Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. This podcast is Narrator - ? 00:12 provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice, and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk episode 170 I'm your co host, Dr. Kane. Dr. Khyati Patel 00:35 I'm Dr. Patel and the title of today's episode, number 170 is hope and healing overcoming opioid use disorders through evidence based therapy. We are, together with our faculty colleague, Dr. Roberto Dumais, we are discussing different pharmacologic options evidence for the treatment of the opioid use disorder. We'll be referring this to o, u, d time and again as we talk about it, and the role pharmacists play in assisting patients who suffer from oud, and Dr. Dumais does fantastic job at FHCC Next Door, serving the patient. So Dr. Dumais, thank you again for joining us, and you know, sharing your expertise. You know this is an important issue we face in the country. Can you tell us specifically, how are you involved in the treatment of opioid use disorder patients at the VA? Speaker 1 01:30 Well, first of all, thank you again. Always a pleasure to be a guest here on the podcast. So thank you so much for having me. I think something that is really interesting right now that what's happening in terms of our involvement in terms of clinical pharmacists, and what we can do with oud and treating opioid use disorders and the opioid epidemic in the country is that we can be really at the forefront and definitely within the VA setting, pharmacists have an active role, specifically for me and my colleagues at my clinical sites, we are actively involved in what's which we will talk about later. Are things called like suboxone inductions to start patients on medications for oud, or for short, M, o, u, d, so we can identify dosing and do closer follow up and monitoring for patients who have OUD and kind of personalizing their treatment plans for them so they can have normal lives, just like you and I. So it's really interesting what what we do there, and really in the forefront of kind of of medicine, Dr. Khyati Patel 02:40 and we really can't wait to talk to you about you know, what you do in detail later on. But just to remind our listeners, you know, we covered the Naloxone therapy and the pharmacist. You know, the role the pharmacists play in Episode 50. That sounds while ago and somewhat relevant. We also covered the CDC opioid prescribing guidelines in Episode 61 I remind you there is another version of opioid prescribing guideline that just came out recently. And so, long story short, this was a listener suggested topic. And so if that listener is still listening, thank you for the suggestion. Sorry. It took us a little bit long, but we brought the very best Dr. Dumais with us, so we were excited to get into the discussion. Dr. Sean Kane 03:22 So, Dr. Dume, you mentioned already, oud is opioid use disorder. I'm assuming this is kind of a diagnostic criteria from probably one of the DSM five or four or whatever number we're on right now. Maybe you could just kind of give us a sense of what goes into the diagnosis of opioid use disorder or oud, yeah. Speaker 1 03:44 So there's definitely, like all mental health conditions, substance use disorders, included. There's a list of criteria that we like to include to identify if somebody has, in this case, opioid use disorder. And in general, this is very similar across other substances, and the diagnostic criteria just changes based on that substance. So in this case, we're talking about opioids, but it could be cocaine, could be cannabis, other stimulants as well. So just some to highlight some of the most important ones is taking, in this case, an opioid in a larger quantity for a longer period of time than you initially intended. As we can see, what's been going on with our opioid crisis in the United States, a lot of patients were started on short term opioid therapy, and then they continue taking it long past when they didn't need that medication anymore. So in this case, like starting it like as a prescription that was given to them by their provider, some other things that I like to highlight when it comes to opioid use disorder is like spending so much time out of your day and impacting your daily living in order to obtain the substance, in this case, an opioid. So you are leaving work early or skipping work, or there is like. Like interpersonal stressors with people in your life, a spouse, a significant other, family obligations at home or work that you know you're trying to seek out the substance that you are now taking, and other things also to keep in mind too is potentially knowing that it's harmful and still using the substance, and then also, you know, just the symptoms of withdrawal and tolerance. So if you're taking it, what you were once taking before, and then you need a higher, higher dose to get the same effect, seeking out like a euphoric feeling from it, and then potentially withdrawal as well. So those are just some of them, but there is definitely an exhaustive list of this in the DSM five criteria. Dr. Sean Kane 05:43 And then, of course, like many of the DSM five criteria, there's kind of a laundry list you kind of add up and say, Well, you have three of the five criteria, or something like that. In this case, there are 11 criteria, and a patient needs to meet two of the 11 to have opioid use disorder. And then we can further, kind of discriminate based on mild, moderate or severe. Obviously, the more severe you're going to have more of the 11 potential criteria, right, correct. Dr. Khyati Patel 06:12 And so when you refer to these treatment options, Dr. Dumais, you know the the current recommendation for the treatment of oud is to use FDA approved treatments, and we will talk one by one, but in general, there are your buprenorphine, methadone or naltrexone, and the recommendation is that these treatments be provided by either a treating clinician. If they are not well versed in this therapy, they should be referred to a substance use disorder treatment specialist or something we call certified opioid treatment programs, the OTPs. Dr. Sean Kane 06:47 Why don't we start with the first of the three agents, buprenorphine. So this is a partial view opioid receptor agonist. So when we talk about a partial agonist, it means that it hits the receptor. It activates receptor, but because it's a partial activator, it doesn't do as good of a job as a full agonist. So most of our opioids are full agonists. Why is that of benefit with buprenorphine, that it's a partial agonist, where it's not activating the receptor, as well as some of these other opioids? Yeah. Speaker 1 07:18 So this is an interesting concept, and I know for learners or students, when they're learning about receptor activity, especially when it comes to partial agonists with buprenorphine, it's a little bit of a difficult concept to grasp, but it goes back to the HPA access and that dopamine release. So when you have full agonist activity, like a full opioid, you get that sudden like Rush and release of dopamine by having a partial agonist, it kind of allows for the release of dopamine to not be all at once, and it theoretically is supposed to break that reward pathway cycle and hopefully allow for that person to have used other behavioral techniques for their recovery, etc, and not have withdrawals and cravings over time. There's also this idea that a partial agonist like buprenorphine has what's called a sealing effect, so it's harder for them to have euphoria or get a high from buprenorphine as it is from like other full agonist opioids, and potentially not as easy to overdose with buprenorphine as we know is, you know, a reason why people there's an epidemic and crisis with full agonist due to the opioid related emergency and overdose? Dr. Khyati Patel 08:35 Well, that's pretty neat to know as to how exactly it works. There is currently quite a few different formulations available that are used for opioid use disorders. We have the ER subcutaneous injection, Brixadi or the sublocade. We have the sublingual tablets. We have generic version of those available too. And then, you know, not used for oud, however, transdermal patches are available. Mainly, these are used for pain treatment. So Dr. Dume, you know, you mentioned earlier that pharmacists like you at certain facilities are involved in suboxone induction. Can you kind of summarize as to what is a normal process of starting a patient on Suboxone just kind of like a generalized approach to dosing. Speaker 1 09:23 So as a generalized approach to dosing, it's really related to understanding what morphine milligram equivalents the patient was taking prior and the type of opioid that they were taking. Typically what we like to ask them, depending on the opioid they were on before. We like to say, you know, if they were on a longer acting opioid, we asked them to have taken their last dose at least 12 hours before, sometimes eight hours if it's a shorter acting opioid. And then we perform what's called a cows or like a clinical opioid withdrawal scale. And. In identifying how, what type of withdrawal they are in, if they're hopefully, we'd like to see them in moderate withdrawal, so slightly uncomfortable. And typically, we'll start doses anywhere from two to four milligrams. And then we'll repeat that scale, that withdrawal scale, and then potentially can adjust their daily dose for that day. Most patients who have opioid use disorder, and we're on pretty high doses of opioids prior to will be anywhere from 16 to 32 milligrams per day. But it really depends, again, on the patient and on the formulation that they're using. But when it comes to like oral Suboxone, I think most patients are at 16, and that's the FDA kind of like approved dose, but some patients have seen or have taken higher doses. Dr. Sean Kane 10:48 So Dr. Dume, we talked a little bit about dosage forms, and one of the dosage forms that I actually was not familiar with is that there's an extended release subcutaneous injection. Could you tell us a little bit more about what that is and what we need to know about it as clinicians. Yeah, this Speaker 1 11:04 is a really interesting kind of like, novel route of administration, and something that my facility utilizes quite frequently. What happens is that it's it is administered in clinic by skilled nursing staff, and if a patient has shown that they tolerate Suboxone or buprenorphine, they can become a candidate for sublocade injections once a month. Typically, the starting dose is a 300 milligrams. They take that for the first two months, and then, depending on the patient, they there, may go down to a maintenance dose of 100 milligrams. But even in some cases, other patients will stay on the 300 milligrams per month. What happens is that once it's injected in the subcutaneous layer within the under the skin, it creates this, like depot, kind of lump, and then throughout the month, it slowly releases buprenorphine into the body. This is also something that, if a patient needs, requires emergency surgery and needs, you know, pain management, that it can be surgically removed as well. So it's, it's, it's an interesting it's a great option for people who don't want to take something orally every day. Dr. Khyati Patel 12:16 And I can imagine it's also good for patients we're safe keeping, you know, sublingual tablets or those films are an are not an option, and so having them come to the clinic and having that administer, it kind of does, you know, two things it may, you know, takes the worry off of how to store the medication properly, but also improves adherence. Because they're coming to the clinic, they're getting the doses Exactly. Speaker 1 12:42 And also any stigma related to it, if there's an, you know, if they keep it around and somebody may see it, you know, there's always questions about it. This is something where, you know, it's, like, it's, it's, it's very kind of discreet, I guess, I would say. Dr. Sean Kane 12:56 And also, from a formulation standpoint, I feel like we should talk about the transmucosal, or sublingual tab tablets and films. So the sublingual tablets, we kind of already covered that, but the film is interesting because it's co formulated with naloxone. And at face value, you might wonder, why would you give an opioid antagonist with a partial agonist and Suboxone? Maybe you can kind of talk a little bit about why buprenorphine would ever be co formulated with naloxone. Speaker 1 13:28 Yeah, the CO formulation of this film combination product is, I think it's very interesting from from a perspective, because Naloxone has very little to no oral bioavailability. So when a patient is instructed to use the sublingual films appropriately dissolving it under the tongue, naloxone is basically not working. It's, you know, it's not bioavailable, so they're just getting the buprenorphine effects to help with the cravings, etc. It's used. The Naloxone component comes into play if the patient tries to divert the route of which they're using the sublingual film, so let's say injecting it, snorting it, anything else that isn't an oral route, that's when Naloxone suddenly, kind of like comes into action and then displaces all the buprenorphine, and they get essentially only antagonism from the naloxone. No buprenorphine is binding, and therefore there is no high or euphoria from this. So again, more for like diversion prevention, Dr. Khyati Patel 14:35 just briefly covering how effective is buprenorphine in order to treat oud, what is? What is the evidence so far Speaker 1 14:46 so looking at a meta analysis that included patients who were taking a total of 16 milligrams or more daily dose, the results showed that patients were almost twice as likely to stay on treatment as those who weren't, and there was almost a 15% reduction in the number of opioid positive drug screenings for those patients. Dr. Khyati Patel 15:11 And I think one thing that I came across, obviously, I don't practice in a setting where I see these patients, but one thing I came across, and literature was really specific and making sure that we are using effective doses of buprenorphine, because when the lower doses were compared, the efficacy was not there. And so as you mentioned, you know for for most patient on sublingual tablets, that 16 milligram maintenance dose is what we opt for. That's the dose we want to maintain patients on, because that's the clinically effective dose compared to some of the lower doses. Speaker 1 15:46 And like I said earlier, it's, in some cases, it's up to 32 milligrams, even though, looking at like a drug monograph, they will say, you know, 60 milligrams as a max FDA approved dose. Clinically, we see much higher doses for when it comes to patients treating oud, especially depending on the complexity of their substance use, how long they've been using, the route of administration that they were using, all of that does come into play in finding that optimal maintenance dose. Dr. Sean Kane 16:16 So from a safety perspective, you know, buprenorphine does have several box warnings. Many of these are the same box warnings that you're going to see on all opioids, but things like accidental exposure or overdose is possible. You can become addicted to the medication, the risk of abuse and misuse. Side effects like respiratory depression that can be life threatening. A lot of box warnings, which also plays a role in the typical side effects that we also see, like sedation, constipation, nausea, vomiting, things like that. These are fairly common side effects. Are there any side effects or serious side effects that you think are worth mentioning that are unique to Suboxone, whether it's a formulation thing or something with its partial agonist effect. Speaker 1 17:02 Yeah, I think one that has been added on recently, in the last couple of years, is especially for the sublingual formulation. Is like tooth decay, tooth carries that's something that we have started to ask our patients about at follow ups, is, you know, is post marketing is what we've seen. So that's something that we like to ask our patients. And then when it comes to the sublocade injection, pain or itching at the injection site or swelling is also common or should be monitored for. Dr. Khyati Patel 17:39 And so I bet, when you know, pharmacists have a role in initiating this therapy. I'm sure there is a role in monitoring for these side effects, you know, not just the efficacy of the treatment, but also the safety of it. And there is lot to do here. You know, one thing that is important to also understand, as we kind of talked about, what's the FDA approved medications and who's, you know, cleared, quote, unquote, to prescribe them. There was a, there was a groundbreaking change that happened in terms of buprenorphine prescribing, and that was part of that Consolidated Appropriations Act, or the omnibus bill of 2023, can you allude to that? Now, how significant that is, and what change occurred, actually? Yeah. Speaker 1 18:21 So this was kind of groundbreaking in terms of access to care, access to treatment. Previously, providers needed to have a specific X waiver, which required additional training and a maximum number of patients that can be registered with them for obtaining suboxone for treatment for oud, we have gone away from this, and X waiver has has dissolved, so those who now have an active DEA license can prescribe medications like suboxone for the treatment of oud without needing this so it improves access to care. For example, in my in my setting, within the VA there are pharmacists who, depending on the state, they can obtain a DEA license and can potentially help treat oud as mid level practitioners, whereas before, they weren't able to as pharmacists weren't allowed to have that x waiver. So that's really great. And again, just improves access to care, destigmatizing and getting people the treatment that they need. Dr. Khyati Patel 19:27 Well, that's great. Going from a kind of relaxed criteria for prescribing medication, buprenorphine, we're kind of going to another agents like weighing to methadone, which has certain restrictions on who you know, who can prescribe and where patients can obtain this medication, which we will discuss in a little bit. But methadone is also one that has been used the longest for the treatment of oud, let's say 1947 this one over here is a full mu receptor agonist. So. The previous one was partial. This one's our full new receptor agonist. Dr. Sean Kane 20:06 Dr. Patel is kind of interesting because, you know, for patients that have an opioid use disorder, it is interesting that we're giving them an opioid that is a full agonist, just like morphine or hydrocodone, something like that. So Dr. Dumais, maybe can touch base with us in terms of what's the rationale to give a full opioid agonist to someone who has an opioid use disorder to treat their opioid use disorder. Yeah. Speaker 1 20:32 So this is interesting. Some people will say, Well, isn't this just a band aid or, you know, it's very interesting approach. But I think the key here, when it comes to methadone and its success up until now, and it's still, you know, FDA approved and it's still recommended for certain patients, is the way that it's administered through those opioid treatment programs, or OTPs, like Dr. Patel had mentioned earlier in the episode. So there's access to therapists, there's access to a psychiatrist to evaluate the person's cravings and resources, and going to these OTPs and obtaining a daily dose, usually for oud, it's just a once daily dose, as compared to maybe in pain management, and maybe dose multiple times a day. So that's kind of like the unique approach to methadone and why it still potentially works as a treatment for oud, even though it is a full agonist. Dr. Khyati Patel 21:29 And when it comes to utilizing methadone, there's different formulations available, but when we are treating a patient with oud, we're mainly doing it with oral formulation, particularly that oral solution or oral soluble tabs and patients are required to make visits to these clinics that are certified. Obviously, the initial dosing is going to depend on patients tolerance, their withdrawal symptoms, their other medical conditions underlying signs of adverse effects, such as, you know, hypercapnia, hypoxia, any palpitations or arrhythmias noted, etc. But that initial dose, based on whether a patient is opioid naive or opioid tolerant, can range anywhere between 2.5 to 30. And then when it comes to maintenance dosing. You know, we titrate the dose to basically prevent the patient's withdrawal, cravings, any kind of euphoric effect, basically all the unwanted effects of the opioid use disorder. And then we're going to do a slower approach for titrations, about 10 milligram increase every five days, sometimes even slower, and that's where that, you know, check in with the treatment program on a routine basis will come in handy, because, as you mentioned, Dr. Dumais, there will be a slew of, you know, providers that would be evaluating the patient and deciding whether patient needs more or less treatment based on the treatment's efficacy and safety, Speaker 1 23:02 exactly, yeah. So it's kind of like an interdisciplinary approach. It's not just the medication. There's all these other components playing into it as well. Dr. Khyati Patel 23:10 And then in in regards to some of the pharmacokinetic PK/PD issues with methadone, Dr. Dumais, what can you what can you inform our audience, yeah. Speaker 1 23:21 So methadone, when it comes to its kinetics, it's it has very kind of complex kinetics. So when it comes to, like treating in a pain pain setting, it's usually a specialist who will do methadone, because it can change its order of kinetics depending on the total daily dose. But typically its duration of action is pretty long 24 to 36 hours, it's it's highly protein bound, and it's metabolized by a slew of SIP enzymes. Sip three, a, four, 2d six, 2c 19, two c9, and 2b six as well. So it's interestingly enough, looking at also is their serum concentrations. May drop of methadone, but the pharmacologic effects can still be maintained, again, probably due to its wild, wacky kinetics depending on the total daily dose. So it's a it's a complex medication, and probably also why it's usually only prescribed through these OTP settings or specialists. Dr. Khyati Patel 24:20 Thank you for that. And you know, again, kind of looking at methadone efficacy in in general. And this was a Cochrane Review back in 2009 where it looked at methadone plus psychosocial treatment. As you said, this has to be more of an interprofessional, multi professional approach versus placebo plus those psychosocial treatment, they found that patients with methadone therapy, they found 33% less opioid positive test and the patients were almost four and a half times more likely to stay in the treatment. And then we're also seeing that, you know, it provides even benefits in the absence of regular counts. Link services that doesn't negate the need for those additional services that patients may benefit. But that's something interesting that came out of this conference review and and generally, from what I reviewed, the treatment duration is 12 months. And so looking at some of the long term outcomes, six months or or longer have yielded, yielded better outcomes compared to the shorter term therapies. Dr. Sean Kane 25:25 And then, from a side effect standpoint, again, we do see the typical side effects that you'd expect from an opioid agonist. So we see things like nausea, vomiting, constipation, and really, for anyone who's on especially high doses of long term opioids, we'll see things like hypogonadism, decreased libido, things like that. Terms of some of the unique things about methadone, we can see some cardiovascular issues that maybe we don't see as often with other opioids. So we can see some bradycardia, tachycardia, palpitations, arrhythmias, and some of that is going to be driven by its propensity to cause Qt prolongation, especially at higher doses. And then finally, we also have a ton of box warnings, just like many other opioids. But again, unique to methadone is a box warning for Qt prolongation, the need to administer it in a supervised fashion. Some of the SIP enzyme interactions use with other sedating medications can cause respiratory depression, then also the risk of medication error based on the concentration use. So one milligram per ml versus two of milligram per ml, there's a risk there, terms of medication error possibility and box warning is present for that as well. Dr. Khyati Patel 26:48 So, you know, once again, this was going to identify the need for proper monitoring for the medications where pharmacists might be involved. And Dr. Dumais, you kind of had alluded earlier, and we discussed that, you know this methadone is is not available for the treatment of oud at your regular treatment provider or at a pharmacy? Is that right? Speaker 1 27:13 Yeah, that is correct. So if you out there listeners are filling methadone prescriptions, they're most likely tablets at a at a local pharmacy, it is for pain management. It is not going to be for oud, based on what we said earlier, for one the formulation and the setting that it needs to be dispensed in Dr. Khyati Patel 27:33 very good well, switching gears from our either partial or full agonist for the treatment of oud, let's talk about an antagonist, naltrexone that is also FDA approved for the treatment, naltrexone, as we know it's the competitive opioid receptor antagonist, and the structure of Naltrexone is kind of Similar to our nalorphine or Naloxone, it has the very high mu receptor affinity, it's going to kick off the opioids from those mu receptors kind of competitively block them, and so you would have less euphoric and sedative effects. Speaker 1 28:15 And in addition to that, we're also satisfying the cravings that a patient may feel because we're still occupying those receptors, but in an antagonistic fashion, we're going back reviewing the pharmacology and stopping that reward pathway in the HPA axis, hopefully, kind of retraining the brain and the brain chemistry to not seek out or crave those opioids that they once were. Dr. Sean Kane 28:41 But Dr. Dume, I know that we have an injection formulation and also some oral tablets. What are some dosage formulation considerations with naltrexone? Speaker 1 28:50 Yeah, so when it comes to the treatment of oud, the im injection is the one that is FDA approved for oud. Oral tablets have an added indication for both oud and alcohol use disorder. But when it comes to oud, there's a the clinical data showed poor outcomes with the tablets. It was really that monthly im injection called Vivitrol that has is what we use clinically, and what is FDA approved. Dr. Khyati Patel 29:20 And so, as you mentioned, Dr. Dume, this is going to be a once a month, you know, 380 milligram injection given by a doctor's office. It's an IM so it's injected in gluteal muscle. I think one thing to consider with just using naltrexone, it's not for everybody, right? So a patient must go through a full detoxification before they can receive the first dose of naltrexone. Can you kind of allude like, how is that important? And you know, kind of plays a role in terms of getting patients in line for the treatment. Speaker 1 29:52 Naltrexone is not necessarily like first line for somebody who is in active withdrawal or who last used an opioid agonist. Just in the last 24 hours. In fact, the monograph says that there, the patient needs to be at least 10 to 14 days, or depending if it's long acting versus a short acting opioid, they need to be show that they've been opioid free for at least, like a week to two weeks. And in the case of somebody who is in an environment where they are prone to relapse. This may not be a feasible option for them, but in the case of if somebody is in an inpatient, let's say treatment program, in a controlled environment where they don't have access, they have long withdrawn from opioids, or have not had access to any opioids, this is a pretty good option for them, because it, you know, right away you can start the injection, and it has a slightly different approach. So if they failed the partial agonists in the past, or methadone, or is, it's just not a feasible option. This is a great option as well. I want to jump to Dr. Khyati Patel 30:55 the efficacy. And we kind of highlighted that, you know, don't use the oral formulation of naltrexone, use the im that's where the better, better data and efficacy are laid. Can you summarize what we have seen as far as how naltrexone helps patients with oud? Yeah. Speaker 1 31:12 So looking at some of the data when it comes to increased opioid abstinence, 90% of patients who are taking it confirmed that they had abstinence weeks compared to only 35% of patients who are on the placebo equivalent. So definitely you could see the the pharmacology, the mechanism, coming into play there. There's also higher treatment retention seen with with this formulation, as compared to placebo, 58% versus 42 again, coming in and seeing your provider, that this just shows that while placebo is pretty high, it's, you know, it's even better with naltrexone. But that's like a piece that I really like, and patients really like that routine of seeing their providers. So there's something to say to that as well. There's also decreased drug cravings and relapse as associated with the using naltrexone im injection, 0.8% versus 13% with placebo. So definitely a very viable option for many patients. It just depends on the setting that they're in. Dr. Sean Kane 32:14 From a safety standpoint, it does have a rems guide for dispensing. From a side effect standpoint, it's kind of, again, what you would expect. So some GI issues, like nausea, vomiting, diarrhea, low appetite, maybe some headache or arthralgias, myalgias, things like that. From a more severe standpoint, it's an injection. So any injection site reactions are something we think about, including allergic reactions. There's also a risk of depression. And then finally, kind of an interesting one, is the risk of overdose. After stopping naltrexone, if a patient is used to not using an opioid, and they're on naltrexone, they take an opioid, they don't get that, you know, euphoric effect that they're looking for, and they keep to trying to take more and more and more, they're going to be at a higher risk for coma or death or respiratory depression, and the longer they don't use for the more likely it is that they're going to be more and more sensitive if they ever relapse and start using again. Exactly the Speaker 1 33:13 patient becomes essentially opioid naive by being on a full antagonist for a certain amount of time, which is slightly different than being on methadone or buprenorphine, where there's still that partial agonist activity. So that's why this present this particular box warning is, is here, from Dr. Khyati Patel 33:32 what I understand, Dr. Dumais, is, you know, anybody? Any clinicians with prescribing authority can prescribe it. There is some expanded authority until the October 1, 2023 for some clinical nurse specialists, CRNA and certified nurse midwives, which I assume that it would go away after that, but you might be seeing prescriptions coming from any treatment provider here. I want to take some time and talk about, you know, we talked about individual agents and their efficacy when compared to placebo, but there is some evidence out there as to if there is any treatment that's better than the other, and just kind of like comparing the three with each other. And so we group our buprenorphine and methadone as opioid agonist versus our naltrexone as an antagonist. Most treatment provider kind of want to go with that opioid agonist over the antagonist, and the reason is because there is limited number of studies with the naltrexone. We talked about the ER injection, naltrexone once a month, having a little bit better efficacy, and we summarized that earlier, so that formulation is definitely better than the oral ones. We talked about oral has poor absorption and efficacy thereafter, and so if the treatment adherence is poor with our naltrexone, that means it's decreased effectiveness, and therefore the buprenorphine and methadone kind of tops over the naltrexone treatment. But I really highlight what you said, Dr. Dumais earlier, it's going to depend on the setting and the availability of the medication. Treatment providers, the patient geographically, where they're located, and what kind of access to care they Speaker 1 35:06 have, exactly, exactly. Dr. Khyati Patel 35:09 Is there a difference now that, if we kind of turn the tables a little bit and just look at the two opioid agonists, the buprenorphine and methadone, is there a difference in efficacy between the two. Speaker 1 35:21 So clinically, there was no difference between buprenorphine and methadone. Looking at a Cochrane review, there was no difference in opioid positive drug tests, or in this case, the patient population self reported use of heroin. When comparing buprenorphine to methadone, again, keeping in mind under dosing buprenorphine, for example, using six milligrams or less may potentially have less efficacy. So ensuring that patients are getting an adequate dose can clinically show some differences, but from overall perspective, they are equally efficacious. Something to keep in mind, however, is that buprenorphine has less barriers to its access and potentially less stigma, as we said earlier, methadone is you need to get it from an OTP. You may have to initially go daily to access and obtain your medication. Versus buprenorphine, you go to a clinic setting in a hospital or outpatient clinic setting, you can take home a week's worth, two weeks worth, and take it at home. So there's definitely pros and cons to each one of them, again, depending on the patient, just like we said before. Additionally, with methadone, there's also, you know, medical considerations, the risk for QTC prolongation, respiratory depression, and those SIP interactions, so in patients who may have a lot of other medications they're taking, or cardiac comorbidities, this may be something that deters them from using methadone over buprenorphine. Dr. Khyati Patel 36:55 And then slight subset of comparison was also done looking at that buprenorphine/naloxone, which is our sublingual film, versus the ER naltrexone, and they found that when people have that detox with the ER naltrexone, and then the actual treatment was started, and comparing that to the suboxone film, efficacy was very similar. However, we know that the ER Naltrexone is not really recommended in patients who have high risk of relapse. We need to make sure that they're coming in the clinic routinely to obtain that injection on one's monthly basis. Dr. Sean Kane 37:31 So Dr. Dumais, we've kind of alluded to that. You know, in some circumstances, it's going to be a patient specific decision in terms of which therapy to consider. You've also alluded to comorbidities and other patient specific factors. Maybe we could just highlight some of those common comorbidities or patient conditions that do play a role in terms of things that also need to be considered while we're considering the whole patient. Yeah. Speaker 1 37:56 So again, this is kind of a very patient specific approach, as as are most of our psychiatric conditions that we treat within mental health. So keeping in mind other psychiatric conditions or psychosocial interventions that the patient may need if they need to daily kind of touch base, touch points, for example, methadone may be a better option for them if the patient has other substance use disorders, for example, let's say alcohol use disorder, something like naltrexone may be the best option at that point, because there's really great data for use of naltrexone for both comorbid conditions, if the patient may have complex pain plus oud, this also adds a level of complexity, and something like naltrexone may not be a viable option for them, because there is no analgesic effect with a full antagonist, as compared to a partial agonist or full agonist, buprenorphine and methadone. But it also something to keep in mind, is special category of pregnancy. While, yes, it's not a comorbidity, it's still an important topic to discuss, because there are recommendations for this patient population who have oud. Methadone for the longest time has been kind of like tried and true, safest option for use of oud in pregnant women. But more recently, there's been data to support that buprenorphine monotherapy has become more popular and accessible as well. The reason why we don't recommend suboxone buprenorphine with naloxone is that we don't have long term data on Naloxone exposure to the fetus as compared to buprenorphine alone at this time. However, with any kind of pregnancy related consideration, it should be patient centered decision making, risk versus benefits with the combo product, if that's something that maybe the patient may benefit from, as compared to buprenorphine monotherapy. Dr. Khyati Patel 39:53 You know you mentioned earlier, Dr. Dumais that your facility pharmacists are involved in suboxone therapy. So like they're working at the suboxone induction clinics, they're also offering various dosing techniques for the patients. Can you tell what other ways pharmacists can play a role in helping a patient when they have oud, yeah. Speaker 1 40:17 So while you know some of these may require some specialization training or pursuing a residency or working in specialized clinic settings. I do feel like a lot of what we can do as pharmacists with oud can be widespread regardless of area that you're in or specialty, and a lot of them is just education and just our own education around what treatment options are in your area, referrals to treatment centers in the community, understanding where there's a methadone clinic in your area, or access to any sort of oud treatment if they want to do something like Suboxone. As far as you know, education, we as pharmacists, and depending on what your state allows in legislation, dispensing Naloxone, prescribing Naloxone, and education on opioid overdose and how Naloxone can play a life saving role. That's something that we, anybody can do as a pharmacist in any setting, and as well with that, is just monitoring prescription opioid use, utilizing the PDMP with your state, and offering other non opioid pain management options for our patients, and educating on the risk with long term opioid use and storage and safe disposal, and you know, the list goes on in terms of like the interventions that we can make as pharmacists beyond, you know, like The treatment of oud itself, I think, is very impactful. Dr. Khyati Patel 41:43 Well, that was a fantastic overview, Dr. Dumais, of what pharmacists can do, you know, Dr. Kane, and I don't practice in that setting at all, so it's great to have your insight on, you know, even even a non specialized pharmacist, you know, how can they intervene and help curb this epidemic that we are dealing with. To kind of summarize the episode and the key concept, you know, we know that the treatment for oud should be provided by either the treating clinician, or they should be referred to a substance use disorder specialist, or even in the case of methadone, they're going to be have to refer to opioid treatment provider, and we're going to use the opioid approved therapy, which include the buprenorphine, methadone and naltrexone. Dr. Sean Kane 42:27 In terms of selection, you know, it's going to depend on the availability of the treatment provider, and then specific factors related to the the therapy. So effectiveness, dose titration, the safety of the medication. Case of naltrexone, the patient needs to completely detox for a week or two ahead of time, then patient factors like the ability to keep the meds safe and how adhered they can be to clinic visits other comorbidities or other conditions that they may have. So clearly, there's a lot that goes into the decision making process of which therapy to give a patient with an opioid use disorder. Speaker 1 43:02 And finally, you know, pharmacists can play such an important role for patients needing treatment for oud, which includes education, you know, treatment induction, monitoring those treatment outcomes, other harm reduction strategies, like providing Naloxone and education around overdose and utilizing preventative strategies, like using the PDMP, offering non opioid pain management strategies and promoting safe storage and disposal, as Dr. Kane mentioned earlier, perfect. Dr. Sean Kane 43:33 Well. Dr. Dumais, thank you so much for your expertise and time in today's episode, we really appreciate it. Speaker 1 43:39 Thank you so much again for having me on, I love chatting with you guys. It's been a pleasure, wonderful. Dr. Sean Kane 43:44 So for the audience, we do have some show notes available at HelixTalk.com we're also on Twitter at HelixTalk, and we have a mailing list. So if you want to get an email whenever new episodes come out with some Show Notes and references, you can sign up at our website, HelixTalk.com so with that, I'm Doctor Kane and Dr. Khyati Patel 44:00 I'm Dr. Patel, and thank you again, Dr. Dumais, for being with us today and to our audience, study hard. Narrator - Dr. Abel 44:07 If you enjoyed the show, please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review Narrator - ? 44:17 there to suggest an episode or contact us or online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.