31. Naloxone and IV Drug Use

(upbeat music) - This is Addiction Medicine Journal Club. I'm Dr. Sonia Del Tredici. - And I'm Dr. John Keenan. - We believe that addiction is a disease that can be treated and we wanna help you stay up to date with the latest research that you can use in your addiction medicine practice. This week we're gonna be discussing an article about changes in IV drug use after meloxone training. So how are you tonight, John? - I'm tired after a week of inpatient medicine, but I'm ready to go and excited to talk about some addiction medicines tonight. - Excellent, me too. So, John, what have you been thinking about in addiction medicine this week? - You know, one thing, it's not really kind of news, but it's something that comes up from time to time when my partners or other docs reach out to me, or actually even a very close friend recently about kind of gambling disorder. And what can you do about this? And I'm not sure many of our listeners probably are aware, but the majority of states, and I believe almost all of them at this point that have legalized gambling, there's what's called a gambling self-exclusion program. And it's often regulated by the gaming board of each individual state. And people that have a gambling issue or they have problems with gambling, you can self-register for this program. Often time for a fixated amount of time, I can tell you like the state that we live in, it's 12 months is the minimum, but you can do it in increments of one, two, five, or lifetime registration. And once you're registered on it, basically what they say is, quote, you can collect winnings, recover losses, or accept gifts or services from any location that is kind of providing gambling services. So essentially, it takes away the thrill of gambling, but also kind of a lot of the concern regarding the losses with gambling. And I think many people have come to me, we've talked about this for casinos, which I think are what most people think of. But I was surprised the other day, when I went to the website for our local state, which is Pennsylvania, and that not only is it casinos, but it's now kind of been expanded to reflect the new gambling trend. So it includes interactive and online gambling, video game terminals, and actually fantasy contests are also now one of the four categories where you can self-register and exclude. So I think that's a great resource for anyone that has a gambling issue or knows someone that they love has a gambling issue. Have you ever referred a patient to that? - No, I haven't. I've heard about them before, and I think it's really cool because I don't know, just gambling can be really, really hard, and I know a lot of people have trouble stopping it. So if you can, when you're feeling strong, you can self-exclude, and then in moments when you're feeling weak, you can, you're already excluded. You don't have to try to make that decision over and over again. I think that's really awesome. And I'm super glad that online gambling is included, because I imagine that's even worse than casino gambling, because you could do it anywhere like from your phone in your pocket, at your home. There's such a low barrier to doing online gambling. I'm really glad you can self-exclude from those sites as well. - Yeah, I think it's an interesting evolution to reflect kind of patterns of consumption of that voice, you know? - Do you know how many people self-exclude did any of your information have that on it? - You know, I don't have the number. That would be great information to know. I think the idea there's a resource there was kind of what I was trying to hint at, but probably I would guess it's underutilized. - Yeah, we'll figure it out. We'll give an update if we can find that number. - Yeah. - You should've done that before this talk. - That's okay. - How about you, Sonia? What's to do with you? - I didn't mean to gotcha on that fact. No, I wanted to share a report from the CDC that I read about that was about different rates of drug use by a profession. And they listed the top 10 professions with the highest rates of drug overdose deaths in the US. And it was just really interesting because it kind of matched what I see in my patients. We were talking about this earlier, so I won't quiz you on it 'cause you already know the answer. But the number one job for drug overdose deaths is fishermen. And we don't think about that where we are because we're landlocked here. So I don't think I have any patients who are fishermen, but I can imagine it 'cause it's a profession that's very physically demanding. I imagine there's a lot of injuries and pain. It's isolating, it's dangerous. Maybe kind of boring a lot of the time, a lot of kind of waiting around. So I can imagine that fishermen do use opioids. And then after that, it was sailors and semen, roofers, forest and conservation workers, drywall installers, restaurant servers. You can see there's a theme here. Painters and construction workers, maintenance workers, installation and repair guys, so sort of like buildings and grounds, stone masons, iron and steel workers. So I really do see people in those professions except for the fishermen in my OPEU's disorder clinic. Does that match what you see in your patients, John? - Yeah, I would say that kind of the majority of my patients are some sort of physical labor type job or kind of work at a restaurant. That seems to be the two themes. - Yeah. - And they're super nice. I always got, my wife was always surprised that I knew so many people at the restaurants when we go out for the limited times who do in our town. And off the time, they're very appreciative patients. Sometimes I've got some extra calamari. - Nice. - The one thing that I saw was missing from this list was the women, which I thought was interesting. These are all kind of male heavy professions, fishermen, roofers, lumberjacks, drywall and stallers, except for the restaurant servers. These are all pretty much male professions. And I don't know if that women, their work is not really considered a profession. They might be working more kind of on and off because of the demands of child rearing. Or I don't know, I just wonder why so many men have sort of a named profession well. So using opiates, but women, not so much. Why do you think? - I'm not sure. I mean, the only thing I would say is I actually think a lot of my people with substance use disorder, I'm actually thinking of a couple now. They actually kind of like gender a typical jobs or not like not the typical ones that you would stereotypically give to a female. Like I do have some that have construction jobs or warehouse jobs or factory jobs. That might be like in relation to where we live and kind of what jobs are available. But I wouldn't consider those kind of typically like quote female jobs, but a lot of them have them. And maybe that's maybe that's the reflection. Maybe it just is, they're just normal people like the other patients. - Yeah, I just thought it was, it was really interesting. There also of course makes me anxious. They're all jobs where you can really be injured if you're cognitively impaired. You know, I have a bunch of patients who are roofers and almost all of them experience major accidents, you know, like falling off the roof due to drug use on the job. You can only imagine, you know, fishermen and sailors, lumberjacks, people doing construction, who are doing it while impaired with opioids. It just at least injury. And then that is those injuries lead to chronic disability and pain, which exacerbates the problem of opioid use disorder. And then when they can no longer do those professions, they're a little bit at, you know, at sea about what to do next. So John, I'm excited to hear about this article. You know, I had heard about this on social media and I'm just really excited to hear your take on it because I have heard people say that distributing the lock zone just would encourage people to use more drugs. And I'm interested to see some data on that topic. - Yeah, so I think this is a really important article for kind of just actually general practice and not just addiction medicine. So it's basically the article is called Injection Drug Use Frequency before and after take home the lock zone training. And it's from JAMA Network Open from August 2023. So a little bit of background. In the lock zone as everyone here knows is a life-saving antidote to opioid overdose. Take home the lock zone training programs, abbreviated THN involve overdose response education and the lock zone supply were developed to increase the availability of the lock zone in the community among people who may be present in the event of an overdose. So targeting kind of bystanders present not necessarily the person kind of participating in illicit drug use. The distribution of take home the lock zone in the community has been associated with subsequent reductions in overdose death of the population level. The concept of risk compensation, which is something I've never heard of before, basically refers to greater risk taking due to an individual's perception that the risk associated with an activity is diminished with the implementation of public health interventions. And it's a major theoretical barrier to implementation of take home the lock zone programs. And you know, we're talking about the context of these lock zone programs, but the same idea kind of can be extrapolated to kind of helmets with motorcycles or other kind of risky activities that public health is coming and kind of mandated certain safety restrictions. - Well, and people have complained when mandatory seatbelt laws were enacted or mandatory helmet laws. People always complain that it's just gonna lead to more accidents because people will be driving or motorcycle in a more risky way because it's safer, but that hasn't really played out. I mean, there are some examples where that moral hazard does lead to more risky behavior. You know, if you make a behavior more safer or more comfortable, people will do more of it. But the examples aren't very common. Usually if something's really risky and you make it less risky, people don't do more of it. - A recent systemic review by Tess at all identified a small number of studies that examined change in heroin use as a marker of risky drug use after take home the locks and programs. There were five studies and they all observed an absence of compensatory risk behavior from heroin use measures in these patients. So kind of we have a little bit of background that this may not be a strong effect whatsoever. Intervenous drug use is associated with enhanced bioavailability and absorption of drugs as well as higher overdose risk. So we kind of also use a surrogate marker of risk as IV drug use as compared to oral or intranasal use. Say at all found no studies that formally analyzed changes and reported injection drug frequency while controlling for potential co-founding factors in people who inject drugs who had access to take home the locks and so really, we don't have a great adjusted study here. What's the clinical question of this trial? Do people who inject drugs increase their injection frequency after take home the locks and training and supply? A little bit about this study. So the study design is this is a longitudinal cohort study comparing risk behaviors and 189 active participants and the Melbourne injecting drug users cohort study also called the super mix study before and after take home the locks and training. So basically this is a subgroup from that trial. Just to give you a little background about the super mix cohort. This is a cohort of 1,328 participants who inject drugs that were recruited between 2008 to 2010 and then again in 2017 to present. Participants had annual follow up including in-depth face-to-face or telephone interviews gathering information regarding adverse health outcomes, cessation of and relapse patterns of drug use and impact on health service access. The only inclusion criteria to be part of the super mix cohort was you had to be a resident of Victoria, Australia. You had to be 18 years of age or older. You had to inject heroin or methamphetamine at least six times in the previous six months. You had to have a valid Medicare number and just let you know Medicare in Australia is their universal healthcare system. So pretty much a universal access to healthcare and no kind of discrimination by kind of private insurance. You were able to provide consent. So that's the cohort that the study was derived from. So 189 participants were derived from this 1,328 participant cohort. The exposure of interest was first taken in the lock zone training. Primary outcome was injection drug use frequency. So how many injections occurred in the seven days prior to interview? They looked at secondary outcomes including opioid injecting frequency, use of drugs alone and benzodiazepine use frequency, also kind of a surrogate of riskier opioid use. Statistical analysis was relatively complex as most of these are. It used these generalized linear multilevel modeling with covariant analysis. So trying to kind of sort out the actual effects of the take on the lock zone training. What did you think about the clinical trial and the questions on you? - I thought it was a great question and it made me think how this same question could apply to any kind of harm reduction initiatives. So take home the lock zone is something that makes drug use less risky. You know, people have the same concerns about syringe exchange or safe consumption site or safe supply or really anything that might make someone who uses drugs more comfortable unless at risk. That somehow that'll encourage people to use drugs. And what we've learned over the years is that making drug use unpleasant or risky has definitely not discouraged people from using drugs. So I think it's a great question to ask 'cause a lot of people who aren't in the addiction treatment community or who don't have a lot of experience with people who use drugs, it might seem like you're just making it easier for people to use drugs and won't that encourage more drug use. Even though to us it seems kind of obvious that giving out in a lock zone is not going to encourage drug use. I think it's a question that needs to be explicitly studied for, I don't know, just for the general population. - So is this trial valid? A little bit about the study. So the study was funded by the Colonial Foundation Trust and Grants from the National Health Medical Research Council. So kind of no industry funding here to kind of bias the authors. There's a longitudinal cohort study. So this was basically a subgroup of this cohort. It was non-blinded. It was not a randomized control trial. While the supermix cohort was a large sample size, you know, over 1,000 patients, statistical analysis and this subgroup was limited to 189 of those participants. So only 14.2% were actually included. Supermix study inclusion criteria of six episodes of injecting heroin or methamphetamine in the past six months. It's unclear. It could have been in the appendix somewhere, but it's unclear if actually you could be included as kind of a methamphetamine mono-user. So really not someone that would possibly benefit from Naloxone because you don't use opioids as well. That might have been a minority. I think most of the data shows that probably methamphetamine users also are opioid users for the most part. Outcome data regarding drug use was limited to frequency of injection and did not include data about potency or quantity. So that was kind of an author critique of their own trial. They thought that possibly you could still inject the same frequency, but with the use of Naloxone or Naloxone training, you would do larger quantities at a time. The author also felt that take-home Naloxone training may not directly reflect access to take-home Naloxone. So you can get Naloxone from multiple sources. So not necessarily just from kind of a training site. So a take-home Naloxone program involves not only distribution of the product, but also a class where you're trained on the use of the product. So I think there's open access in many other regards, some pharmacy programs, some safe distribution sites of Naloxone, and also take-home Naloxone training is really targeted to bystanders, not the person using drug. So basically freeing to use on someone else. So they thought that maybe that might skew this data just a little bit. Take-home Naloxone training is targeted to patients. Like, as I said in the last statement, it's targeted towards people that are present, not the patient themselves that's using. So maybe this was kind of not quite the surrogate marker they were looking for. And when they talk about this, this is a prospective cohort study. Participants who were included in the final sub sample may not reflect all participants who reported take-home Naloxone. So they thought that maybe the fact that the participants included here actually underwent that training, it might have like, sub-selected for possibly a a more risk-aversive drug user than someone that did into this training. Do you think those are fair? - Yeah, those are all fair critiques. And I think like a lot of studies of people who use drugs, it can be hard to, I don't know, have a super clear clinical question. You know, there's just so many confounding factors and you know, the patients do what they want to do so they don't necessarily, I don't know, it's just hard to do a clean study. So I think they did the best they could, but I think those are definitely fair critiques. - So a little bit about the results in the participants. So participants, like I said, there was 1,328 participants in the super mix cohort baseline, the majority were male, 67.2%, 32.5% were female. We look at who was excluded from analysis. So out of that 1,328, 363 did not participate in an interview after 2017, so they didn't have data on take-home naloxone training. 575 did not receive the take-home naloxone training. 188 had baseline take-home naloxone training, so there was no way they could distinguish a pre and a post in that group. Eight were lacking take-home naloxone training information for reported no drug use and one had missing data. So that's how they kind of dwindled it down from so many patients down to the 189. When you look at it, 14.2% of total super mix cohort were included in this statistical analysis, 189 patients, 183 out of 189 reported using opioids at baseline, so 96.8% reported baseline opioid use, 129 out of 189, 68.3% reported an opioid overdose in the previous 12 months, 170 out of 189 reported entering drug treatment programs in the previous 12 months, which was 89.9%. - Wait, what percent had an overdose in the previous 12 months? - 68.3% - That's kind of scary. - It's pretty high. So what are the results of the study? So the main outcome of interest, so when you look at kind of how much follow up they had, so the average participant had a mean of 6.2 interviews per participant. So and that has a standard deviation of 2.2 interviews. There was a total of 933 participant interview observations that were included in this trial. The primary outcome injection drug use frequency with regards to the pre and the post take home nooxone training, there was 10 with a standard deviation of 14.8 injection drug uses pre versus 12.9 with a standard deviation of 17.3 post take home nooxone training for the secondary outcomes. For opioid injection frequency, it was 7.5 versus 9.3 with a standard deviation of 10.5 and 14.1, so they overlap plates substantially pre and post. Use of drugs alone, basically you are injecting by yourself. 37.9% pre and 38.5% post with a standard deviation of 0.4 in both groups, pre and post take home nooxone training, benzodiazepine use frequency was 4.3 episodes of use with a standard deviation of 8.4, pre versus 3.8 with a standard deviation of 6.4 post take home nooxone training. So that's kind of like your data that they looked at before they went to the generalized linear modeling. So they basically did this generalized linear or multi-level modeling and since to be analysis to adjust for co-founders trying to find out whether or not co-founders alone could adjust for those differences between the two groups. Spoiler alert, there's no association here whatsoever. So there was a modest, non-statistically significant reduction in injection use frequency. So like they said that there is thoughts that possibly there could be a trend from this training to actually decreasing your drug use, not increasing. It was not statistically significant in this study at a P of 0.51, but it seems like there was a trend there. I just was gonna say I'm not surprised that there would be a decrease in injection drug use after a nooxone training as opposed to an increase because I think the nooxone training really does drive home the risk of opioid overdose and does scare some people. They make some think about overdose and it also seems like if you are doing something like an nooxone training, just in general, you're probably taking a little bit better care of yourself than people who aren't doing an nooxone training. So I can imagine that just going to the nooxone training, it's a sign that you are thinking about your life, you're taking care of yourself, maybe you're gonna reduce your drug use a little bit. - Yep, there was no association between take home the nooxone training and opioid injection frequency. There was no association between take home the nooxone training and opioid use alone. And there was no association that was statistically significant between take home the nooxone and benzodiazepine use frequency. So take home the nooxone training in this study, slight non statistically significant reduction in injection frequency, but no statistically significant association between the training and opioid injection frequency, use no opioids alone or using benzodiazepine. So really kind of no real change here. Does that surprise you? - Not really. I mean, I don't know what the culture is like in Australia, but I know in our area pretty much everybody knows about nooxone already. So I don't feel like going to a single nooxone training would necessarily be something that earth shattering for people. So I'm not surprised there wasn't a huge difference before and after in any direction. - So kind of summarizing will these results help me in patient care, a family medicine physician first, but I also specialize in addiction medicine. I manage patients on chronic opioids and treat patients with opioid use disorder because I care for these two vulnerable populations. On be honest, I prescribe a lot of the nooxone. I would say a lot and I'm actually always surprised with how much I prescribe it, how often it is used. I think a lot of people that aren't kind of routine the nooxone prescribers, I think if they were doing it more, they would be surprised to hear patients kind of tell how much this changed someone else's life or it was used on them by a family member. The thoughts really never crossed my mind that take home nooxone training could result in risk compensation behaviors and that it would actually risk the lives of my patients. I'm sure that some physicians and a population of non-clinical people do have that concern, but it's not just something that I've ever really kind of thought is a legitimate risk. - It's a great point, John. I have to say, when I prescribe nooxone as well, I always ask patients, I have like a little checklist and on it is, do you need nooxone? And they'll say, oh yeah, I used mine. They don't always share exactly how or why they used it, but it got used somehow, somewhere. And so it really does get used in the community. It's like one of those effects that you don't really, which are about like saving a life or something like that. And I think it's easy to feel that way when you code the person, the ER for two hours and you send them up for ECMO, but you'd be surprised how much these things are happening behind closed doors. You prescribe this medicine that's a life saving kind of by definition, the person probably would have done well if that medicine wasn't used in the right clinical scenario. So you probably have saved more lives than you think just by doing that. - Right, yeah, it's great. And I try to tell the patients that too, if they're hesitant to have nooxone, I say, hey, you could save a life, you know? Don't you want to be that guy who saves someone's life? Carry this around and you might be that guy someday. - Yeah, this might be a little paternalistic, but I just prescribe it with the first suboxone prescription. And then I let them work it out the pharmacy if they want to take it or not. - That's probably good, opt out rather than opt in. - Exactly. So this moderate size longitudinal cohort study does provide some evidence that receipt of take hemoloxone training has known statistically significant effect on many surrogate patient-centered outcomes of substance use disorder, including injection drug use, frequency opioid injection frequency, use of drugs alone and benzodiazepine use frequency. I think my only concern about it is, I love the study and this is not a critique. I just feel like that there is a group that kind of fights us on this, right? They fight the idea of safe injection sites, they fight the idea of naloxone distribution, they fight the idea of kind of like risk mitigation behavior. And I don't know if 189 patients is gonna be enough to kind of make the non-believers believers, but I think it's a good start, right? Definitely. - Yeah, I mean, you have to start somewhere. - Yeah, I think that in summary, please prescribe naloxone, everyone on the call. I think everyone on this podcast, please prescribe it, please prescribe it to appropriate patients, family members and friends. With or without a take on naloxone training program, it's relatively easy to use, it can save a life. I think that we have robust data that it's effective at decreasing death at a population level in a community. And there's really an absence of data, like a total absence of data at this point that you're actually harming any patients. So please prescribe. - Well, and at this point at this recording date, it is now available over the counter. And so people can buy their own naloxone. It's much more expensive. So in our area, people's insurance usually covers it and they don't have to pay much or just to stand or copay. And if you're buying it over the counter, it's a lot more expensive. But anyone who doesn't want it sort of officially on their record that they got naloxone can just buy their own. And that's been true in the state of Pennsylvania for a while, but now it's over the counter in general. John, this is just coincidence, but I have to give a shout out to two other addiction podcasts because I listened to two addiction podcasts today as I was commuting to and from work about overdose prevention with naloxone. And they were both awesome. And so I just have to share the podcast love. And so one is this amazing podcast called Addiction in Emergency Medicine and Acute Care. And the other one is the Curb Siders Addiction Medicine. They both have great episodes on overdose prevention with naloxone. So if you want to know more, especially using naloxone in clinical practice, listen to those two podcasts. So thank you for listening to the Addiction Medicine Journal Club. The best part of any journal club is the conversation. And we really do want to hear what you have to say. If you have any opinions about the articles, please send them to us. And I would love to put your comments on the air. You can talk to us on Facebook, on what used to be called Twitter, on YouTube. And if you listen on Spotify, there's a little spot with each episode where you can leave a comment. You can also email us and join our Facebook group. If you know us in person, you can just find us and tell us stuff or come to our live journal club that we host at St. Max's. So all the links on how to reach us are in the show notes and we really hope you'll reach out with comments. Our original theme music was composed and performed by Benjamin Kennedy, audio editing by Aaron McQ. 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