false
Catalog
Treating Bipolar and Alcohol Use Disorders: Break ...
Presentation And Q&A
Presentation And Q&A
Back to course
[Please upgrade your browser to play this video content]
Video Transcription
Hello, and welcome. I'm Dr. Amy Cohen, a clinical psychologist and the director for SMI Advisor. I'm pleased that you're joining us for today's SMI Advisor webinar, Bipolar and Alcohol Use Disorder, Break the Magnetic Force. SMI Advisor, also known as the Clinical Support System for Serious Mental Illness, is an APA and SAMHSA initiative devoted to helping clinicians implement evidence-based care for those living with serious mental illness. Working with experts from across the SMI clinician community, our interdisciplinary effort has been designed to help you get the answers you need to care for your patients. Today's webinar has been designated for one AMA PRA Category 1 credit for physicians, one continuing education credit for psychologists, one nursing continuing professional development contact hour, and one social work continuing education credit. Credit for participating in today's webinar will be available until August 23rd, 2021. Slides from the presentation today are available in the handouts area found in the lower portion of your control panel. Select the link to download the PDF. And please feel free to submit your questions throughout the presentation by typing them into the questionnaire found in the lower portion of your control panel. We'll reserve 10 minutes at the end of the presentation for Q&A. Now I'd like to introduce you to the faculty for today's webinar, Dr. Javier Ballester. Dr. Ballester is an Assistant Clinical Professor at the University of Utah School of Medicine. Dr. Ballester is board certified in psychiatry and in addiction psychiatry by the ABPN and in addiction medicine by the ABPM. His current interests include research in neurobiological mechanisms of substance use disorders, mood disorders, education, and psychiatry services to minority populations, specifically the Hispanic and Latino and LGBT populations. Dr. Ballester, thank you for leading today's webinar. Thank you very much, everyone. I'm very excited to be here. Good morning to you all. Let's going to start the presentation. First of all, I wanted to show that I have no financial relationships or any conflicts of interest to report. And these are the learning objectives for the presentation, which are describe the epidemiology and the strength of association of bipolar and alcohol use disorders to summarize the clinical outcomes when such comorbidity is present and discuss the different FDA approved pharmacological and psychotherapeutic treatments for the management of alcohol use disorder and how we can combine them for the treatment of this comorbidity. So the presentation has five sections, and let's going to start with section number one, where I'm going to just present a few epidemiological data on this dual comorbidity. So this is data from the National Survey on Drug Use and Health, or NSDUH, which is an annual nationwide survey of both legal and illegal drugs, as well as mental disorders, and is conducted by the US federal government, has been done since 1971, and it is funded by the Substance Abuse and Mental Health Services Administration, or SAMHSA. The survey, just so everyone has a little awareness, interviews 70,000 American civilians and non-institutionalized age 12 and older through face-to-face interviews. And this interview, this survey, along with the Monitoring the Future, are the two main ways that the National Institute on Drug Abuse, or NIDA, measures drug use in the United States. So you can see two figures here. The first figure, or figure 37 from the document, shows the alcohol use disorder in the past year among people age 12 and older. And you can see that the percentage with a past year alcohol use disorder in the group of 12 and older, in general, declined from 7.7% in 2002 to 5.3% in 2019, which is good news. And figure 38 shows on the right, again, four age groups represented by different lines. And we can see that among people age 12 or older in 2019, 3% had at least one illicit drug use disorder in 2019. And these estimates are very similar since 2015. So what we can see is that in general, there's been a decrease in the prevalence of alcohol use disorder in a population level for the past decade. But the prevalence of illicit drug use disorder remains stable. And so people are also aware, these percentages reflect the prevalence in the last year, but this is not the lifetime prevalence, which obviously it will be much higher. So the following figure shows a pie graph. In this case, I'm showing the percentage of people with a past year substance use disorder compared to those people with no substance use disorder in the past year. And the right side, there is a bar graph that breaks down the people with a substance use disorder. And what we can see is that approximately 14.5 million of people had an alcohol use disorder compared to 8.3 million who had an illicit drug use disorder. And you can see displayed all of some of the most important illicit drug. The 8.3 million graph represents the sum of all of the other ones. So we can see that marijuana use disorder is the illicit drug most widely used, followed by pain reliever use disorder and then methamphetamine use disorder. So still we can see that alcohol is the main substance use disorder in a population level. So what about, I talk about drug use disorder, but what about mental, serious mental illness? So first of all, it's important for people to know that SAMHSA defines serious mental illness as people suffering from bipolar disorder, from schizophrenia or from major depressive disorder in the severe modality. So in this figure, also taken from NSDOH report from last year, we can see that among adults aged 12 or older, the percentage with past year serious mental illness increased from 3.7% in 2008 to 5%, more than 5% in 2019. And these estimates are increasing in all of the age groups, as you can see, but especially concerning is the increase in the group of adults between 18 to 25 years old. And this is known as the transitional age youth. So this is not good news. And these increases can be explained by a higher incidence of major depressive disorder. So in this figure, there is a Venn diagram that shows overlapping larger and smaller circles. And the larger circle on the left represents adults with substance use disorder in 2019, but without serious mental illness. And the smaller circle on the right represents adults with serious mental illness in 2019, but with no substance use disorder. And you can see the intersection of the two circles represents adults who have both serious mental illness and substance use disorder. So it is important to know that approximately 1.4% of the population of the United States had both serious mental illness and substance use disorder combined. So the prevalence, the dual comorbidity is pretty high. And another way of seeing this is that it's reflecting this data. I'm pointing out that the high comorbidity between these entities could also be summarized into the sentence that more than one out of four or 27% of adults with serious mental illness have a substance use disorder. And this is excluding nicotine. So what about the treatment? What are we doing in relationship to the treatment of these people? Well, these are data of the treatment of substance use at a specialty facility and mental health services in the past year among adults age 12 or older with both substance use disorder and serious mental illness between 2015 and 2019. And I want you to pay attention to the bottom line, the blue line that reflects the prevalence of people receiving treatment, the percentage of people receiving treatment in both substance use disorder treatment and mental health service combined. And this is approximately 12.7% of people of suffering from both serious mental illness and substance use disorder are receiving combined treatment at a specialty facility and mental health services. So this is not good. And only 12% are receiving combining treatment in specialized services. So this is an overview of where are we epidemiological data on people with substance use disorder and serious mental illness and their treatment. So we are more interested in this presentation about people with bipolar disorder and alcohol use disorder. So if we want to find out the prevalence of these both comorbidity, we need to record to other epidemiological studies. So the first one, one of the most important ones that have been done in the United States is called epidemiological catchment area. And that was done in the early 80s. And it was really a major hit in psychiatric epidemiology because the sample size was very large, 20,000 people. It was multi-site. People used for the very first time standardized criteria and they used the diagnostic interview schedule based at that time on the DSM-3 publication. And they also did a one-year longitudinal re-interview to show the incidence. So it was done, like I said, multi-site in different cities and universities. And what is more important for us to know is that besides antisocial personality disorder, what was found in this large epidemiological study is that bipolar disorder had the highest rates of substance use disorder compared to any other major psychiatric disorder. So among the axis one disorders at that time, bipolar disorder was the highest one associated with substance use disorder. In fact, they found that the prevalence between any bipolar disorder and alcohol use disorder was 43%, which is extremely high. The National Epidemiological Survey on Alcoholism and Related Conditions or NSARC is conducted by the National Institute on Alcohol Abuse. And this is data that are more recent. And the third wave that they call was done in more than 36,000 people older than 18-year-old. It was done in 2012. And once again, except for alcohol use disorder and substance use disorder that happened combined more often than not, the highest associations were found between alcohol use disorder and bipolar disorder. So studies done, what about studies? I have talked about epidemiological studies, but what about studies in clinical population? They can also help us to provide some light into the association between alcohol use disorder and bipolar disorder. So one of the most important studies done in this regard is called the Systematic Treatment Enhancement Program for Bipolar Disorder or STEP-BD. And it's a multi-site study that enrolled more than 4,300 people between 1999 and 2005. And it is very unique because it combines both randomized clinical trials and uncontrolled evidence-based clinical care, regular clinical care, because their intention was something that would be generalizable to routine clinical care. It was found that the lifetime prevalence between bipolar and alcohol use disorder was found to be 32%, which is lower than the 43% found in the epidemiological catchment area that I talked about before. And a potential reason for this could be that the ICA also included institutionalized population. And this population typically suffers from higher severity. And the most recent one, and this is the last slide on epidemiology on section one, shows two more recent systematic reviews. The first one, they were both done by the same group. And the first one combined clinical studies done in clinical settings in the United States, both inpatient and outpatient settings. And once again, the prevalence of alcohol use disorder was found to be 40% with bipolar disorder. So this finding is replicated over and over in epidemiological and clinical studies. The same group also have performed, this is interesting, another systematic review in national and international surveys of general populations, also in the same range between 1990 and 2015. And in this case, the prevalence was found to be lower, 24%. Why is this in an international level? I don't know, but it could be explained by different methodologies. But it could also be that Asian countries tend to have lower prevalence of alcohol use disorder compared to the Eastern, Western countries. So the conclusions on section one is that alcohol use disorder is the most prevalent substance use disorder in the population. More than 5% in the past year suffered from this disorder. More than one out of four people with serious mental illness suffered from a substance use disorder, not including nicotine. So this is the importance of the comorbidity that I am trying to explain. And only 12% of this population received integrated treatment. So we are not doing things right. And bipolar disorder is the most prevalent serious mental illness with an alcohol use disorder, up to 40% in population and also in clinical studies in the USA. So let's move now to section two that I entitled Magnetic Association with Clinical Consequences. And I showed bipolar magnet to show the attraction that it can have to alcohol use disorder. So let's now focus more in clinical data. And the first question that I had is, is there any sex differences in this comorbidity between bipolar and alcohol use disorder? And there has been different studies in this matter, and all of them seem to converge into that alcohol use disorder is more frequent in males with bipolar disorder versus females. This is the case of those studies done by PRI with the Stanley Foundation Bipolar Network. Similar percentages, approximately 40% in men compared to 20% in women were found in this meta-analysis done by DeFlorio. So pretty much double percentage in men versus women. And a more recent study published by Shaw in outpatient sample of more than 200 people in Sydney found that after a multivariate regression analysis, alcohol use disorder in the case of bipolar disorder was associated with being male, younger and having other substance use disorder. What about taking into account bipolar subtypes? As we know, there are different types of bipolar, there is type one, type two, there is bipolar NOS or unspecified now, but there is also what people know as the bipolar spectrum. So there has been clinical relevant data assessing this difference in the association between alcohol and bipolar. And the earliest studies done at the beginning of 2000s in the USA found a higher prevalence of alcohol in bipolar disorder type one compared to type two. These are the study of the group by and also similar results were found by the group of Fry that I talked about before. However, other people have not found this association, but this one is the study that I mentioned before by Shaw in Australia. So I want to talk a little bit about the COGA dataset, which stands for collaborative study on the genetics of alcoholism. This is a study created in 1989 by the NIAAA and the intention was learning more about the genetic vulnerability to alcohol use disorder. So researchers who use this data have been following families with a large prevalence of alcohol use disorder and at six major cities. And there is data in more than 2000 families, including more than 17,000 individuals. So I think one important to know is that one of the advantages is that this is one of the few prospective studies that have differentiated people with bipolar versus one versus bipolar type two. So why am I presenting this data? Well, I want to show what happens in the follow-up of these people who suffer from this comorbidity. So this is a recent analysis done using this dataset in more than 200 individuals with this sample. The group by Prus identified four groups. The group number one included people with bipolar type two only, only 20 people. Group two, including people with bipolar two and alcohol use disorder, in this case, 56 people. Group number three included people with bipolar only one disorder and group number four included people with bipolar one and alcohol use disorder. In this case, the sub-sample was larger than the other ones. So they measure different, they did different assessments at baseline and five years later. And what they found is that the group four, so that group that includes bipolar one and alcohol use disorder combined, had more depressive manic episodes, more suicidal behavior, and less social functioning. So this is one of the first studies that started to show us a red flag of what happens if we find people having bipolar type one and alcohol use disorder. So it's very interesting also. Something that we have found is that the order of appearance of this comorbidity might impact the outcomes. So there are at least two studies that I'm going to present that seem to reflect the fact that this commutative property that we use in math might not apply here. So this first work that I'm presenting here, and you can download the slides and pay more attention to this, but the first work by Strakowski found differences in time to recover in patients with bipolar type one who had been first time hospitalized after a manic or mixed episode and follow up up to five years. So patients who had already an alcohol use disorder before the beginning of the bipolar disorder had a faster, actually, recovery than the other groups. So, however, the bipolar first group, so those people who were hospitalized for a bipolar manic episode, and they were follow up, and then later on develop an alcohol use disorder, they spend more time in an effective episode. They spend more time in a mixed episode, and they had more rapid cycling criteria. So this is also important data, and this also has been replicated in another study, this one by Pasciarotti, where two groups of patients with bipolar disorder were compared. Those whose symptoms were preceded by alcohol use disorder first, and other substance use disorders, and those where the bipolar disorder was not preceded. So, in other words, it happened first, before the beginning of the substance use disorder. And again, this is large numbers, 145 people with substance use and bipolar disorder, and 144 people who did not have any substance use and bipolar disorder. So the group with no substance use preceding the onset of the bipolar disorder had higher number of hypomanic and depressive symptoms. So once again, something happens when people have bipolar disorder first and later on develop an alcohol use disorder. This is an interesting study done in 2017 by Azorin, and this group included or measured what they call, what is known in the bipolar disorder literature as a temperament. So, the temperament is kind of like a biological signature of people's traits that can inform us. Perhaps there are some studies happening where we don't know if some of these people with those temperaments can be more prone to have bipolar disorder or not. So, what this group did is a logistic regression in 70 patients where alcohol use disorder had preceded the onset of bipolar disorder, and in the rest of the sample, that it was more than 500 people, bipolar disorder had preceded the onset of alcohol use disorder. So, they were able to differentiate two types of groups. So, when the alcohol use disorder happened first, they had a higher prevalence of anxiety disorders, irritable temperament, and comorbid sedative use and depressive polarity. So, they concluded it is like an irritable temperament, maybe associated with conflicts with the environment, could lead to the use of alcohol and sedatives to reduce the stress. However, in the other group, higher levels of hyperthymic temperament maybe could facilitate the use of stimulants, and those people were predisposed to have the first manic episode. So, this is just one study, and it's interesting to know if different temperaments could explain also some of the associations between alcohol use disorder first or alcohol use disorder later. So, I would like to briefly mention the studies done in adolescent population, because that can also be very informative. The first one is the course and outcome of bipolar youth, or COBI, a study that it was, it is a long-term naturalistic study done in hundreds of children and adolescents with bipolar. It is led by Dr. Bill Maher at the University of Pittsburgh, and this study followed up, in this case, 160 children with bipolar type 1, 2, or NOS, and they did not have a substance use disorder at intake, and they were followed up for an average of two years. It's important to know that one-third, which to me is huge, of these children develop a substance use disorder only after two years of follow-up, and it was mainly alcohol or cannabis use disorder. The incidents they found similar in bipolar type 1 or 2, in this case, this is different than the data that I presented before, so maybe adolescents with bipolar disorder might represent a different group, and they found that they did another multivariate regression, and they found that having a lifetime prevalence of oppositional defiant disorder, panic disorder, family history of substance use disorder, and low family cohesiveness were the main predictors for developing a substance use disorder, up to the point where 50% of the children having three or more of these risk factors developed a substance use disorder. Similar data have been also found in a more recent study done in 2016 by Willans, and this is another study where, in this case, it's a case-controlled, family-based study of adolescents with 105 and without 88 bipolar disorder at baseline and at five-year follow-up, and so there were different groups, and what they found is that almost 50% of the subjects with bipolar disorder developed an alcohol use or a substance use disorder compared to controls, and the risk for severe alcohol use disorder was five times higher in children with bipolar after adjusting for socio-economical factors. So, this is the last slide of the section two, and the question is, why does it matter? What are the consequences of having both bipolar disorder and morbid with alcohol use disorder? Well, this is the summary of the studies that I have presented, but the consequences of having the comorbidity is that people with this comorbidity had higher rates of mixed mania, more rapid cycling, increased severity of manic and depressed symptoms, higher levels of suicidality, as shown in different studies that I am now presenting here, more aggression. The STEP-BD found earlier age of onset of bipolar disorder when the comorbidity is present. They also had more suicide attempts, poorer functional outcomes, poor adherence, and finally, another study found higher risk of depressive relapse. So, the conclusion is that comorbid alcohol and bipolar disorder happen more often in men than women or almost double the prevalence in men versus women. Bipolar type 1 and alcohol use disorder is more prevalent, also almost double than bipolar type 2 and alcohol use disorder, and also, they might have a worse course. Adolescents with bipolar disorder are at very high risk for developing a substance use disorder, almost 30 to 50 percent. Bipolar and alcohol use disorder is more severe than alcohol use disorder first and bipolar disorder second, and when the comorbidity happens, there is a more mixed, more rapid cycling episodes, more suicidality, aggression, and less functioning and adherence to treatment. So, let's now talk briefly about why this comorbidity happened combined, and I entitled this section chicken, egg, or something else, and I'm not going to find the answer to that, but I'm going to present you a first classical hypothesis that they talk about this comorbidity, and the classical hypothesis use of phenomenological characteristics to explain this comorbidity. For example, we know that some symptoms of bipolar disorder, such as an increase in impulsivity in mania, they could lead to an increase in alcohol and other drugs use. We also know the self-medication hypothesis, which explains that the use of alcohol, which is said at the financiality, as we know, could help to improve some of the bipolar disorder symptoms. For example, insomnia and anxiety happen very often, and they could be improved, perhaps only in the short term with the use of alcohol, or the depressive symptoms, thanks to the euphoric effects of alcohol, could also improve. So, if this is the case, if we accept the self-medication hypothesis, then treating and correcting the bipolar disorder could lead to the almost automatic treatment of alcohol use disorder, but the inverse hypothesis postulates the opposite, and it postulates that the neurotoxic and destabilizing effects of alcohol, in this case in the brain, could lead to the onset of bipolar disorder only in some predisposed individuals, and if we take into account this hypothesis, then treating alcohol use disorder could probably prevent the onset of bipolar disorder. There is a third hypothesis, and it's that both share common risk factors, such as genetic, in a neurocircuitry level, or developmental problems. However, I think we need to be pragmatic here, and independently of the hypothesis that we are considering, and in lieu of the treatment, we need to consider the following options. So, I think it's important to point that, number one, if we are talking about different entities that go together, or a true comorbidity, what we are going to need to use is a combined treatment for A and B at the same time. So, A could be bipolar disorder, and B, alcohol use disorder. However, if we, instead, think that the combination of alcohol and bipolar maybe produces a third entity that I called C here, so then what we need to find is a unique treatment for this, maybe, alcohol disorder, so the combination of alcohol and bipolar. On the other side, we could also conceptualize this comorbidity as different expressions of the same problem. Then, the treatments that we will use are partial treatments, unless we are able to find some uniqueness to this comorbidity. So, what do we know? What we know is that the reality is more complex, or, in other words, the comorbidity might be unique for every patient. That's not surprising, because this is a complex comorbid presentation, so there is going to be some patients that we are going to find in our clinical, regular clinical care, who may be drinking alcohol only in certain phases of the bipolar disorder. This could be more in line with a self-medication hypothesis. However, we could also find other patients who might manifest the disorders as true and independent comorbidity, and both of them, we could say, take their own course and are happening together at the same time or in independent courses. What we know is that, for sure, the association does not happen by chance, and this is based on the family histories and epidemiological studies that I talked about before. We also know that if bipolar disorder occurs in adolescents, there is an increased risk for alcohol and other substance use disorders, and we have been able to identify a subgroup where, if bipolar disorder happens before alcohol, they have a worse course, as we explained earlier. So, I wanted just to finish this section explaining and presenting a concept that is called neuroprogression in bipolar disorder, and I would like to throw the hypothesis out there that perhaps, because of the combination of both entities, we're going to be dealing more frequently with a worse manifestation of these phenomena. So, I took this figure from this review paper from 2021 to explain what is neuroprogression in bipolar disorder. So, we know that cross-sectional clinical syndromes of mania, hypomania, and depression, they might have similar presentations among patients. That's why we are unable to many times classify those patients only in a cross-sectional way when they are presenting to us. However, is the longitudinal illness progression where these differences, it starts to become apparent, and some people do worse and some people do better. So, bipolar disorder has been associated with significant neurocognitive deficits across all motor states, depressed, mania, but also even in euthymia. So, this dysfunction that I am talking about, this neurocognitive and also social dysfunction, seems to be related to the severity of the disease, but also to the presence of psychotic symptoms, to a longer duration of the illness, and to higher number of manic episodes. So, in other words, repeated episodes of mania, especially when they are accompanied by psychotic features, that could lead to neurocognitive decline, and it's hypothesized that these individuals then develop what they call, the authors call, a neurobiological scar and also an emotional and psychosocial scar. So, there is a progressive deterioration in both clinical and cognitive domains, and what I wanted to connect is this neuroprogression hypothesis with the progression of what George Koop described in the case of addiction. So, this figure represents what happens, explained by George Koop, who also used other hypotheses from the early 70s and 80s by Solomon, and he described a stage in the addiction process that is known as the withdrawal negative effect. So, he presented what he called the neurocircuitry model of addiction, and one of the stages of this neurocircuitry, in this neurocircuitry model, is what he calls the withdrawal negative effect, and so what happens is, as you can see here, that the use of a drug produces maybe an elevation in mood, in this case represented by the wave A, but there is also mechanisms compensatory by the body, by the stress systems, that try to regulate this and produce a homeostatic mechanism, and try to get into the homeostasis equilibrium. So, the problem is that the progressive use of drugs leads to compensatory changes in the brain by these stress systems that George Koop talked about, such as catecholamines and stress systems like the corticotropin releasing factor. So, the progressive use of drugs leads to different levels of equilibrium, different levels that are called allostatic points, and what happens is that these changes represent or express themselves when the drug is not present, and that leads to all of the negative dysphoria that people suffer when they are in abstinence from the use of drugs. So, this concept of leading to progressive allostatic state and to progressive allostatic points is, to me, very similar to the concept of neuroprogression that I presented before. So, what happens is that the combination of both alcohol and bipolar disorder could lead to this overload in the brain. So, there is a break in some, there could be a break in some emotional and motivational regulatory systems in the brain, and this is expressed in this picture by a tree that, in this case, represents the brain that has been broken by extreme wind forces that could represent the combination of both drugs and chronic use of the stress systems. And by the way, I chose this image in reference to one book called Neuroprogression and Staging Bipolar Disorder, published by international leaders in the field. I'm providing here this table that you can download, and of course, please do not pay too much attention to what it says here. You can download it and pay more attention later if you are interested, but those of you who are more interested in this matter, it shows the most important contributed authors in the concept of neuroprogression. You are going to see that some authors pay more attention to the presence of the severity of the psychotic symptoms and the recurrences. Some other authors are paying more attention to the presence of cognitive symptoms in the inter-episodic periods, and some other ones are going to be talking more about the difference between bipolar or spectrum, classic bipolar disorder or the spectrum bipolar disorder. So, this is something for those of you who are interested. Finally, this is the last slide of the section 3. I think that it's important to know that more than an academic discussion here, ultimately, the idea is to get better individualized treatments, and this is in line with the goals of the National Institute of Health to move towards a more precise and individualized form of medicine. So, these authors from this review paper from 2018 differentiated a DSM and ICD form of practice medicine, and this is what we do now, where every patient with bipolar disorder would receive a standardized and consensus treatment. But we could move forward and get into a staged model of practice of medicine, where the treatment in this case will be based on the stage of disease of the patient, and even further into a precision staging model of medicine, where even more information and getting all of these omics characteristics that people talk about now, genomics, epigenomics, could lead to a more and more individualized form of treatment. So, the conclusions of section 3 is that it is important how we conceptualize this comorbidity, because it could influence the treatment. Bipolar disorder can be presented in classical presentations, but also in the spectrum of bipolar, and if we add alcohol use disorder on the combination, there is going to be a lot of variability in every patient, and of course, every patient is unique. However, we might be able to categorize in the future patients into groups, and that will lead us to offer more personalized treatment. Let's want to move now to section 4, which is treatment of bipolar and alcohol use disorder, and I picked these beautiful paintings by Van Gogh, that there are some reports that say that he has bipolar disorder or he has problems with alcohol, but independently of that, he was a genius. So, what are the principles that I created here that I think are very important for us, for clinicians, seeing patients in our regular clinical care? So, based on the information that I have presented earlier, based on the complexity that I have been trying to show to all of you, I have created some principles that I think are important to follow, and I think that following these principles could provide better care for patients with bipolar and alcohol use disorder. So, some authors talk about an integrated model of care done by the same treatment team. I think that this would be very important, because it would allow us to avoid the compartmentalization and allow the treatment team to have a wider perspective of the relationships between these two problems. So, it's important that this both, this comorbidity could be treated by the same people, and this is also convenient for patients, because that will also save them more visits, and perhaps that would even improve follow-ups and engagement, and as I discussed in Section 1, only 12% of people with serious mental illness and comorbid substance abuse receive treatment in a specialized center. It's important to know that these patients are going to have more medical comorbidities, so it's important to have a good care, a good combination of care between primary and specialty care, a good integration. I think that it's also important for us to know that the acute inpatient care can be needed more often. Why? Because we are going to have more decompensations from the bipolar perspective, so people who are in a severe mania, who are suffering from psychotic features, or who are having depression with cesarean ideation might need to be hospitalized, but also people might need to be hospitalized for medical management of withdrawal symptoms, so the combination of both might lead to have more acute inpatient care. It's important to follow also this principle that I'm presenting here, which is that we have to consider adding psychosocial treatment as soon as possible, and I think that involving the family could be very important, because family could represent a very, very good source of information, and they could help in engaging in treatment, and they could be very valuable informers to us. We are going to now just discuss some psychosocial treatments for this. There was an olaxioma and dual diagnosis that were telling us that we needed to treat first alcohol use disorder before treating bipolar disorder, or the same thing even with PTSD, but this is no longer the case. This has been proven to be wrong, and both disorders should be treated at the same time, and I wanted to show that and to discuss that despite the lack of studies, I'm going to show this now very briefly. I think it is important to add maintaining psychopharmacological treatment for alcohol use disorder soon, so medications like naltrexone, disulfir, and acamprosate. We are going to see that these are medications that are FDA-approved for alcohol use disorder. However, they have not been properly studied in this population. In my opinion, however, based on the safety and the benign profile of the side effects and on the consequences of alcohol use in both medical and psychiatric perspectives, I think that these medications should be considered in every case, depending on the profile, obviously, of every patient. And finally, the long-acting use of injectables like antipsychotics or naltrexone long-acting injectable maybe could improve the adherence and the outcomes in this population, but this has not been studied here. So, I'm going to briefly present in the next five minutes two different pharmacological approaches that have been followed. One of them, in the studies out there, a medication that is normally used in bipolar disorder has been tested to see if it helps not only the mood, but also alcohol outcomes. This is the case of lithium, valproate, and glutathione. Another approach is to see if a medication used in alcohol use disorder could be tested as an add-on to a regular bipolar disorder, could be helpful not only in alcohol, but also in mood symptoms, too. This is the case of naltrexone and acamprosate, and there are three psychotherapeutic approaches that have been studied, integrated group therapy, family-focused therapy in adolescents, and CBT and psychoeducation, only done in inpatient settings, and I'm just going to focus on the integrated group therapy for the sake of time. So, the first medication that I'm going to discuss is valproate. There is only, believe it or not, one study that was done in 2005 assessing the effects of valproate versus placebo in 59 bipolar type 1 patients and alcohol use disorder moderate and severe. In this case, a medication was added to the treatment as usual with lithium and psychosocial intervention, so the treatment was pretty much maximized, and these patients were still hospitalized when that happened, but they were also follow-up up to 24 weeks later, so this was a good study, and they found that the use of valproate did not make any difference in mood symptoms in the follow-up. However, patients receiving valproate had less heavy drinking days, defined as equal or more than four drinks per woman per day, or more or equal than five drinks per day per man. So, they also had less drinks per any heavy drinking day. And it's interesting that they found that a concentration of valproate in serum correlated with better alcohol outcomes. This is an interesting study. In the case of quetiapine, there are only three studies in the literature. The first one is a study in 115 outpatients with bipolar type 1 or 2, and they were assigned to quetiapine or placebo as an add-on to the treatment as usual with lithium or anticonvulsants, or even antidepressants. These patients were mostly depressed, and there were many of them not taking medications at that time. Quetiapine was found to improve depressive symptoms, but there was no alcohol changes. A multicenter study done in 360 bipolar type 1 and alcohol use disorder patients. In this case, quetiapine was used in 400 milligrams as an add-on to lithium or valproate, and that was compared versus placebo. Again, no changes in alcohol use was found. And 90 outpatients with bipolar 1 or 2 in a more recent study than in 2014, in this case depressed or mixed, 12 weeks of an add-on quetiapine extended release, 600 milligrams, which is a very, very considerate dose versus placebo. And again, no changes in alcohol use. What about naltrexone? So, in the case of naltrexone, the evidence is even smaller than the one that I just presented here. In the first study, naltrexone was added to the treatment with valproate, lithium, or antipsychotics, and also CBT in 50 outpatients with bipolar type 1 or bipolar type 2 for 12 weeks. It's important to point out that only 26 of these patients completed the treatment, so not a large proportion of the sample. They found that there was a trend, which is not surprising based on the number of people who completed the study, in any drinking day for the patients assigned to naltrexone, but they found a moderate effect size in alcohol cravings. So these are good news. There was, and this is also interesting, there was an improvement in liver enzymes in those patients assigned to naltrexone. This is important to highlight because a lot of clinicians out there are afraid of using naltrexone based on the possible hepatotoxic effects, especially people with alcohol use disorder, and this is important to point out that it could even improve the liver enzymes. There are two other open-label studies, small randomized studies, and there is finally a large VA-based study in 254 patients done by Dr. Petrakis, patients with serious mental illness and alcohol use disorder, and the study showed that both naltrexone or disulfiram, which is the active compound of underuse, they were both safe and effective in craving reduction. It's important to know that in this study, the results were not shown into a specific Axis 1 disorder, so I cannot talk about what happened in bipolar disorder, but at least in severe mental illness, which is the sample population, it was found that these medications can be used in a safe way. So, what about psychotherapy? This is the last slide of this section, section four, and there is a specific psychotherapy called integrated group therapy. This psychotherapy employs a CBT relapse prevention model, and it was specifically designed, as I said, for the treatment of this comorbidity. So, in this form of group therapy, the conductors of the groups emphasize similarities between relapse processes in substance use disorder and also bipolar disorder, because relapse happens in both, if it's the mood or if it's the drug use. So, there are two randomized clinical trials. The first one was done in 62 patients and 80% in bipolar type 1. They were also taking valproate, lithium, or both, and 60% of the sample had alcohol, but also drug use disorder combined. So, this is a more severe population than usual, and they were assigned to integrated group therapy versus regular group drug counseling. The treatment lasted 20 weeks, and the integrated group therapy, what they found is that they found less number of days of any substance use, mainly alcohol, but they didn't find any mood differences in both samples. The second randomized clinical trial was done by the same group in 2009, and it was a little modification of the original protocol in what they defined as community-friendly delivery, because in this case, the counselors offering the treatment did not have any previous training in CBT, and the delivery of treatment was 12 weeks instead of the 20 weeks studied earlier. So, this means that it could be easily translatable to regular clinical practice. In this case, integrated group therapy showed a trend with less days of substance use during follow-up, but also less mood episodes during treatment. So, this is good, and typical outcomes in these very complicated studies to conduct. So, what are the conclusions on section four? It's that there is an alarming lack of studies in psychopharmacological and psychosocial treatments. We only have data in valproate added to lithium, in naltrexone added to mood stabilizers, and on integrated group therapy. These are the positive data that we have found. Bisulfuran and naltrexone we know that are safe to use in population with serious mental illness, and ideally, the treatment should be provided, according to those principles that I showed before, in an integrated medical model of care, ideally in the same setting, with a good collaboration with primary care and specialty care, and having easy access to acute inpatient units. I know that this can be very difficult, especially for a lot of clinicians working in community mental health clinics. So, I think this reflects one of the possible difficulties and challenges of the system that we have. Finally, I also wanted to point out that early psychosocial treatment involving the family, ideally, should be offered, and I think, very importantly, the treatment of alcohol use disorder should be started as soon as possible. Let's now finish with section five, and I would just like to talk about the treatment. What's going on in the treatment in racial and ethnic underrepresented minorities? I think the presentation will be incomplete if we do not take into account the disparities in medicine, and not only in the diagnosis, but also in the treatment in this minority population. So, the first question that I wanted to show is the first message that I wanted to give, sorry, is that there is no research in bipolar and alcohol use disorder in minority population published in the literature. So, that's the first message, no absolute, nothing has been published. And the cultural influences are so important that in many cases, they could even be the main driving force into the treatment. For example, this study by Bromley and others in 2000, showed that in this sample of 87 people with severe mental illness in public mental health clinics in Los Angeles County, the people identified alcohol use disorder, the use of medications for alcohol use disorder as something negative that they needed to avoid. And why is that? Because that could interfere in their development of the self-control coping skills. So, they even thought that using medications for this is a bad thing, it's something that should be avoided. I want to present just two more slides, showing two examples of each of the separate comorbidities, because like I said, there is no studies done when the comorbidities are present together. The first slide that I wanted to discuss is what happens in the case of blacks and bipolar disorder? Well, there is no significant, despite that the ECA or the epidemiological catchment area did not find any significant differences in the rates of bipolar disorder among different groups. There has been consistent studies pointing out that bipolar disorder is being misdiagnosed in black population compared to white population. For example, a large 2004 VA study done in more than 130,000 people explored this relationship between ethnicity, symptom presentation, and diagnosis. And African Americans were four times as likely to have a schizophrenia diagnosis when compared to otherwise similar white Americans. And this is adjusting for potential demographic confounds. So, you can see what is going on and how important this is, what I am talking about. And not only in relation to diagnosis, there is a concerning bias, but also even in the treatment. This is a popular 2003 cross-sectional study done in 535 hospitalized individuals. These individuals had bipolar disorder. And this study confirmed, again, that African Americans in comparison to white patients were being prescribed, in this case, antipsychotic medications at a higher rate, 92% versus 62% of the sample. So, they are also not only being bipolar, so it's not only being misdiagnosed, but also mistreated. And because there shouldn't be a reason to use more antipsychotics in a sample that has been adjusted for severity and other socio-economical factors. A recent review done in 2018 concluded that non-biological, and that is what they call historic mistrust factors, could contribute to these health disparities. So, they talk about slavery, institutional racism, discrimination, poverty, and segregation as some of these factors. Now that I talk about what happens in bipolar disorder with this example, I want to talk about what happens with minorities in the case of alcohol use disorder or other substance use disorder. For example, a study done by Pinedo in 2019 concluded that Hispanics are less likely to complete substance abuse treatment. They are also more likely to underutilize treatment, and they are also more likely to perceive a lack of treatment efficacy. And not only in this small study, but there is a recent review of 24 studies done in Hispanic population, and this population has participated in the NIDAS clinical trial network. And the study, the review identified that these populations suffer from lower employment rates, problems with insurance, increased travel time to substance use disorder treatment, geographical inaccessibility, citizenship status problems, level of acculturation as some of the reasons why Hispanics are not only receiving worse care, but also they are being underrepresented in clinical trials. So if we are not even representing these populations in clinical trials, the medications and the psychotherapy that we are finding, where are we going to, are not being able to be generalizable to the whole population. It's only going to be generalizable to the majority. So I finished this presentation with a section in this, in section five, pointing out again that there is an alarming lack of research in racial and ethnic minority. This creates what I call an uncomfortable truth that the diagnosis and treatment of bipolar use disorder, not only alcohol, but substance use disorder in general is suboptimal in minority population. I think that there is a need of cultural competency training, and ideally the treatment of this population should be done by multi-minority teams that will be able to assess better, to treat better, and to perceive better the complexities. And honestly, it's also important to show that social determinants can actually be more powerful than biological determinants for the success of treatment in this very complex comorbid situation. Thank you so much for that presentation. It was just jam-packed with information that we can act on, and it was really interesting, and I loved the conclusions throughout, really helped me see where we need to be going. Before we shift into Q&A, I want to take a moment and let you know that SMI Advisor is accessible from your mobile device. Use the SMI Advisor app to access resources, education, and upcoming events, complete mental health rating scales, and even submit questions directly to our team of SMI experts. Download the app now at smiadvisor.org forward slash app. And I'll go to our questions now. So, do you have any thoughts or knowledge of studies on prevention of comorbid bipolar and AUDs? I don't. I did not find any studies there, and the only data is the data that I presented, which is that adolescents who already suffer from bipolar disorder are at very high risk for developing a substance use disorder. So, this is a special population where I think prevention intervention should be focused very intensively. I don't have any data about if the use of, perhaps in my own hypothesis, the use of early psychosocial interventions could lead to a diagnosis of this population, but I don't have any data there. Right. It sounds like, I mean, just from me following your talk today, that it seems especially critical to talk to these transitional age youth about alcohol use, especially if they're showing mood disorders, particularly bipolar disorder. Yes, that's very important. And the case that we know many times that in bipolar disorder, major depressive episodes tends to be the presenting episode in the majority of people. So, it is difficult for us to know if these people with depression are going to end up developing bipolar disorder or not. So, the efforts in prevention for the comorbidity should not only be focused in bipolar disorder in general, but even in first episode of depression on anyone. Right. One of the other questions is about sort of debunking the myth of treat one before the other, but rather to treat them at the same time. And I'm wondering if you can speak for a minute about how you talk with clients about treating them at the same time, sort of how do you do that? This is a difficult treatment, obviously. And I think that in my experience, the most successful outcomes come when patients trust us, obviously. So, having a good therapeutic relationship is going to be the main cornerstone to have these conversations. But very early when I meet patients, I try to present them and I try to talk to them. I present this idea of both bipolar and alcohol use disorder going waves, how they both potentiate and correlate to each other. And I explain to them that we need to treat both ideally at the same time. Now, it is also important that many people are going to present to the clinic in different stages of change. Some people are not going to be ready to get treatment for alcohol use disorder right away. So, I see in the long term relationship where things might hopefully change and hopefully get into a higher level of stage of change and accept treatment for alcohol use disorder. But there are people that are ready to be treated for both. And I do start treatment for both from a psychopharmacological perspective at the same time. When you look at the results from psychotherapies, what would you recommend, and which style of psychotherapy to start with someone who has comorbid bipolar disorder and SUD? Well, the reality is that the group psychotherapy that we talked about here before, the integrated group therapy, is not accessible mostly everywhere. So, sometimes it's more important to focus on starting a form of psychotherapy for the treatment of alcohol use disorder. If I had to pick, I would rather pick someone starting the treatment in a psychotherapeutic modality for alcohol use disorder at the same time that I am already prescribing a medication for what they call for maintenance. And maybe at the very beginning, I need to focus more on a pure pharmacological treatment approach for the treatment of bipolar disorder. So, it depends on how are they presenting to you? What am I going to be picking? Sometimes patients are in a stage or in a level of alcohol use that is so destabilized that they need to be hospitalized from a medical perspective in order for them to be safe to even continue the treatment. I can't focus on the treatment of bipolar disorder if the alcohol use is very much out of control and they are at risk of developing seizures or any other adverse outcomes. You know, one of the things that's so important for many clients is having hope that they can actually get better. And we're talking about two disorders that have a chronic waxing and waning course. And many people come forward and say, yeah, I've tried this before. It hasn't worked. Or I don't see myself ever getting better. How do you talk to someone and provide hope that they could actually become more stable and have a more full life? I always compliment the patient who is in front of me because they came to see me and that's a sign that they already want to get better in the treatment. And I also would tell the patient that we don't have any way to predict who is going to be doing better or who is going to be doing worse. And I tell them that I have seen in my regular clinical care people that I thought or they were doing very poorly. And many times, the course changes. Something clicks and people start to do better. So I think that obviously, if that's what I mentioned before about involvement with families, but the involvement of families will be a very important piece here because they are going to be almost caretakers in many of these. So I think it's a very important part to form good alliances with families, with patients, and present the data in a very honest way. I can't say how you are going to be doing. So I understand the level of suffering and frustration that many of them might be going through, but things can change. And in fact, for some people, things change and they do better. Thank you so much, Dr. Ballester. And thank you for audience members who wrote in today. If you have any further follow-up questions about this or any topic related to evidence-based care for serious mental illness, our clinical experts are available for online consultations. Any mental health clinicians can submit a question and receive a response from one of our SMI experts. Consultations are free and confidential. SMI Advisor is just one of many SAMHSA initiatives that are designed to help clinicians implement evidence-based care. We'd encourage you to explore the resources available on the Mental Health, Addiction, and Prevention TTCs, as well as the National Center of Excellence for Eating Disorders and the Suicide Prevention Resource Center. These initiatives cover a broad range of topics from school-based mental health through the opioid epidemic. To claim credit for participating in today's webinar, you'll need to have met the requisite attendance threshold for your profession. Verification of attendance may take up to five minutes. You'll then be able to select Next to advance and complete the program evaluation before claiming your credit. Please join us next week on July 29th as Dr. Crystal Glover with Rush University presents Diversity Among Persons Living with SMI, a focus on older adults. Again, this free webinar will be July 29th, 2021, from 3 to 4 Eastern Time. Thank you for joining us today, and thank you to our faculty presenter. Until next time, take care. you
Video Summary
In this video, Dr. Javier Ballester discusses the comorbidity of bipolar disorder and alcohol use disorder. He emphasizes the importance of treating both conditions simultaneously rather than treating one before the other. Dr. Ballester discusses the epidemiology of the comorbidity and its impact on clinical outcomes. He also presents data on the prevalence and treatment of the comorbidity in minority populations, highlighting the disparities that exist. In terms of treatment, Dr. Ballester discusses psychopharmacological options such as valproate and naltrexone, as well as psychotherapeutic approaches like integrated group therapy. He underscores the need for an integrated model of care and the importance of involving families in the treatment process. Dr. Ballester also discusses the need for more research in the field, particularly in minority populations, and emphasizes the importance of cultural competency in providing effective care.
Keywords
bipolar disorder
alcohol use disorder
comorbidity
treatment
epidemiology
minority populations
psychopharmacological options
integrated group therapy
research
cultural competency
Funding for SMI Adviser was made possible by Grant No. SM080818 from SAMHSA of the U.S. Department of Health and Human Services (HHS). The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement by, SAMHSA/HHS or the U.S. Government.
×
Please select your language
1
English