Hello, I am Dr. Amy Ewell. On behalf of the American Psychiatric Association, welcome to today's webinar, Opiate Use Disorder in Women. Today's activity is presented on behalf of the SAMHSA-funded Provider Clinical Support System, a program operated collaboratively by 19 medical specialty organizations, including the APA. Next slide. Slides from the presentation today are available in the handouts area, which is found in the lower portion of your control panel. Please select the link to download the PDF. Next slide. And today we'll reserve 10 to 15 minutes at the end of the presentation for Q&A. Please feel free to submit your questions throughout the presentation by typing them into the question area, which is also found on the lower portion of your control panel. And next slide. Now I'm really honored to introduce you to the faculty for today's webinar, Dr. Kathleen Brady. She's the Vice President of Research at the Medical University of South Carolina. Her research expertise lies in addiction research, substance use disorders, and mental health, as well as relationships among gender, stress, and drug addiction. We are thrilled to have Dr. Brady here with us today on such an important topic. I welcome you to today's session, Dr. Brady, and thank you for leading today's webinar. Thank you so much. It's a pleasure to be here, especially since I think this is Women's Day. So I think this is a particularly, International Women's Day, this is a particularly appropriate topic, and I'm pleased to be here. So let me just begin by saying that I really don't have any financial relationships or conflicts with regard to this particular presentation to report, and that the overall overarching goal of this webinar is to train healthcare professionals in evidence-based practices for the treatment of opioid use disorders, particularly medication prescribing and prevention and treatment of substance use disorders. In terms of educational objectives, at the conclusion of this activity, participants should be able to apply the epidemiologic differences in the prevalence of OUD to your practice setting, to identify gender differences in the neurobiology of OUD and make that useful when treating patients and evaluate patient outcomes based on gender. So I'm gonna start with just some general principles in terms of gender differences in drugs of abuse. And throughout this presentation, you're gonna see me going back and forth between some general things about gender differences in substance use disorders, because there are some things that apply across substances, and then into specifics about opioid use disorders. But if we look across substances, men, and this statistic has been about the same for many years, at least 30 years, men are two to three times more likely to have an alcohol use disorder as compared to women. And men are one and a half to two times. So the gender differential in terms of cocaine, illicit opioids, marijuana use disorder is a little bit less than alcohol. Men slightly more likely to have nicotine dependence, but women, and this has been, again, this gender difference has been in existence for at least 10 to 20 years, are more likely to have a prescription drug use disorder compared to men. So women are just generally more likely to, and have been for 20 to 30 years before the opioid epidemic really struck us, and it's continued throughout, more likely to be prescribed opioids, and more likely to be on them for a longer period of time. But because of that, as the opioid epidemic really took over in the United States and drug overdose death rates increased, women were really among the group in whom drug overdose deaths increased particularly precipitously, because they were the ones most likely to be on opiates. So women aged 30 to 64 increased drug overdose rates by 270% from 1999 to 2017, and this was significantly higher than the rate of increase in men. And now, over the last two years, women are now using heroin at similar rates than men, and this has increased significantly over the past four decades. In terms of perinatal, which we all know is a significant problem, 2.3% of women of reproductive age reported non-medical opioid use in the last 30 days, and 0.8% of pregnant women reported non-medical opioid use. There's been a five-fold increase in neonatal opioid withdrawal syndrome between 2004 and 2014, so that data is a little old, but still what you see and what you hear is that there's a huge increase in neonatal opioid withdrawal. And in one sample, 0.4% of pregnant women at the time of delivery had opioid dependence or misuse. So one of the questions, and particularly when it comes to overdose by women, is have we overcorrected in terms of prescribing? And I'm just gonna give you a little vignette in terms of our experience in South Carolina, a very rural state, and one of the things as the opioid epidemic increased and as there was more of a crackdown in DEA, and with the PDMPs, which I think are wonderful, it's good to know who are your high prescribers but a lot of primary care physicians really got spooked about prescribing, and particularly in, I can tell you, in South Carolina, in rural areas in South Carolina, we were trying to do academic detailing to improve knowledge about opioid prescribing and also to see if there was any interest in people learning how to use buprenorphine. And a lot of primary care physicians said, we have stopped prescribing opioids, we no longer prescribe in our practice. And so I think the crackdown physicians around 2015 and 16 got the message and actual opioid prescribing went down fairly precipitously around that time as the guidelines and regulations and stuff ramped up. Some people just decided to get out of prescribing completely but unfortunately, what that meant was that many people who had been on opioids for chronic pain and maybe on escalating doses, but rather than be tapered off or switch to buprenorphine or some other more reasonable strategy, people were abruptly discontinued and their physicians just said they're not gonna prescribe anymore. Fortunately, the new CDC guidelines, I think, recognize that for one thing, for instance, in South Carolina, our governor stepped in and said only five days, now there was no way of enforcing it, but he said after surgery, you cannot prescribe more than five days of an opioid. Now, think about somebody with multiple traumas who goes home and is gonna have a hard time getting back but with a legitimate need for pain relief, having a hard time getting back and forth. So the new CDC guidelines actually, it's in the comment period right now, guys, so you should take a look. They're posted right now. You can make a comment until April 11th, but they certainly recommend the use of alternative strategies and non-pharmacologic as well as non-opioid when you're in taking pharmacology, when you decide on pharmacotherapy. But one of the big issues is that they talk about how this needs to be a clinical decision based on patient characteristics. And some of these arbitrary numbers about how often or how much you can prescribe really can't be applied across populations. So I'm hoping that, and I think we have overcorrected to some extent, I'm hoping that will be, I'm hoping the guidelines will help us to sort of scale that back a little bit. But just in terms of why this overcorrection in prescriptions might've had such an impact on women, it's because women were more likely to be prescribed opioids and to be prescribed opioids chronically. So when there was a huge crackdown and if some physicians behaved in ways that we might've thought could have been improved, it's gonna be females that are gonna be more likely to be impacted on this. So between 1999 and 2015, prescription opioid overdose increased by 471% in women versus 218% in men. Between 2002 and 2013, 100% increase in heroin use in women compared to 50% in men and an 850% increase in synthetic opioid related deaths for women. So clearly women turning from their prescription opioids to illicit and very dangerous synthetic opioids. What gender differences in opioid use disorder are different from the differences in, gender differences in substance use disorder in general? Well, the death rate is unprecedented and rising among women, although I think during the pandemic, as we know, we saw huge increases. Those were more gender equal between men and women. Opioid use disorder in pregnancy is increased tremendously with an unprecedented increase in the rate of neonatal withdrawal. Rise in unrecognized suicide in opioid poisonings overall contributing to deaths. It could present 10% of suicide deaths in women. Certainly, we've just gone over the differences in opioid overdose death by gender. And women with prescription opioid use disorder are more likely to have chronic pains, psychiatric comorbidity, and decreased functional status. All of those things which need to be addressed when trying to taper and or switch their medication. Okay. What are the gender differences that are the same in between opioid use disorder and other substance use disorders? Well, I'll now show you some more data about this. Women definitely have higher rates of co-occurring psychiatric disorders, in particular, things like depression, anxiety, and post-traumatic stress disorder. There is this telescoping course of illness that's been shown across substance use disorder. And certainly, for alcohol use disorder, we know there's a biologic reason for it, but they suffer physical sequelae at much lower doses than men do. Women have a higher rate of co-occurring psychotic disorders. They have a higher rate of co-occurring psychotic disorders. than men do. Women are, for all substance use disorders, less likely to receive treatment, less likely to go into treatment. A couple of reasons for that, including barriers such as childcare problems, which are more problematic for women than men, insurance status often lower in women than men, and gender-specific barriers to treatment for all women across substance use include these co-occurring disorders, trauma and the effect of current and ongoing trauma, financial vulnerability. Women are much more likely to have a partner who's using as compared to men. Less social support for recovery, pregnancy and parenting, and stigma and discrimination, which is certainly an issue for both genders, but particularly for women of childbearing years and pregnant women, stigma is a huge issue. It hugely discourages treatment seeking. I just wanted to show you, this is actually lifetime drug dependence and people with, so this is across substances, but we're looking at anxiety disorder, affective disorder, and co-occurring more than one drug. And what you can see is that women are twice as likely as men to have an anxiety disorder, twice as likely to have a mood disorder. Drug dependence or polysubstance is how I need to change this. Polysubstance is about the same for men and women. Opioid use disorder is currently a risk for co-occurring mood disorders. 54% have a mood disorder, about 45% depression, 15% dysthymia, and then mania or bipolar disorder. Odds ratios are pretty big with women being five times as likely to have a mood disorder compared to men and almost four and a half times as likely to have major depression. So really need to look for this comorbidity with mood disorder and anxiety disorders. 36.3 of individuals with opioid use disorder have anxiety disorders, but for women, this is actually higher. Three times as likely, women are three times as likely to have any anxiety disorder, almost five times as likely to have panic, agoraphobia, three times as likely to have social phobia or GAD. PTSD is an area that's been of particular interest for my research group, and PTSD is associated with an increased risk for substance use disorders for both genders. But the relationship is stronger for women than it is for men. Women are likely to have more of the symptoms in the avoidance cluster, men are more likely to have symptoms in the arousal cluster, and that really does suggest that there may be different. If you think that PTSD is leading to use, there could be different reasons for use in. Men may be using to calm down, women may be using to sort of face the world as they need to face it. But one of the things of particular interest is the fact that childhood, the relationship between childhood adversity and addiction is something that has been shown in numerous studies, but it is definitely, and it occurs for both genders, but it is definitely a stronger relationship in women than in men. Ken Kendler's study showed that substance use was the strongest and it outweighed all sorts of environmental factors in terms of the development of addiction, that childhood sexual abuse for women was the strongest predictor of addiction and it outweighed all sorts of environmental factors. But this is a great study, you've all heard of it, it's the Childhood Adverse Experience Study done by University of San Diego and RAND, and it's almost 10,000 people, they basically gave them a very nice survey looking at all kinds of childhood adversity. At this point, this was a long time ago, we were focused very much just on severe things like sexual abuse, but this survey was great because it really covered not just big traumas, but did you move a lot? Was there alcohol use in their house? So you got a more graded view of the level of adversity, but what you can see is that these ACE scores, once they get above a certain level, four to five traumas account for one. one-half to two-thirds of serious problems with drug abuse. If you look at the odds ratio of initiating drug use early, rather than ever being addicted due to high adverse childhood experiences and the development of addiction. This is a study, again, as I said, I'm flipping back and forth. We're talking about cocaine relapse here after treatment in men and women. What I want you to see on the left-hand side right here, we're looking at the probability of staying relapse-free after treatment in women who have experienced high emotional abuse or low emotional abuse. What you can see is emotional abuse is definitely associated with early relapse in women, but not in men. These childhood traumas particularly impact women and have been shown to be associated with early relapse, particularly, again, this is an older study, particularly, if they're not addressed in treatment. One of the things my group's been really curious about is why, on Earth and how, what's the physiologic mechanism by which early things that happened to you very early in your life impact the way you behave 10, 15, 20 years later? Of course, in this area, the field of epigenetics, I think, is going to offer the addictions world a great deal in terms of explaining. Once we have some interventions that can actually impact epigenetic changes, I think psychiatry in general, substance use disorders in particular, I think really stand to benefit. But basically, these are environmentally induced changes in DNA expression. As you know, these histone bodies at the end of this tightly coiled DNA helix, if you methylate or acetylate, you can open up the double helix for more transmission, more mRNA, and more protein, or you can close it down and make it less likely that the protein encoded is going to be expressed. That's what those epigenetic changes do. One of the things, I'm not going to show all this data, but I am going to talk a little bit about what we know about epigenetics and gender differences. But people have looked at the CRH receptor in the stress system, and there are polymorphisms of that CRH receptor, some of which are more or less susceptible to epigenetic changes, and those are very much associated with developing addictions in individuals with childhood trauma. This was a very interesting basic science study which shows sex differences in epigenetics in the nucleus accumbens transcriptome, subchronic variable stress in male and female mice, with markedly different patterns of stress regulation of gene expression, in which the females with this stress showed more signs of depression and greater methylation. But when they knocked out the DNA methyltransferase in females this enhanced their resilience and they looked more like men in terms of the depression, more like males in terms of the depression. It looks like epigenetic changes, which is probably one of the mechanisms by which these early traumas impact people's responses and behaviors later in life are very much differ by gender. I want to talk about stress and differences in the response to stress. We have a P50 center that's focused on gender differences and substance use disorders, and we've really been at the intersection of gender differences and stress response in people with addictions for a long time, and started out with a lot of Q-reactivity, human laboratory paradigms and showed as we did, as have many others, that women have greater craving to negative emotional cues compared to men, that women will much more often endorse things like stress and interpersonal conflict as a precipitant to their relapse, but that men are more responsive to drug-related cues, so environmental cues associated with their drug use. This clearly has great implication in terms of how you might treat substance use disorder differently in men as compared to women. Let me just say that my friend Mark Potenza did a beautiful study that really eclipsed all of this human laboratory without imaging. What he did was compare. This is a fMRI study. We're looking at normal controls versus, again, it's cocaine dependence, but you'll see, I think the stress response difference is also existing in opioid use disorder. But on this right-hand side here, we're looking at the difference in cocaine-dependent women versus healthy control women, when you show them a stress-related cue in the MRI, when you show them a drug-related cue in the MRI. Clearly, stress lights up for cocaine-dependent women, all kinds of areas that we know are associated nucleus accumbens, midbrain area, we know to be associated with substance use as well as cortical activity. But drug cues don't really seem to make a big difference between cocaine-dependent women and controls. For men, what we see is pretty much the opposite. You show them a drug cue and you see all kinds of activity in areas that are related to, we know the craving and experience and memory of drug use, whereas the stress cues don't seem to have nearly the same impact in terms of brain activity. We've done some imaging studies, but we do a lot more human laboratory neuroendocrine. What we're measuring is the stress axis. As you know, CRF or CRH, corticotropin-releasing hormone, comes from the hypothalamus to the pituitary, where ACTH is released from the anterior pituitary. At the same time, oxytocin and beta-endorphin and other more anti-stress hormones are released from the posterior pituitary to help with the yin and yang of the stress response. ACTH goes to the adrenals where cortisol is released. Cortisol, actually, one of the things it does is, there's a lot of intricate feedback loops here. Cortisol goes back and actually helps through feedback, shut down the pituitary and the hypothalamic response to stress. The cortisol peaks about 20 minutes after a stress. But one of the things that CRF does also, in addition to stimulating the hypothalamus, there is a locus coeruleus, noradrenergic stimulation that also goes to the adrenals. A different part of the adrenals then releases norepinephrine and epinephrine, which lead to the fight and flight and heart rate and all those increases. Cortisol comes around behind and shuts that down because you figure, most big stressors, you're probably ready to return to your normal level of vigilance and excitation in 20 minutes if the stress is not a constant and ongoing thing. We have done a similar study to this across opioid, cocaine, nicotine, marijuana, and alcohol-dependent. What we do is bring people in, cocaine-dependent or opioid-dependent and controls into the human laboratory. They're clean at the time of the testing. We usually do a stress, we usually have a stress condition, we usually have a drug cue condition. Often we've got pharmacologic agents on board that may be designed to decrease the stress or help in other ways. What we measure after that is, and this is the TRIER, it's a social speaking task, which is very stressful for almost everybody. If that's not stressful enough, it's followed by math computation that they have to do in their head for like five minutes while the people that are watching them keep correcting them. It's very stressful. What we measure over time is their subjective response to the stress, their subjective response of craving. We measure heart rate, cortisol, epinephrine, norepinephrine. We're looking at those neuroendocrine markers. Right here, what we're looking at is just their response to this social speaking task in opioid-dependent men and women. You can see the females have a significantly higher response than the males. That's their subjective stress and their craving looks pretty much the same. This is the cortisol response, and I'm sorry, it looks like I've got my graph is marked wrong. This is not stress, this is cortisol. What you can see is that the males have a much more robust cortisol response than the females. We have found this across substances pretty much maybe not as robust as this. Again, it's also something that you see in PTSD and early trauma, is that it's almost as if there's burnout of the cortisol system and that the response is not as robust and not. This would be lower than what you would see in a female without opioid use disorder. But then when we look at the heart rate, so again, remember one of the things that cortisol serves to do is do feedback and shut down the autonomic hyperactivity that follows the stress. What we see here, this is our cocaine-dependent women who experienced the stress and this is their heart rate. You can see it goes up higher and it stays up. This is compared to the males and the no stress, goes up and stays up. This is 60 minutes after the stressor, their heart rate is still significantly elevated, has not returned to normal. We think that one of the things that's going on here is that there's dysregulation of the HPA axis response that it is, and this is particularly to a social stressor and it's much more robust in this dysregulation really seems to impact women. As I said, we've done these studies in alcohol, nicotine, cocaine, opioid, and now marijuana-dependent women. We demonstrate more HPA axis dysregulation and noradrenergic sensitivity in women compared to men. We think this may be mechanistically connected to the high PTSD and other mood, anxiety, comorbidity in women. There's also a greater disconnect between their subjective. You saw that in that data, high subjective response in the women, but low physiology in terms of their cortisol, the HPA axis response. Actually, we and others have shown that that particular disconnect, high subjective but low cortisol response is associated with relapse. Clearly, this is something that has treatment implications in a couple of ways. For psychosocial treatment, the implications are you need to deal with stress and stress reactivity and interpersonal stressful situations for women in particular. Also, if you had an agent that you thought could help somehow in interrupting this prolonged and dysregulated stress response, it might be more impactful in women than in men. I thought we could talk about treatment now and gender differences in treatment. Basically, for agonist therapies, methadone buprenorphine, these appear to be equally effective in men and women. In antagonist treatment, naltrexone may have more side effects, particularly GI distress in women than it does in men. But then there's this whole group of adrenergic agents, clonidine, guanfacine, lofexidine. We've known for a long time that these could be used in detoxification because these are drugs that turn down adrenergic tone. They decrease adrenergic tone. But recent data actually suggests that these agents that decrease adrenergic tone may be useful beyond the detoxification period and may actually help in stress-related relapse. If this were the case, perhaps they'll be more efficacious in women than in men. I'm going to show you a little bit of this data. This is from Helen Fox in Rajita Sinha's lab. We're looking at gender differences in the impact of adrenergic blockade on craving. Again, we're talking about cocaine, but we've got similar data now with lofexidine in opioid-dependent. But what you see here is the guanfacine group is the group, it's placebo versus guanfacine. The striped bar. You can see that guanfacine in males actually looks like it might even increase craving, but in females, definitely, we see a decrease in craving that's provoked by imagery in females treated with guanfacine versus placebo. This was a very nice study done by the NIDA intramural program, where they had 120 opioid-dependent individuals who are all on buprenorphine or methadone, so they're already on agonist treatment. And one group is placed on clonidine and kept on clonidine for a couple of months versus the group that's placed on placebo. We're looking at relapse at survival analysis here, and what you can see is clonidine actually protected from relapse in this group compared to placebo. So, again, there's no gender analysis in this because there's too many men versus women, so there wasn't a significant number of women, so they couldn't do a gender analysis. But of interest, they did EMA, ecologic momentary assessment, and asked these folks periodically throughout the day, are you feeling stressed? Do you have craving? And what they found was this clonidine group here, where they particularly saw an advantage was stress-induced craving. This group reported stressful events were dissociated from craving, whereas the placebo group, when they were stressed, they were reporting craving. So we have reason to believe that decreasing the reaction to stress is the mechanism by which clonidine prolonged abstinence in this group. Lofexidine is another alpha blocker that was recently approved. It's been approved in Europe for a long time, many years, but it was recently approved in the United States for opioid withdrawal. This is just looking at the opioid withdrawal scale with lofexidine versus placebo over the first couple of days of withdrawal, and you can see that there's a significant decrease. We are now conducting a fairly large trial within our center where we're looking at lofexidine versus placebo in people. Again, it's similar to the methodology in the clonidine study I just talked about, but we've adequately powered it to look at gender differences and to look at stress-induced relapse. So our hypothesis is that lofexidine will be, and any alpha blocker will be more potent in protecting against stress-induced relapse in women as compared to men. Since we're talking about gender-specific issues, I think the MOTHER study is one that's really important to bring up, and this is the treatment for opioid dependence in pregnant women, and we know that methadone or buprenorphine have been recommended as treatments in the MOTHER study. There were 175 pregnant opioid-dependent women randomized to bup versus methadone. There were 131 neonates born. Bup-exposed infants required significantly less morphine and significantly fewer hospital days and had a shorter duration of treatment for neonatal abstinence. And that is the good news. However, there's more maternal dropout in the buprenorphine versus the methadone group. So again, we know methadone's a full agonist and can retain people. This isn't the first study that showed better retention. It's the first one that showed it in pregnant women. So the dropout was likely due to their induction protocol, at least in part, so where it was a slower induction with the buprenorphine. So this is an interesting, they are now, you know, this study is now being done looking at buprenorphine with the injectable versus sublingual to see if you can get better blood level, more consistent blood levels, and perhaps less dropout in using the long-acting buprenorphine. So what about single gender treatment? Do we need to have programs for men and programs for women? Well, I would say that in general, the findings have been very inconsistent regarding relative efficacy of single gender treatment. There haven't been a lot of good studies done. It's a hard study to do, but the findings are really not consistent. There's just, and there's just not many of those programs. I think in general, what we can say is that women do as well as men in treatment after you control for some of the issues that might be impacting outcomes that differ by gender. Things like, things we talked about at the very beginning of this talk, things like comorbidity, things like financial issues, things like parenting and home life situations that could differ and make and present as barriers to treatment. Again, the treatment programs for women I think one of the things that they do that is particularly helpful is reduce those barriers that are unique to women. Often they provide child care. Often they are, you know, especially, you know, women who are either pregnant or immediately postpartum for the first year or so do have Medicaid, so they often can help with lack of resources. Also, you know, one of the things that's really important is dealing with one's home life. Substance use as well as trauma that might be ongoing in the home really needs to be addressed. It needs to be addressed for men and women, but it appears to be a more important issue in women. Higher rates of substance use in the home for women than there is for men, and certainly more trauma. The other thing about treatment programs for women is they can certainly focus on unique health problems that women may have, things like getting pregnant and protecting against that if you need to. Parenting classes are important for men and women, but we still find that women are often the primary parents, so this is really important. Women are the primary parent often in child rearing. Often they have come from homes where good parenting wasn't well modeled for them, so these parenting classes are really important. And then certainly focusing on co-occurring disorders such as PTSD, depression, anxiety, definitely it needs to be a part of any treatment program for women. I think the bottom line is as long as a treatment program addresses these issues, it really doesn't matter if there's men and women involved. I think outcomes are going to be improved for women if you address these issues. However, I think one of the things that's of interest is that perhaps even in those programs that are mixed gender, it makes sense to have a group for men and a group for women because there are probably some unique issues by gender, and also we know that a lot of women have experienced trauma and sexual trauma, things that might be harder to discuss in a mixed gender group. So at the very least, I think it makes sense for treatment programs that have people of both genders to at least provide something like a women's recovery group. This is a very nice manual-based relapse prevention group therapy with structured session and gender-focused content. It's empirically supported and this has been studied a number of times. So this is actually a very nice gender-responsive component of care that really can be made a part of just routine clinical practice in substance abuse treatment programs. So in conclusion, opioid use disorder, opioid-related deaths continue to rise. I mean, looking at these numbers during COVID, to me, it's really been heartbreaking. Effective treatments are available and the last number I saw quoted, like 12% of people who could be on, who would meet criteria for medications for opioid use disorders are on treatment, 12%. So we have effective treatments and they're just not used. And to some extent, that's a resource issue. To some extent, it's stigma. We really need to do something about the stigma that's related to substance use disorders in general and opioid use disorders in particular because they are killing people. This says only 20% of patients are treated in general, but that's with psychosocial and everything, but only about 12% with medications. The epidemic is complex, as we all know, and changing. We saw it change. We saw it change from prescription opioids to synthetic illicit opioids. And then we saw it change again during the COVID pandemic where we really, treatment access became more difficult, once again, and the stigma around opioid use disorder, I think, also became exaggerated in a time when we had a group of health professionals that would just burn out, that were at their max in dealing with COVID pandemic. I think that made it even harder for people with opioid use disorders to get treatment. It's complicated, particularly for women, by psychiatric disorders and a rising rate of suicide. There are significant gender differences, and solutions are going to require multifaceted innovation, funding, implementation, and research. And I think, and by all means, just wider, not only wider access, but somehow we need to make effective treatment more acceptable. I mean, we really, really, I think in this next decade, we need to work on the stigma surrounding substance use disorders in every way that we can, because I think that's one of the things that decreases access to effective treatment. And I think with that, I will stop, and I'd welcome any questions. Thank you all so much for your attention. And thank you, Dr. Brady, for that very informative presentation. So we'll take a few minutes to take questions from the audience. As a reminder, please submit your questions throughout the presentation as you did, by typing them in the questions area, which is found in the lower portion of your control panel. And we do have some questions there. One question, though, that I did have for you, Dr. Brady, is you talked about, you know, stigma being a big barrier to engaging in substance use disorder treatment. And I wonder if you have advice for behavioral health clinicians in the audience about things that, if they have a patient, a female, who would benefit from specialty substance use disorder treatment, you know, kind of any tips or recommendations you would have on how they might, you know, try to engage that patient with a referral or recommendation for substance use disorder treatment? Yeah, you know, that's a really great question. So one of the things, let me just start with saying, you know, while I say stigma is something we really need to address, one of the things I think we need to do is do a lot of, a lot more research and gather more empirical evidence about what we can do about stigma. You know, I think the only evidence we really have, there's, NIH has put out a few research initiatives. I've never seen any striking results from that. And, you know, but we can look historically at disorders that were stigmatized and have somehow no longer been stigmatized. Cancer is probably the best example of it. You know, certainly tuberculosis, you know, the others. And so a couple of things. One is, I think that once we've got more effective treatments for a disease and once people know there are more effective treatments for disease, I think that's one thing that really helps with stigma. So, because I, you know, I think when cancer was so taboo, almost getting cancer was a death sentence. When tuberculosis was taboo, it was not only infectious, but getting tuberculosis was more or less a death sentence. So I think that's one of the things. We have effective treatments, not enough people know that, you know, too many people think of this as a hopeless situation. So I, you know, I think that's one of the first things I would do if I was trying to talk somebody into treatment. I would say, well, first of all, you probably try to use some motivational interviewing and because the person would probably say, you know, I don't really have a problem. And then you could just, you know, sort of gently probe what's going on at home, what's going on with their kids. Do they think if they have kids, could they be doing things better or their spouse or significant other? And I think you can often, that women in particular will often be persuaded by this idea that they could be doing things better in the world around them and for the people that they love. But then I also think just stressing, there are effective treatments. You can get better and you can live a better life and you can be your whole self. This is not a hopeless disorder. And if you're, you know, secretive and shut down about it, it's not going to get better. So I think I'd probably start there and see what I could do. And those are great suggestions. Thank you. And as we think about efficacious treatments, there's some questions about clonidine and your comments about clonidine earlier in the presentation. And one was just in some of the studies that have demonstrated that clonidine prolongs abstinence. Just whether you happen to know details about the dose of clonidine that was used and then also the dosing during the day. So was it daily or BID or TID? I don't know if you know any of those details. I can't remember the exact details right now, but I know it was BID. And I'm thinking that it might have been a higher amount at night. And the only thing I can tell you, I know we are working with lofexidine. And right now I'm trying to get between four and eight milligrams a day. We are definitely having, and it's a TID dosing. And so the blood pressure problem is a big one. It's a big one. It's a potential with any of these adrenergic blocking agents. And so I think two ways to get it. So you do really need to monitor it at least initially. And I actually think clonidine, I'm wishing now that we had worked with clonidine instead of lofexidine. Lofexidine seems to actually be a little bit worse in terms of, although that's not how it was advertised, but in our hands. So I would suggest that you certainly watch blood pressure carefully. And if needed, just adjust the dosing. We've had to adjust dosing much more for women than for men. And we also tend to sort of, if we're going to do anything, when we try to increase, we'll increase the evening dose before the morning dose, just because of blood pressure concerns. That's been the biggest side. We really haven't had much else in terms of side effects. Okay, great. Thank you. There's another question about treatment with buprenorphine during pregnancy in terms of using sublocate and whether or not there's any dose, there's been any data on dose adjustments with using sublocate during pregnancy. Not that I'm aware of. Okay. Okay. That's not necessarily my area of expertise, so. Got it. And then there was another question about just, as we think about harm reduction, just any special considerations that you think about in terms of gender as we try to engage patients in harm reduction or harm reduction strategies? Well, I can't, that's a good question. I can't really think of any gender specific. I'm just trying to think through what I know about that and if I have seen anything that would suggest. I'm not aware of any gender differences in terms of harm reduction strategies. Okay. But I know that women definitely tend to be more, in general, more social and can be influenced by social settings. So I'm wondering if there isn't some way you could build on that to enhance harm reduction, the uptake of harm reduction for women in particular. Yeah, and I guess one thing that comes to my mind is just thinking about with harm reduction, we're trying to get people to not use alone. And if a woman might be in a relationship where there's a risk of violence or they've been potentially using with their partner who has been violent towards them, they're just trying to think through that and support them in using around somebody else. But that's a good point. That's a very good point. Said than done. But and then there was another question just thinking about actually about men and gender specific groups. And the question was, do men do better in groups with women as opposed to in single gender men groups? What a great question that is. Again, I'd say I don't think there's a lot of data on it. So let me just say what I'm going to say is just sort of off the top of my head. But I can tell you that one of the things that Shelly Greenfield has done is she's run she's actually had some men involved in some of her groups. And the men report that they do feel like they can get more out of those groups. You think about a group with men and women together, there's probably more allowance for some of the softer emotions to be expressed and talked about. And maybe even things that are not like anger and scorn, but more like just the sadness and the depression and the shame that go along with substance use disorders. So I would think that men might benefit from groups. I think both people, both genders benefit from groups that have people of both genders in them. But I do think that in men only groups, and I think about my VA groups and sort of the VA groups that I used to run that were mostly men. And there was a lot more confrontation and anger than I've generally seen in mixed gender groups. Got it. And one question I had, you mentioned parenting groups being very, can be a key component of treatment for women. Have you seen those parenting groups present or being part of substance use disorder treatment or more typically offered outside of the substance use disorder treatment setting? Because I think with some of the women that I've worked with, at least in terms of my experience, they're often kind of have appointments with five different agencies at five different times. And it can be a challenge and didn't know if you've seen innovative programming or things that have worked well. Yeah, no, I totally can relate to that situation where, and especially if there's DSS involvement and a whole nother set of people that are assessing what's going on. But no, we've got generally have included parenting groups as part of our program. And in particular, I'm thinking for a long time, I was involved with a program that was for pregnant and women and women with young children, and it was residential. So parenting was a big part of the program. Not only didactic groups, but also sort of more show and tell and experiential work around parenting, handling infants, handling disciplinary situations and that sort of thing. Actually, I thought it was enormously helpful. Makes sense. And then there's one pharmacology kind of specific question, which was related to someone mentioned that they have two to three women with an opioid use disorder who've been doing well on less than one milligram of buprenorphine per day. And they have all told this provider that it helps them with their depression. And so they were asking a question about whether or not there's data on buprenorphine, treating depression in pregnancy for women, or if you've seen any data about that. There is a lot of data on buprenorphine and depression. I haven't seen a particular, you know, nobody does studies on pregnant women. It's very hard to do studies on pregnant women. So, you know, that's usually an exclusion. But there's a whole body of literature that looks at buprenorphine and other, buprenorphine has some kappa agonist properties, and they're looking, looked at that in depression. And usually just as an adjunct to other antidepressants in treatment resistant, but some very positive data on that. I think the issue is just sort of the risk benefit ratio of getting, you know, if you've got alternative treatments for depression, would you turn to, you know, a partial opiate agonist rather than another drug, which doesn't have any potential for abuse or dependence? Got it. Okay. Well, I think that covered a lot of the questions that came in through the chat. And, you know, we're, again, just really thankful that you were available to talk today on International Women's Day and that we got a chance to talk about this important topic. I want to go through a couple of other slides just for the audience. And if it's possible to switch to the next one. So, so please, for the audience, visit PCSSnow.org and see the variety of helpful resources that are offered, including free PCSS, the free PCSS Mentor Program, which offers general information to clinicians about evidence-based clinical practices in prescribing medications for opiate use disorders. And the next slide. And then PCSS mentors have expertise in medication for substance use treatment and clinical education. You can also find the PCSS discussion forum, which is a simple and direct way to receive and answer questions related to medication for substance use treatment. Next slide. And then an important component of this talk as we end in terms of housekeeping. If you complete an evaluation of today's session, you can obtain free CME or a certificate of participation. Attendees will receive instructions via email within an hour after the webinar concludes. The email will have a link to the evaluation survey, which you'll need to complete in full. And once you complete the evaluation survey, you'll be automatically directed to the credit claim page. And if you have any issues claiming credit, please reach out to educationme at psych.org, which is here in the slides. And then additionally, today's session was recorded. And so the presentation slides and video recording will be posted on the PCSS website in two weeks following today's live event. And next slide. And then lastly, today's activity was presented on behalf of SAMHSA funded PCSS, which is a program operated collaboratively by 19 medical specialty organizations, including the APA. And again, we just really want to thank you for joining us today. And we hope to see you soon and thank Dr. Brady for her time and her expertise that she shared with us today. Thank you.

Opiate Use Disorder in Women

American Psychiatric Association

SAMHSA-funded Provider Clinical Support System

evidence-based practices

gender differences in substance use disorders

opioid epidemic

neurobiology of opioid use disorder

accessing treatment

gender-specific considerations in treatment