Synthetic Opioids: Navigating a Changing Landscape in the Treatment of Opioid Use Disorder
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Welcome to this module today we're going to be talking about how to take care of patients with opioid use disorder who are using synthetic opioids my name is Jade Malcho and I'm a board certified emergency medicine and addiction medicine physician at UR Medicine Today we're going to discuss the evolution of the opioid overdose crisis we're going to discuss different synthetic opioids and discuss treatment approaches for patients who are using synthetic opioids be define find barriers to treatment in rural communities and how to address them I have no disclosures The overdose crisis began several decades ago and has come in several waves wave one is associated with the prescribing and over prescribing of of opioid pain medications pain prescribing practices were very liberal when pharmaceutical companies had many different kickback and referral programs and were over prescribing opioid pain medications and were advertising them as being non-addictive the initial wave of opioid overdose deaths is outlined in the light blue dots as the first wave which is the initial crisis of prescription opioids a few decades later we see the second wave of heroin-related overdose deaths around 2010.
This is associated in the use of heroin also known as mono-acetyl morphine A few years later in the early 20 teens we began seeing overdose deaths related to synthetic opioids mainly in the form of fentanyl where we see a rapid uptick of synthetic opioid driven deaths in the form of fentanyl also known as the third wave As depicted on these Maps there was a dramatic increase in almost all of the states year over year between 2018 and 2020 with increases in opioid overdose deaths by at least 50 percent we look at the impact to rural communities there are some patterns that I'd like to point out in 2020 if we look at the rates of overdose deaths there are some patterns geographically that are depicted on this map so nationally the the rates nationally are are pretty similar if we look at urban and rural counties across the U.S
although if we follow the Appalachian region which is between the Southern Tier of New York following down northern Mississippi and West Virginia kind of across this 13 State band the overdose death rates related to synthetic opioids were dramatically higher up to three to four times higher than national averages the highest being in West Virginia up to 65 deaths per 100 000. per capita which is three to four times higher than national average and so the impact to some rural communities for synthetic opioids is really important when we start thinking about how we approach the treatment and approach screening and our response to synthetic opioids in these communities in the category of synthetic opioids this would include fentanyl fentanyl analogs such as alfentanil, remifentanil, sufentanyl and then you have novel synthetic opioids there's a list here which include a lot of letters and numbers and there's constantly new ones being generated by definition these are all synthetic therefore they are not naturally occurring made in labs and they're different they're because of this they're difficult to detect in the urine drug screen because they're all slightly different in chemical structure than each other today we'll be discussing mostly fentanyl as it's most common and it's counterpart illicitly manufactured fentanyl and a common derivative carfentanil chemically there is no difference between pharmaceutical and illicitly manufactured fentanyl if you were to look at them under the microscope they are both fentanyl in chemical structure pharmaceutical fentanyl although we know what we're getting it's made in a predictable way under the eyes of the FDA in an approved lab it's prescribed by a pharmacist as a transdermal patch, pills, or lozenge as a predictable effect and a concentration although it can be diverted for misuse in the U.S. on the other hand illicitly manufactured fentanyl it's made or manufactured in unreliable basements or labs if you call them that might come in a liquid or a powdered form or a pressed pill they're certainly unreliable estimates of concentration or what they're cut with or what they're mixed with it might appear identical to pharmaceutical fentanyl might even look like a pill of Oxycodone the pictures on this slide hold true for both pharmaceutical and illicitly manufactured fentanyl and it goes to show the concept that you need fentanyl is very potent you need very little fentanyl because it is so strong compared to the same amount of kind of weight of heroin that you would need to achieve the same effect so small errors in measurement and dosing can really make the difference between life or death there are many cases of fentanyl and illicitly manufactured fentanyl being mixed with other drugs it can be mixed in different ratios so that's what this kind of chocolate chip cookie effect is showing us where a portion of a drug may contain a small or a large portion or none at all of fentanyl and you don't really know what you're getting there's a list of reports of it being mixed with heroin or cocaine methamphetamine counterfeit pharmaceutical pills also known as kind of pressed pills there are mixed reports anecdotal reports of it being mixed with marijuana although no real kind of evidence or research to support this but it has been reported by law enforcement agencies it's really important to keep in mind that as providers thinking about opioid overdoses and patients who don't only have opioid use disorder right patients who have stimulant use disorder might need to be we might need to be thinking about how do we take care of patients who have other substance use disorders are at risk for opioid overdose in this synthetic opioid epidemic this brings about the concept of what is the role for testing for fentanyl there are now fentanyl test strips which are a type of low-cost harm reduction strategy to prevent opioid overdose these fentanyl test strips can be used to test different forms of drugs or formulations of powders pills or injectables before a person who uses drugs makes a decision if they want to use that particular drug you only use a small amount you mix it with water you dip your test strip in you follow the specific indicator lines to guide you if it's positive or negative or fentanyl when educating a patient about fentanyl overdoses it's important that they know a fentanyl overdose or any opioid overdose can occur when they inhale inject or ingest an opioid in its various forms although the overdose cannot occur through simply touching of the fentanyl powder and that the standard medication to reverse fentanyl overdose is naloxone also known as Narcan one synthetic opioid analog to fentanyl is carfentanil it is 10,000 times more potent than morphine and 100 times more potent than fentanyl we have seen it come up in hot spots in the U.S. and because it has a much higher potency than fentanyl it often presents as requiring many more doses of Narcan to try and support a patient's respiratory effort the overdose death potential is much higher than that for fentanyl or heroin as the illustrations on this slide depict because of its potency a dose of what would seem to be a small amount 2 milligrams could knock out an average size elephant it was previously FDA approved in large animal anesthesia and that same amount is enough to kill 50 people so this certainly posed a huge public health risk it is a catastrophic event when carfentanil and other very potent synthetic analogs find its way into the general population if you compare the amount of that two milligrams the amount to take out an elephant is compared to a penny it's exceedingly small and can can be incredibly catastrophic and when an overdose like this makes its way into the emergency department it can wipe out an entire Narcan supply for one patient as we continue to talk about the approach of how we treat and manage opioid use disorder in the era of synthetic opioids the problem has been compounded by the recent impact of a non-opioid sedative known as xylazine in 2022 an increasing in relevance and prevalence into 2023 this non-opioid sedative which also functions as an analgesic and muscle relaxant in the veterinary medicine world is never been approved for human use but in the past several years it's been found mixed with other drugs like heroin methamphetamine cocaine and fentanyl it has been described by persons who use drugs that it gives opioids legs which means that it extends the duration of the effect of the opioid or the drug in the person who uses the drug and so it is usually a desired effect but isn't always something that is sought out by the user and it's sometimes something that is incidentally found in the drug because it is in the drug supply that people are buying unfortunately it has many negative consequences we're going to talk about both the skin ulcerations that are a telltale sign of its use as well as the compounded increase overdose risk skin ulcerations are something that need to be educated for our patients that are injecting xylazine because the necrosis is severe and when it occurs requires immediate treatment to avoid severe infection chronic wound scarring and these infections can lead to significant morbidity mortality and death the death risk although we are still learning depending on how much xylazine is in the mix which that varies and similar to what we talked about before with how much fentanyl is mixed in to what the person who uses drugs is consuming because that is variable depending on the dose and the quantity the amount of respiratory depression effect that xylazine might contribute compared to the amount of respiratory depression depression effect that the opioid might contribute is a balance and it's unpredictable but xylazine does contribute an overdose risk when respiratory depression effect does happen an altered mental status respiratory depression does occur naloxone does not reverse the effects of the xylazine in and of itself naloxone is still recommended to reverse the opioid effect from the likely fentanyl that was consumed with the xylazine and it will help partially unmask that portion of the overdose but the xylazine respiratory depression effect will still persist so it's really important that it is understood that there's only so much we can do to protect our patients from xylazine also known as tranq and the risk that comes from that the DEA has been reporting kind of the incident that they're finding xylazine in different forms of fentanyl as you can see listed here and as well as the increase in amount of fentanyl deaths where we are detecting xylazine and it's really also hard to actually find linearize the causality of this like is it xylazine that's causing the five-fold increase in deaths or is it the fentanyl but there is an association here and so a lot more studies need to be done to figure out what is causing the increase in these deaths but it can't be ignored that we are seeing xylazine as a factor so what can be done for now so educate patients that the amount of xylazine might vary there likely is an increased risk that contamination xylazine in the drug Supply will increase your risk of overdose naloxone is not a panacea cure-all for reversing overdose of xylazine and that we can't screen for it routinely at least at least not now harm reduction recommendations don't use alone stagger use with others so that way someone is alert and available to respond in case of emergency point of care testing xylazine test strips similar to the fentanyl test strip that I described earlier we're still learning about kind of levels of detection and clinical relevance and still administer naloxone to to kind of reverse the opioid effect if they are present and call 911.
your patients options for medications for opioid use disorder remain the same when they are using synthetic opioids the gold standard for the CDC remains methadone which is a full agonist and there are other model modules on the RCOE website if you'd like to look further into the different mechanisms of action for these MOUD treatment options when thinking about how you would start methadone for someone on a synthetic opioid it would be no different but we will go into different considerations of how to initiate buprenorphine for a patient who's using synthetic opioids when considering
naltrexone it is still important to have a appropriately long washout period of at least 14 days if not longer for avoidance of precipitated withdrawal and I will say an experience for those using synthetic opioids it would be incredibly challenging to do that safely without risk for relapse and return to use unless you are in a very controlled setting such as an inpatient setting either in the hospital or in an inpatient treatment facility to do that without interruption if you and your patient have decided that buprenorphine is a good fit for them the next step is deciding how we are going
to try to transition a patient from using fentanyl and starting and continuing buprenorphine in order to think about the difference of how we start or initiate buprenorphine in the era of synthetic opioids I like to compare it to the difference between starting buprenorphine in someone who is taking a short versus a long-acting opioid in the traditional sense when we do a standard induction for someone who was on oxycodone or traditional heroin mono-acetyl morphine that was a short acting opioid and the traditional method was a standard quote-unquote standard washout which usually we waited
for them to go into moderate withdrawal usually within 8 or 12 hours and once that happened gave them a small dose of two milligrams and followed that up with eight milligrams and you were good to go on your way stop the heroin start the start the buprenorphine with fentanyl it's a little trickier because fentanyl doesn't wash out of the system the same way that oxycodone or heroin did it actually sticks around a bit longer similar to a longer acting opioid like methadone and it does this because it's lipophilic it has a protracted renal excretion and it requires a longer washout period which
is challenging for patients to tolerate this period of abstinence and it increases the risk of precipitated withdrawal if we start too much buprenorphine too fast or too much too soon and so there's there's several different proposed induction methods but there's many different variations of how to do this in different settings depending on if your your patient is at home some protocols occur over a few days some protocols call for patients to continue the use of their opioid during this process which can allow them to slowly taper off which is shown by this graph they slowly taper off their
opioid use while slowly increasing their buprenorphine which allows them to not have to go through this really uncomfortable withdrawal period which can be a barrier to starting buprenorphine treatment because some patients find that very fearful they and will say I'm not going to start bup because I can't go through that transition period fentanyl synthetic opioids have made it too hard and because methadone would be the only other medication that would work for for me and in my rural setting it's too hard to get to I don't have a treatment program near me I don't have any other option well
this could be your option this is a good tool to have in your toolbox so these protocols are changing there's methods are evolving and we have multiple protocols that are updated as they come out and if you check the website at UR Medicine Recovery Center of Excellence we'll have the most updated version protocol there for you so like I mentioned when we think about the different types of medication for opioid use disorder options I mean this all goes into a patient's decisions and a provider's decisions of what they can offer because depending on their location and rural barriers to
accessing certain types of treatments and certain levels of care this might change what treatments are available to them and what their choices are so I mean there are a number of barriers to rural residents for accessing what would be the recommended treatment that's available to them in their communities I mean 80 of rural areas have no medically assisted withdrawal also known as detox services I mean these detoxification services are one of the ways that we get patients on to all forms of medication for opioid use disorder treatments and can be one of the only pathways to get patients into
an inpatient treatment facility or into stabilized housing 80 percent of treatment facilities are located in urban areas I mean this is a huge gap and so if the majority of treatment options for patients who live in rural areas are all in the outpatient setting when patients have failed outpatient treatment options and they've required higher level of cares it's not where they live and and they are kind of forced to stay in the outpatient setting and they have to drive so far to get to their outpatient treatment so there's transportation distance barriers they can't even get to the level of
care that they require so it's a gap in our system for equity when we talk about access to buprenorphine treatment I mean we're talking about the difference of 15 to 20 minutes when we talk about access to methadone we're talking about almost an hour difference so when a patient's deciding between the treatment options right so do I go on bup which is harder to get on in the era of synthetic opioids maybe I haven't been able to get on it in the past I struggle with precipitated withdrawal but it's easier for me to navigate because my doctor prescribes it I only have to drive 20 minutes I only
have to go once a week but methadone might work better for me and I can get on it but I have to I have to drive an hour every day I have to go to a methadone program every day but because I live in a rural community it's different for them so not only I mean we talked about the overdose death rates are higher and accessing treatment is harder that the deck is stacked against our our patients in rural communities so what can we do so yes increasing rural access to MOUD is happening we can make that happen the removal of the X-waivers already happened so it happened at a federal level in 2023
thankfully this piece of legislature no longer requires any extra training to prescribe buprenorphine for opioid use disorder any person who has a DEA registration prescribed buprenorphine for both opioid use disorder and pain so PCPs everywhere including in the rural setting regardless of any additional training they can prescribe bup what else can we do to increase rural access to medication for opioid use disorder so partnering with substance use disorder treatment clinics so if if we can create relationships for PCPs to manage medications who require long-term buprenorphine treatment and
kind of to allow transitions of care to happen right so if a patient starts at a substance use treatment clinic and is doing well doesn't require that extra level of care or support can move to a primary care doctor who can continue their buprenorphine without need for that X-waiver or extra regulation and then if they aren't doing well there's a relationship open kind of door policy communication and they could feed back into the substance use treatment clinic system if there's ever any need and so the resources go and it can be kind of a if the higher level of resources are needed that can
happen at the substance use treatment clinic and the stable patients can stay at the primary care doctor level and so everyone kind of helps each other out and neither program feels overwhelmed and all patients can kind of get the care that they need providing access to and starting medication for opioid use disorders is just one way that you can decrease the risk for opioid overdose for patients who have opioid use disorder here are listed multiple risk factors for opioid overdose and the second one is where when a patient has an opioid use disorder and they are not MOUD is a risk factor for
overdose misusing prescription opioids or using heroin and then synthetic opioids is certainly a risk factor having a history of an opioid overdose is another one and being released from incarceration with the history of opioid use disorder articularly when they're not on medication for opioid use disorder these patients are at very high risk for opioid overdose trying to figure out and balance how do we screen for these very high risk factors is Incorporated in many other modules in the RCOE SBIRT talks and can be found on the website as we begin to wrap up this presentation I would like to
leave you with a few relevant strategies to try to prevent opioid overdose deaths being able to encourage people who are at high risk as well as their family members providers and other community partners to learn how to prevent and manage opioid overdose being a part of the solution of building up our community's access to treatment including decreasing the barriers to both medication for opioid use disorder in all communities particularly rural communities as well as the different levels of care for substance use disorder treatment for individuals who are misusing opioids and to have other
substance use disorders ensuring ready and available access to naloxone encouraging the public to call 9-1-1 and avoiding stigma around this and encouraging prescribers to using state prescription drug monitoring programs these are all things that we can do that can in cumulative effect help save many lives here are links and helpful resources for contact information for UR Medicine's Recovery Center of Excellence and I appreciate you listening thank you for participating today and please reach out to us with any questions
Jade Malcho, MD, FASAM
This 35-minute module focuses on how primary care providers can navigate the changing landscape of opioid use disorder in relation to synthetic opioids. The module discusses synthetic overdose in relation to fentanyl and fentanyl analogs, as well as the dangers of xylazine. It provides treatment recommendations for patients who use synthetic opioids and overdose prevention strategies.