy metals, but they still have them present.

And so I think just understanding that there are still some chemicals that your body's being exposed to, but it's definitely less than combustible cigarettes. In addition to the propylene glycol and the flavorings that are being vaporized.

Host: So we should still worry about it, but certainly not quite as much as we would've worried about tobacco.

Rachael Truchil, MD, MPH: So I will say that I never recommend that patients vape. I don't go out of my way to kind of suggest that this is much safer. I stick with varenicline as first line nicotine replacement, as second line and go from there. But some patients just like are not interested in using those treatments.

And a lot of patients are already vaping because sometimes it's really inconvenient to smoke. You know, you're in a non-smoking work environment. You're at home you don't want to expose your family to the smell. So, people are already vaping. And then thinking about it, not so much as like a, I'm treating you and recommending that you go out and buy a vape, but like from a harm reduction standpoint, vaping does appear to be safer than combustible cigarettes, not harm free.

Margaret Lowenstein, MD, MPhil, MSHP: I do something very similar, but I think just to chime in, that I think because e-cigarettes or vapes are a little easier sometimes to use in public places or indoors or whatever, sometimes for those who kind of switch over, they're actually end up smoking or vape, or they may vape more frequently than they might have smoked.

And so I think sometimes if I'm talking to folks about it as a harm reduction strategy or kind of in this case, like just sort of reminding them to try to push them a little bit to say like, use it as a replacement for times that you would smoke more similar to what you do with like a lozenger or the gum than to just be like, cool, I'm going to vape all day. Cause I think that's the risk potentially in kind of increasing your nicotine dependence or your exposure. But I do something very similar to Rachael in practice in terms of using it as like, you know, not first line, but can be helpful for people as a tool.

Host: And it is a legitimate nicotine replacement therapy, right, that has been shown to be beneficial in people trying to reduce cigarette use. Right?

Ashish P. Thakrar, MD, MS: Absolutely. It's shown to have quite strong effects for reducing cigarette use.

Rachael Truchil, MD, MPH: Yeah. No, and to piggyback on that, I always tell patients, you know, if our goal is to reduce your exposure to these harmful chemicals that I want you to get to, just vaping, not combustible cigarettes and vape at the same time, I think when you look in at the level of exposure, it's pretty similar if you take somebody who's vaping and using combustible cigarettes to just combustible cigarettes.

And so really if we're kind of doing this, I'm saying you got to completely replace the combustible cigarettes with vaping.

Ashish P. Thakrar, MD, MS: And I think I'm also adding something else to that conversation as well, which is that I want to make sure patients are oriented towards thinking about what the next step is because I don't know what the effects of vaping for 10 or 15 years really is going to be on their lungs or on other potential risks to their health.

And, so that's not the end of the conversation. That might be the intermediate goal and maybe that's where we're going to be for the next six months or a year. But I think thinking about what the next step is going to be, and at least priming patients to think that that isn't the end goal. Because there are still some harms associated with vaping and it's still unknown what I think some of the long-term consequences are.

Host: And you still regard other forms of nicotine replacement therapy that we talked about as being a safer alternative to even vaping. Right?

Rachael Truchil, MD, MPH: 100%. And also if somebody is trying to stop vaping, then I fall back on all of the usual things like varenicline and nicotine replacement therapy.

Kendal Williams, MD (Host): Oh, that was a question I was going to ask Rachael. For folks that are vaping, you can also use these strategies. Yeah.

So before we leave nicotine and tobacco generally, and any final points to make?

Rachael Truchil, MD, MPH: I think, we just need to prescribe these medications more. I mean, smoking is, a really significant influencer of patient's health and trying to get these treatments that are evidence borne out more is really important. I think if patients are not ready, don't want medication, slapping on a nicotine patch can really help.

Host: That's great. I need to do more of this. I recognize it and this is really helpful, and just having this discussion, I, and I'm hoping it's helpful for others to give some practical to's on their hands so that it doesn't seem like just the barrier for us as providers is low to go ahead and prescribe these medications.

Rachael Truchil, MD, MPH: And I guess the one last thing is, a lot of patients feel like they can't use nicotine patches if they're smoking. Like that, they have to rip off the patch if they're going to smoke a cigarette. And that's not true. So, you know, you keep a patch on and it's okay if you smoke, because that is how it's actually going to work and help you to smoke less.

 Some patients will have some side effects if they have high doses of nicotine. They may feel a little bit dizzy or nauseous, but it's not a contraindication. They don't have to take off the patch.

Host: That's great. That was a great discussion. Very helpful. So let's turn to alcohol now. And this is also very common in our practices. I've managed, three or four alcoholics in the last couple months. So this is really helpful. So, the case that set up this discussion within your talk was a 53-year-old female with alcohol use disorder who drinks three to four glasses of alcohol daily when she gets home from work. She's interested in medication. She did not tolerate oral naltrexone. She did not tolerate IM naltrexone. She's not interested in abstinence. Actually, Ashish, before we get to the treatments strategies, I want to ask you, what do we regard as a safe amount of alcohol use nowadays?

Ashish P. Thakrar, MD, MS: That's a great question. I think more and more evidence has come out over the past few years showing that any exposure to alcohol can have negative effects on health. And I think a lot of this research more recently has focused on some of the carcinogenic effects of alcohol exposure.

So, there was a thought in the past that some exposure in low quantities to certain kinds of alcohol, certain kinds of wine, might, have some cardiovascular health improvements. But it seems like that's most likely was an association between who was drinking in that amount and those types of alcohol and that, the latest research seems to suggest that any exposure to alcohol has some negative consequences to health, but that those consequences become much more pronounced once you get over 14 drinks, a week, or when you're binging, which in the US we define as four more drinks for women, or five or more drinks at a time for men.

Host: Yeah, I just wanted, it's a little historical comment. I was ironically doing my master's in public health when I think it was the American Heart Association, came out with a statement saying that, one to two drinks of alcohol a day was actually beneficial. And it was framed in this way that, you know, many people enjoy this and it's just part of the context of many cultures and so forth.

And we have probably been too zealous in our prohibition against alcohol from the medical community. And we're now saying that one to two drinks a day is safe and effective and even maybe encouraged. So that was when, and I remember when that came out and we were like, oh geez, that's not sure about that.

But I think Ashish, what's changed since then is while there may be, this is my understanding, while there may be some positive heart effects, it's this cancer piece that we didn't appreciate that you're really canceling out all those positive cardiac effects with this increased cancer risk.

Both generally, but also I think in breast cancer, in women, there's been some studies that are shown in particular, right?

Ashish P. Thakrar, MD, MS: Yeah, I think that's exactly right and I think we can acknowledge that alcohol can play an important, and for some people beneficial role in their life overall. It, there are things that it does to help increase sociability and people interacting in person more, which we could all use more of in our lives.

I think we can acknowledge that. But when we are focusing on the effects on health from a medical perspective, I think, the thought has kind of now shifted more towards that any exposure, the harms to the health seem to outweigh what some slight cardiovascular benefits exactly like you were saying.

Host: Yeah. And so then the amount of drinks, and by the way, when we say a drink, I was taught, one beer is equal to, one shot is equal to one glass of wine in rough approximation of the amounts of alcohol. I assume that's still true. I don't really follow the alcohol industry, nor do I drink personally.

So I don't know these things. But so we can just tell people whatever you're drinking, it's one of those. And we start to see negative effects clearly at up over 14 a week.

Ashish P. Thakrar, MD, MS: I think that's true. Beers have had increased, ABVs, alcohol by volume over the past few years. So, that's just something to keep in mind. You know, a 12 ounce volume of beer, which I think was typically considered standard used to be, maybe three to four, maybe 5% alcohol and some still are. Many now are upwards of seven, eight, 9%.

So it, I think paying a little bit close attention to that as well. Also, when we talk about a glass of wine, it can depend on how big that glass is, right? How big you it.

Host: Right. Exactly. Yeah. Yeah.

Rachael Truchil, MD, MPH: I think that patients ask a lot about this because it's been in the news. And I think the bottom line is that it's probably not safe in any amount, but if you are going to drink, then we should be doing it within those guidelines that you mentioned.

Margaret Lowenstein, MD, MPhil, MSHP: And I think that the risk going up with higher consumption or the binge drinking that Ashish mentioned, I think some of the health risks go up substantially after you drink over those guidances of like 14 drinks in a week for men, or seven in a week for women.

So, I think we're finding that this idea that like lower amounts is totally safe or even helpful, like that has been debunked. But that, I think when we think about risks around, you know, liver disease, trauma, other kind of serious effects, those do go up at the kind of limits that we were all taught in school.

And that's really where those are derived from. So, seven drinks a week for a woman or a man over, I think it's 60 and more than 14 for a man under 60 is still kind of, that's like a sort of heavier drinking cutoff.

Host: Yeah. And you mentioned trauma, Maggie. I mean, I think that the alcohol fuels, it can be part of a propellant for violence and domestic abuse and all kinds of these problems that we have. And alcohol is often a propellant in those circumstances.

Alright, so with that introduction, this individual drinks three to four drinks, a night, which we've established is higher than is ideal, certainly for a woman. But has tried other things, has tried naltrexone, has tried IM naltrexone. And the question is how do we decide about our options?

Ashish, I'm going to set it up here. I know that, disulfiram is not recommended necessarily that much anymore. But we still have naltrexone. We still have acamprosate, and now we potentially have topiramate or Topamax out there as an option. Right? And how do we sort through what would be the best option in any patient?

Let's just, this lady's tried naltrexone, but let's talk about a naive patient and see what would you recommend?

Rachael Truchil, MD, MPH: So before I let Ashish talk, I just want to give a shout out to disulfiram because, I think there is a time and a place for it, you know, for patients who are interested in abstinence, and want the control of knowing that that is going to be the treatment for them. And if they have a partner or somebody at home who can watch them and make sure that they take that medication in the morning, I think it can be super helpful because once you take disulfiram in the morning, you know that alcohol is off the table.

And so it can really help with cravings in that patient population. And so I would just give a shout out for some patients with d.

Host: Yeah. And just to say it out loud, disulfiram is Antabuse. It causes a very unpleasant reaction if it's in your body and you drink alcohol, right Rachael?

Rachael Truchil, MD, MPH: Correct. And you have to give all sorts of advice with taking it, you really can't consume any alcohol. Even, like if you're having some mouthwash with alcohol in it, there's lots of, caveats that you, want to talk to patients about. But, it's a good medicine for some patients.

Host: So let's talk about naltrexone. Because I think that's the second thing most of us think about. Ashish, you, there's, you can take it by mouth. You can give it, IM, tell us about naltrexone.

Ashish P. Thakrar, MD, MS: Yeah. So, naltrexone is the medication that has, I think, the strongest evidence for efficacy for both reducing drinking and for helping promote sustained abstinence. It's once daily tablet, typically dose 50 milligrams once a day. Some people end up feeling a little bit nauseated with it.

So some you can start with 25 milligrams, just as like a short little ramp up, one or two days. See how they tolerate it, get their body used to it, and ramp up to 50 milligrams. The number needed to treat for abstinence is, think it's about 20 or 22, somewhere around there and for reduction, pretty good.

Yeah. And for reduction in heavy drinking, I think about 11 to 13, somewhere in that range. I can't remember the exact number. So it's pretty good. And considering how well it works, it is woefully underutilized. So I think if I can pass on one recommendation to the listeners, it's please strongly consider medications for alcohol use disorder.

Naltrexone, I think is typically considered first line by most people, because it's just has such strong evidence across so many different settings. Besides the oral version, there's also an extended release injectable version. It's given once a month injected into the muscles of the butt most often.

I don't know if it can be given elsewhere. I've only ever heard of injected there. Yeah. Great medication. I think we should be offering it to all patients. You asked about what we would offer to patients who don't tolerate naltrexone. And I think if you talk to a bunch of different experts in the space, you might get slightly different answers.

I think the answer I'll give is that I consider topiramate or disulfiram to be really good options, depending on the situation. And I might even promote one of them to first line alongside naltrexone also, depending on the situation. So, I'll start actually with disulfiram, just to mention it's one of the oldest medications we have for alcohol use disorder.

It was one of the first, probably the first that was approved, I think it was FDA approved probably in the fifties or sixties, a long time ago. Since then, there has not been a ton of strong evidence to show that it works. But part of that, seems to be because of how it was tested. And I just want to give a shout out to Steven Hole at Yale who's kind of changed my thinking about disulfiram.

And he recommends thinking of it as a behavioral treatment. And because in many ways it is, it's not changing cravings, it's people kind of thinking that and knowing that they can't really drink. And so it's really hard to compare to a placebo because if you give a placebo, it's going to have the same effect by definition.

The summary with disulfiram, as Rachael mentioned, is that it seems to work really, really well if we can ensure that patients take it. And so that's either in a monitored setting, residential drug treatment or alcohol treatment program, or if you have, someone to help support that patient at home, who often who lives with them, to ensure that they're taking it.

But it works really, really well if you have that. And then, topiramate, is another medication that seems to work quite well, for alcohol use disorder. I don't understand the exact mechanism by which it works to reduce cravings. But if titrated to goal dose, which I generally think of as about 200 milligrams a day, it can have a quite profound effect at reducing cravings to drink.

Rachael, I know you presented the slides on topirimate, so I want to invite you to share.

Rachael Truchil, MD, MPH: Yeah, so I think the mechanism is that it's active at the GABA receptor and so that is how it reduces cravings for alcohol. And I think it's just, you know, at least when I went to medical school I was taught, that naltrexone, acamprosate and disulfiram being the big options for alcohol use disorder.

But topiramate is a good option that we should think about, especially, if they didn't tolerate naltrexone or if they have a seizure disorder, that's a good opportunity to try it as well.

Ashish P. Thakrar, MD, MS: And if I can just mention about acamprosate, which, listeners might be wondering why we aren't mentioning more. It's challenging in I think two different ways. One, it's three times a day medication and each time you take it, you actually have to take two tablets. So I think it's really hard for people to remember to take three times a day meds.

It's really hard to take six tablets a day. It also does have some side effects. It can cause diarrhea, for a lot of people. So I think for practical reasons it can be challenging. And then from the evidence perspective, there just seems to be big conflict between studies done in Europe and studies done in the US. Studies done in Europe seems to suggest that it works similar effect size as naltrexone. Studies done in the US don't seem to find that.

And some of the authors of some of these studies when I've heard, discuss this, attribute that to the setting in Europe. A lot of these studies were done after people finished, medically managed withdrawal and were in kind of early abstinence for weeks and then started acamprosate. Whereas in the US most of these were started like right after someone stopped drinking sometimes while they were having alcohol withdrawal.

So when I think about using acamprosate for someone who hasn't tolerated one of those other meds that I would consider first line, naltrexone or maybe disulfiram or topiramate and if they've had at least a few weeks of abstinence and we're trying to sustain that. So I'm trying to mimic what was done in the European studies.

Host: Just to get to the practical side of this, topiramate you mentioned, if you wanted to start that you would start at 25 milligrams, and then you'd go up by 25 milligrams a week until you reach the goal dose of 200, right Ashish?

Ashish P. Thakrar, MD, MS: That's how I would do it. Once I get to 25 and then 50, I'll actually titrate by about 50 a week.

Host: Yeah.

Ashish P. Thakrar, MD, MS: Because at that point I'm using the 50 milligram capsules, I don't go by 25

Kendal Williams, MD (Host): Right.

Right.

Ashish P. Thakrar, MD, MS: Do it in a way that is like more feasible for my patients.

Host: Yeah. Disulfiram is a once a day dose, right?

Ashish P. Thakrar, MD, MS: That's correct. Yep.

Kendal Williams, MD (Host): Acamprosate you already mentioned. Naltrexone is also once a day, I believe, right?

Ashish P. Thakrar, MD, MS: is once a day. Exactly 50 milligrams once a day. There are some small studies suggesting that people don't respond to 50, might respond better to a hundred. So if they're tolerating it, you can consider, you know, and people are saying they have some effects, but they just want more. You can try going a hundred.

There's also some studies suggesting that 25 milligrams might be enough for a lot of patients. So, similar to my suggestion for varenicline, you, can consider, those different dosing approaches for someone and tailor it to the patient in front of you.

Margaret Lowenstein, MD, MPhil, MSHP: One like theme, maybe I'll just pull out from what everyone's been saying that I think is relevant to a lot of what we do in addiction care and also different than the way that I was taught a lot of the time, is that for many of these medications, it's important and great and effective to start them, even for folks who aren't quite ready to stop.

Certainly, the disulfiram being an exception, you don't want to give that to someone who's drinking. But I think when we're talking about like there's evidence for things like naltrexone for reduction in drinking or starting the smoking cessation treatment before people are totally ready to stop.

That's true for opioid use disorder as well. So just to kind of like maybe zoom out for a minute. I think that's an important paradigm shift from the way that I was taught for a lot of these. And, there's still a lot of benefit in reduction of all these substances, so I'll just put that plug in now while we're thinking about it.

And for naltrexone in particular, it's not a ton of data, but there's a little bit of data to even support like a PRM use of naltrexone. So I've used it in patients who maybe have social situations where there's alcohol that's going to be present and they can't avoid, you know, otherwise they're doing okay.

But when they're in these situations, it's very hard not to sort of start drinking and escalate. And that's a great use for that. So again, that's not the sort of FDA approved dosing, but you can get creative with it. And, so even for folks who aren't necessarily ready to be abstinent completely, these can be effective treatments still.

Ashish P. Thakrar, MD, MS: I'd also like to complicate this picture we sometimes paint of like, okay, what stage of change is someone in as if it's, something that's kind of fixed in that moment and as something that's consistent.

I think the state of having an addiction or use disorder is one of constant ambivalence, and that ambivalence is often roiling internally in someone and they might flip in and out of different motivations to change, dozens of times in the day before they're using, while they're using, after they're using.

There's guilt anticipation. All of that is like mixed in. So a lot of this can come down to how we as the clinician frame a conversation and you know, inviting them to share how they're feeling about their relationship to the substance and trying to understand what is motivating both their ongoing use and motivating the negative feelings with their relationship.

Because if this is a use disorder, there are negative consequences and there are somethings that aren't working well. And if we can understand that, we can kind of move beyond the simple, like, okay, are you ready to quit? Are you not ready to quit? It's often a little bit more ambivalent. And it's kind of on us to try to understand that and harness that I think.

Margaret Lowenstein, MD, MPhil, MSHP: And I'm just going to piggyback on that more. Because I think this is something we all feel really excited about. Because I do think, and again, is different than the way that we were taught, but I, completely agree, Ashish. I think, that, that teaching is a little bit artificial and I think both for the patients and for us, it's helpful to sort of, not see this as a black and white topic.

I think people, if you give them tools that help with their craving, that help with their reduce the reward when they do use, or, some of these medications we're talking about work in different ways, but sort of across the spectrum, when you give them those tools, it's actually then easier to become more ready to change as opposed to sort of waiting for that perfect moment.

Like if you actually give somebody something that's going to help make their cravings less, it's easier to think about, okay, maybe I can use less as opposed to sort of the other way around. And then also as a clinician or a patient, if we focus completely on like, okay, my goal is to stop drinking or stop smoking or whatever, and then they fall short of that, but they still make huge improvements.

This also provides a sort of a better framework, I think, for how we talk about this with patients and how we feel we're doing as doctors. Because like I know, you know, I have patients I've been treating for substance use disorders for sometimes months or years who continue to use, but have seen all sorts of benefits, right?

Like, they're more functional with their family, their job, their health is better, like all sorts of things. But if I just said, okay, are you still drinking sometimes? Like the answer is yes. Or whatever substance. And so I think that just, there's good opportunity to build that discussion that Ashish is talking about. That's kind of, you know, these are sort of foundational topics in motivational interviewing.

But I think just practically speaking, like, as we talk to patients, these can be great conversations and they can also really build alliance and trust with clinicians that they see that maybe they have not had in the past when they've felt judged or, okay, you're not ready to go. Great. We're moving on.

Host: So, just for our audience, I want to let everybody know that we're going to do a part two, because we're obviously not going to get to the, all the topics we had hoped to get to in this discussion. So we're going to bring everybody back and we're going to talk about alcohol withdrawal and then the fentanyl epidemic and how to manage that.

But before we leave alcohol, I want to talk about something new or ask you about something new, and that is the biomarkers for alcohol use and getting a sense of, how much people drinks. You know, just a historical note, I remember doing the alcohol substance abuse clinic at the VA when I was training.

And, the experts there, some of my great mentors would use GGT, as the liver enzyme as the way of assessing whether or not somebody was drinking. But now we seem to have something better, and that's PEth, right? So phosphatidyl ethanol, and we're now using that to assess whether people are actively drinking, right?

Ashish P. Thakrar, MD, MS: That's exactly right. I'm so happy you were the first one to pronounce it because I have a tough time saying the full name. Phosphatidyl ethanol, PEth is how I'm going to refer to it from now on. Fairly new. And, it is a pretty good biomarker for alcohol exposure, over the two to four weeks prior to when the blood was drawn.

So, red blood cells, when ethanol's present, they end up building up this phospholipid on, the outside of them. And, it's this phospholipid, it's phosphatidyl ethanol PEth and the more alcohol someone's exposed to, the higher the PEth level. And as I mentioned, it reflects past two to four week exposure to ethanol.

Despite red blood cells living longer than that, I don't quite understand why that's the case, but two to four weeks and, it has really high specificity. So, we know with quite a bit of confidence. I think specificity is essentially a hundred percent. The only false positives seem to be from recent blood transfusions, if the blood was transfused from someone else who was drinking. Sensitivity is also quite high for heavy use, it's about 95% sensitive and we typically use greater than 200 nanograms per milliliter as the cutoff for heavy use. And zero to 20 is minimal to no consumption. And greater than 200 considered heavy consumption.

So yeah, it's now available. I'm using it more and more in my practice.

Host: When I first came upon it, it was still somewhat experimental and you know, as is in many of these circumstances, the residents taught me about it and said, we're going to order this. And I said, what's that? And they said, well, it's still experimental, but we're, it's very good. So zero to 20 considered no or minimal consumption, 20 to 200 is somewhat moderate consumption. And then anything over 200? Yeah, I had a lady this weekend that we measured her PEth and it was over 200.

Rachael Truchil, MD, MPH: I also think it's just worth mentioning that it's a good idea to have a conversation about this test before you actually get it for somebody because, there can be consequences of seeing it on the chart. And the way I usually will discuss it with a patient is I'll say, you know, I want to see how much alcohol your body is being exposed to.

And this can be helpful for you to know as well. And also when you're starting a treatment to be able to check a PEth and then after you've been on the treatment for a couple months to recheck it, can really give you information about how helpful the medication maybe has been, especially like in a setting where maybe the patient's goal is not complete abstinence at that period of time.

Ashish P. Thakrar, MD, MS: I think of it like the PHQ nine in that way, right? For patients who I'm using SSRIs on, I'm trying to get PHQ nine somewhat regularly and I'm trying to trend. and like exactly like Rachael said, especially for the people who are, whose goal isn't abstinence. Most of the patients who I have in my clinic who I'm treating for alcohol use disorder, they tell me their goal is abstinence, and they'll often tell me what I think they think I want to hear, which is rosier picture, than what they're actually being exposed to.

So I have found it very helpful again, with their consent, as Rachael said, starting with the conversation, but then getting it and helping use that to guide how things are going and to start the conversation, maybe the next visit to say, Hey, you said things are going really well, this is what this test shows, you know, what are we missing?

Um, how are things really going?

Kendal Williams, MD (Host): The PEth seems to be fairly available, right? It's definitely in the Penn lab, Quest and, LabCorp have it as well?

Ashish P. Thakrar, MD, MS: Yeah. And I'm quite sure Quest does as well. Medicare reimbursement is $114.

Host: Okay.

Ashish P. Thakrar, MD, MS: So it's

not

most

Not the most

Host: But yeah. Okay, good. That's great. Well, this has been terrific and, about halfway through this I realized we're going to have to bring you back for part two because there's just too much content here for us to cover in one session. So I really appreciate you all coming.

Before we leave, sort of the tobacco and alcohol discussion of our addiction series, any final points?

Ashish P. Thakrar, MD, MS: I just wanted to make one point about the alcohol use disorder treatment. We focus on medications, those are the tools that we're most comfortable with as internists. There's such strong benefit to other forms of treatment for alcohol use disorder as well.

And, peer support groups, peer recovery groups, which AA is the most well known, but it's not the only one can have a profound effect to help people struggling with alcohol addiction. So, I just want to make sure that we don't narrowly focus on the carpenter with our hammer.

Like we're internists and we think about medications, right? When there's this entire world of behavioral treatments that can, and often like life changing for people. So, we should not make those necessary before we start medications, right? We should, if we have patient in front of you, start medications and think about these other forms of treatment.

So peer support groups. Often using 12-step approaches, but I don't always, AA is one of them. Smart Recovery is another more secular option. And then there are other forms of behavioral treatment such as outpatient counseling, outpatient based individual and group therapy, intensive outpatient, and then all the way up spectrum of intensity to residential treatment. All of which can have a really profound effect for people beyond the medications.

Host: Maggie, Rachael, any final thoughts?

Margaret Lowenstein, MD, MPhil, MSHP: I was just going to say, I'm going to reinforce the point that I've already made, which is that, and we've all already made, but don't wait to offer treatment. I think that's like if you take away one thing kind of across the spectrum, and, feel comfortable asking and, talking to your patients about, these very common but like highly morbid conditions, in a way that's, non-judgmental and open, 'cause I think that will really help you to be able to move these conversations forward. The other thing I'm going to share, we haven't talked about yet, but I always want to plug our Care Connect Warm Line, which is a resource we developed at Penn. It's a seven day a week, telehealth line that can be called by patients or providers who are seeking help for substance use disorders.

Maybe Kendal, I don't know if they're show notes, but the phone number is (484) 278-1679. So for people in Penn or across the Philadelphia area, it's a number that you can call, if you're just like I am looking for treatment for any type of addiction or resources or harm reduction, they may not be able to solve every problem over the phone, but they often are a great place to start, whether you give it to patients or you're a provider who is like, I need help with something.So just plugging that always at every time.

Host: Maggie, even if we forget the number and we always Google stuff, if you Google it, you'll get what Penn?

Margaret Lowenstein, MD, MPhil, MSHP: Just Google Care Connect warmline or go to penncamp.org. That's Like Penn, C-A-M-P, like Center for Addiction Medicine and Policy. And again, this is something we started as a buprenorphine telehealth prescribing program, but now has expanded to provide all sorts of resource navigation. And so I think I just want everybody to have a low barrier way to get help.

Rachael Truchil, MD, MPH: And I guess my last note is to all the primary care doctors who get frustrated when patients return to using which happens because addiction is a really severe disease. And patients often will return to using or have a slip and, just know that coming at it with a fresh mindset every time you see a patient, can really improve their trajectory long term.

And every time patients show up and say, I want to try again, they're more likely to succeed that time. And so just to not get discouraged and to keep working with patients.

Host: Rachael, that's a great way to end. I love that. So thank you all for coming on the podcast and addressing these very important topics, which are incredibly important for all of our, primary care population and all of our primary providers to help manage. Again, we're going to do a part two, we're going to bring you back, and we're gonna tackle some of the heavier side of this, and maybe shade it a little bit more towards inpatient.

But, I really look forward to that. So I want to thank our experts today, and I want to thank the audience for joining the Penn Primary Care podcast. Please come back again next time.