Hello, I'm very glad to speak to this distinguished group to discuss what I think is a very important issue these days, and that's the concept of ethno-psychopharmacology, recognizing that there are individual variations in terms of response and outcomes in pharmacology. And the objectives of this will be a group of distinguished speakers who recognize the biological and social determinants, that there are, in fact, ethnic differences in terms of drug metabolism, to recognize that there's special care that must be taken to side effect profiles when different ethnic groups are considered, and also to recognize the disparity of minority groups in relationship to access to care, stigma involved in seeking care, and psychopharmacological treatment. And with that, I will now turn to our first speaker, Dr. Napoleon Higgins. Thank you, Dr. Lawson, and I am so appreciative of being invited to be a part of this talk. The objectives of what we're going to talk about today are to go over the biological and social determinants. So often, when we're looking at patients and outcomes, it's more than just what prescription we wrote for them, but the biological processes that occur with the body, so far as what the body does to the drug, and then also what the drug does to the body. But beyond that, there are also still other social determinants that we must take into consideration when we're looking at efficacy for the medication, as well as what we're trying to treat. So everyone is about the same, but realize that all of us can be very different in how we respond to the medication, and even looking at the issues of how our metabolism works. So special care must be given into consideration when looking at efficacy of certain medications, side effect profiles. All of this has to come together in order to make sure that we're prescribing safely and correctly and having the best outcomes for our patients. Understanding that there could be many disparities when it comes to minority groups in relation to care, seeking care, and the medications that we actually pick in order to use for the population. So understand this, though. We don't want to lump everyone into one group. Understanding that everyone has their own biological DNA. And then also, we have to take into account that just because you look like this physically on the outside does not mean that you have the same biology. You can't stereotype and say a person has the same biology on the inside. So even though we can have, we are very similar, you can have a lot of differences even within different populations. So we must distinguish the difference between biologic and ethnic determinants when considering development in prescribing medications. So key considerations are the biological factors and the pharmacokinetics, as well as the pharmacodynamics of how the medication is going to work inside of the body. Also, you have to consider the comorbidities and other issues that an individual has when it comes to treating their mental health care, as well as their physical health care, and the interplay between the diagnosis and the medications that we're using, as well as the person's own individual genetic differences as well. Social factors such as access to care are very important. Stigma suffered by minority groups so far, stigma about illness, and also stigma and racial factors that go into decision-making also impacts outcomes amongst various ethnic groups. So there are disparities. So often, we may lump individuals into a type of person who we say that the medication works for. Obviously, as you know, America, the majority population is white, but the dynamics of the population are changing. But when you look at disparities in research, you're looking so often at medications that came out 20, 30, 50 years ago, even more, that we're still using today. Understanding that, a lot of those studies were done in white males. So having to take into consideration women, people of other ethnic differences, people who eat different foods, other biological processes go into play that were not necessarily researched when these medications first came out. So we need a clearer picture on how these different medications work in this population. Understanding that we have seen where you have protocols for heart failure, so far as with blacks, and medications for hypertension, that has shown that, well, these medications work well in black people. Well, the question becomes, are there biological differences and ethnic differences, so far as DNA? Are there differences in the type of foods that people eat? Looking at food deserts, things of that sort, change what type of foods people eat. And you may be looking at a medication that could be working despite those other issues in this population, not to mention the stresses of racism that can occur in black populations. And I would say to myself, as I question, do the other medications not work? Or is it more so that this medication works despite that? When you look at elevated levels of hypertension in black people in America, there are many theories of why that occurred, so far as the middle passage, and being able to collect salt, and be able to have genetic differences, survivability of the issue of the slave trade. But the other side of that is, why don't you see that same high blood pressure in people in the Caribbean, who would have come over through similar measures? So we have to look at all of these things to determine how the medication may work, and look at outcomes for our individual patients. So with doing that, I want to talk about Project IMPACT, so far as trying to improve the validity of our clinical trials, and to try to make sure that we have more patients of ethnic, more ethnic diversity in the patient populations that we're studying. As a person who does some clinical trials, you know, the thing is that a lot of things, you find that with black, say, for example, black doctors are more likely to see a higher volume of black patients. So the need to increase that diversity so that we can get more ethnic groups in is going to be important. We need to support the development, understanding that a lot of universities may, you know, I could think of, you know, a university where I went to, that was majority white, primarily white, in so far as the university, but there seemed to be a disconnect between the community that was majority black that was on the other side of the street. So understanding that the need to be able to support other groups and other people, the need to be able to support smaller private practices, or even county practices to be able to get more of that overall population is going to be important. So the project IMPACT was created in 1993 by National Medical Association, where I first got my feet wet with understanding clinical trials and getting a certification in order to do so, and that has built me to where I am now. So we need to rectify the issue of not having valid data with diverse populations of all colors, of all groups, of all socioeconomics, because all of that goes into whether or not a medication may be efficacious or not. Thank you. And now I'm going to discuss drug metabolism and other related issues to build on what Dr. Higgins has just mentioned. First of all, different mechanisms underlie how drugs are metabolized. We now begin to appreciate in recent years is that metabolism can be different in different populations, because of protein binding, enzyme inhibition, and inductive mechanism. Protein binding, enzyme inhibition, induction, genetic polymorphism, or even duplication and coding regions of these enzymes, both psychotropic and non-psychotropic medications may be absorbed, metabolized, or excreted at different rates in different people. Now, one of the well-known phenomena is the alcohol flesh reaction, which is a result of acetaldehyde dehydrogenase deficiency that occurs in many folks of East Asian ancestry, which causes acetaldehyde accumulation after alcohol injection in some East Asians. And by the way, a similar mechanism may explain a very small intolerance of alcohol in terms of African-Americans, which may explain why African, especially African-American females are less likely to be alcohol dependent. Promethane-induced hemanalysis based on G6PD deficiency is also found in African-Americans. And also, Southeast Asian population, carbamazepine-induced SGS-10 is strongly associated with the HLA-B1-502 allele. And I might add also that what we find among African-Americans is that many African-Americans tend to be at risk for carbamazepine agranulocytosis. Now, among psychotrophic medications, we find that one of the important cytochrome P450 subsets for hepatic metabolism is the CYP2D6. It is known to have ethnic variation. There's some of the other enzymes that do not have ethnic variation, but CYP2D6 quite very much has so. And what we found is that some people are what we call poor metabolizers. They have two inactive or deficient alleles, which can lead to higher levels of a drug and more severe adverse effects. On the other hand, there's another group that is ultra-rapid metabolism caused by three or more active alleles, which will cause low levels and may falsely represent treatment resistant psychiatric disease. What we find is that if you look at people of color, that we actually find both cases that among the Ethiopian population, they have active genes for CYP2D6 compared to 15% of Arabs and 1% or 2% of other Black, Asian, or European populations. In contrast, 7.7% of occasions are poor metabolizers and on 25% had mutant alleles. So, if you decide to use skin color or the traditional racial differences, you get in difficulty because clearly we find that some groups, such as those who may have strong Ethiopian representation in the population, may be rapid metabolizers and thus, if you give the standard dosing of a medication, you may find that it will not work. On the other hand, also, people of color who are given such drugs may actually be overdosed because they may have poor metabolizers, even though they may have the same skin color defined legally in terms of how we use race in characterization of patient populations. So, it's extremely important to recognize that this kind of variation can occur across the traditional racial groups. We know that psychotropic drugs, such as risperidone, hamiperidone, thiazine, and nonsicotine, and SSRIs may be metabolized differently, especially if you use in other drugs that are metabolized with CYP2D6. That's tamoxifen and SSRIs, for example. And we also recognize that some of these agents may react differently. One of the interesting polymorphisms is the serotonin transporter gene. Serotonin transporter gene is well known in terms of being important in depression, and in several large studies, we found that the transporter gene actually helps to predict antidepressant response. So, the serotonin transporter genes involve serotonin reuptake, and we can have variations in insertion and deletions, and we know that the short-arm deletion has been also shown to be predictable, whether or not folks are tolerant of adverse events, whereas the long-arm offers prediction. And what we also find is that the basal activity of the long-arm is twice, the short-arm and L, and the long-arm tends to have better response to SSRIs. In a large study of antidepressant response, it was found, for example, that African-Americans many times tend to show more robust response to SSRIs, precisely because of representation of the long-arm. East and South Asians are rarely homogenous long-arm, and more research has to be done to see if there is an association between this and antidepressant efficacy or baseline mood. There's also healthy variations in diet, and we find that diet does impact pharmaceutical efficacy. Cruciferous vegetables, broccoli, cauliflower, cabbage, CYP450 induces increased metabolism. Smoked food used charcoal to cook induces CYP450. Corn, carrots, citrus fruit, grapefruit juice, CYP450 inhibitors, and well-known that grapefruit juice can have clinical significance if one uses certain SSRIs. Indian spices used in South Asian cuisines, such as cinnamon, cardamom, black pepper, inhibit CYP450, and coffee is a CYP450 inhibitor as well. We're now actively doing work showing that these variations in terms of spices not only affect activity in terms of metabolism, but it also affects olfaction and taste to the extent that it can affect preference for certain kinds of behaviors, such as drugs of abuse. I will now go to our next speaker. Thank you, Dr. Lawson. Now, what I'd like to share is just a brief survey of some of the research out there that illuminates some of the things that we've discussed in terms of variations with medications in different populations. I'll start with neuroleptics. They say that the average prescribed therapeutic dose of neuroleptics varied greatly from country to country. Patients from non-Western countries like Turkey, India, China, Malaysia, Indonesia, all show clinically improved symptoms at much lower average doses of neuroleptics when compared to Europeans and Americans. One study, one drug in particular is haloperidol. The CYP2D6, as we all know, as mentioned before, has several polymorphisms, but one in particular is the 1-0 allele that causes decreased CYP2D6 activity and is present in East Asians at a 50% frequency, which is pretty significant if you think about it. That's essentially saying that half of East Asian populations have this polymorphism. A study that looked at the effects of the 1-0 allele on steady state plasma concentrations of haloperidol and reduced haloperidol showed that the mean steady state concentration was significantly higher in patients with 1-0 allele polymorphism than those without it. And when they looked at it further, they found that the mean steady state of reduced haloperidol was significantly higher in patients with not just one, but even higher than the one with two alleles for that polymorphism. Again, the study suggests that the 1-0 allele plays an important role in controlling the steady state of both haloperidol and reduced doses of haloperidol, especially in Asian subjects. I would like to say and add that, as we know, this is not just true of haloperidol, but again, all medications that essentially go to 2D6, which as Dr. Lawson has mentioned, there's more than 30 that we've identified. And this is also not just a realm unique to psychiatry, but several drugs, as mentioned before, such as pain medications like oxycodone, and more significantly, there's a robust amount of research that shows its significance in cancer drugs like tamoxifen. Tamoxifen is a prodrug that needs to get converted to its active drug through the 2D6 mechanism. And what they found is that in Chinese populations, it's more difficult to get higher. There are studies that show it's difficult to get the higher concentration of the actin metabolite due to suggested mechanisms such as this polymorphism of 2D6. But coming back to haloperidol, there's another study showed that by Potkin reported that after receiving 0.4 milligrams of haloperidol per kilogram body weight daily for six weeks, the plasma haloperidol levels of Chinese schizophrenic patients were 52% higher than U.S. non-Asian schizophrenic patients. Another study by Leonard Pollan administered a small dose of haloperidol in 22 Asians and 12 Caucasian normal volunteer subjects, and again, found that significantly higher serum haloperidol levels in Asians. As you would suspect, corresponding to that, the prolactin response to the haloperidol challenge was also significantly more prominent in these Asian subjects than Caucasians. So again, it's not just the medications themselves, but we have to consider the ramifications of the side effects of these higher doses of the medications that we're administering also. So it's not just the medications, but also the side effects that we need to consider. Switching gears to another medication of the TCAs or tricyclic antidepressants, tricyclic antidepressants are largely metabolized by the CYP2C19 enzyme. Other medications like diazepam, citalopram, or escitalopram are also metabolized by that CYP enzyme, but there's also some minor metabolism by most SSRIs. So essentially this is by TCAs, but largely most of the SSRIs go through some metabolism by the CYP2C19. Well, in regards to the polymorphisms of the 2C19, there's the 2 allele and then the allele number 3 are two unique polymorphisms leading to poor metabolism. And what's interesting is that 2C19-3 allele is found most exclusively in East Asians. So the presence of the CYP2C19-2 allele leads to an aberrant splice site. So it's a missense mutation. And then the CYP2C19 3 allele is a nonsense mutation, which corresponds to a premature stock codon. Now, as we all know from biochemistry, anytime you have any aberration to the enzyme or the figurative confirmation, you're not gonna have an effective enzyme. So either one of those are gonna, allele polymorphisms are gonna lead to a less than functional metabolism. What we found is that because of the presence of these polymorphisms, we find that extensive metabolizers are typically individuals who have two wild-type or what we consider normal functional alleles. We find intermediate metabolizers in two different forms. Either you have two reduced functional alleles, either allele two or allele three of the CYP2C19 allele, or you have one functional or wild-type allele, and then one non-functional or null allele. And of course, poor metabolizers are gonna be individuals with two non-functional alleles. Now, what this all comes into is that 15 to 30% of East Asians, including Chinese, Japanese, Korean, show polymorphisms with CYP2C19, whereas only three to 5% of Caucasians are polymorphic. So again, another variation in terms of how these polymorphisms affect different populations. Again, further studies by Ziegler-Briggs treated 65 patients, black and white, undergoing treatment for the depression with either amitriptyline hypochlorite or nortriptyline hypochlorite. What they found was that there was no difference in the rate of demethylization of amitriptyline to nortriptyline, or steady-state tricyclic levels in the amitriptyline-treated groups based on race. However, in the nortriptyline-treated group, black patients had significantly higher, 50%, nortriptyline plasma levels than the white patients. This may explain that faster clinical response to tricyclic treatment by blacks, but although it's spun in a positive way, this also puts them at increased risk for overdose, if not considering these things fully. Also, the decreased rates of nortriptyline metabolism in blacks may result in increased side effects and treatment failure if the therapeutic plasma range is exceeded. Again, that's not just in terms of treatment response, but also the side effects that may be related to tricyclic antidepressant levels. Similarly, another study found that black patients recovering from an overdose of tricyclics had higher plasma levels than their observed Caucasian counterparts. In one study, five of 23 black patients found that tricyclic antidepressants developed delirium compared to similar effects in only five of the 102 white patients. This difference was independent of age and plasma drug levels, so again, it's not even specific to just the levels, but again, as we talked about before, the unique pharmacodynamics and the kinetics of the individual patients showing that based on population, there may be variations that we're not even aware of yet. So again, another opportunity for research and further development and innovation there. Another drug that we found some research in regards is lithium. Bipolar patients in Japan responded to lower doses of lithium with corresponding low therapeutic blood levels of 0.4 to 0.8. Taiwanese bipolar patients with lithium levels were maintained between 0.5 and 0.8, achieved better clinical results than those with lithium levels outside this range. Again, two unique, different geographic areas, but with similar ethnic racial origins showing different response to different levels in medication. So studies consistently indicate that East Asian bipolar patients respond clinically to lower lithium levels compared to those in Caucasians. Now, there's definitely different mechanisms for why this may be. There hasn't been a unanimous consensus on why that is, but one suggested one is the GADLI gene polymorphism that has been implicated with lithium metabolism in Asian populations. However, again, there hasn't been a consensus as most studies have been mixed. There's other explanations that suggest that it could be dietary or it could be cultural, a variety of different things. As we know, lithium levels are affected by our diet, and it's also fairly well accepted that Asian countries have a lower sodium intake, which may cause a more therapeutic range of the lithium even when they're at lower levels. So again, another opportunity for more research to suggest mechanisms, but always something to consider when considering treating our patients. At this time, I'll turn it over to Dr. Bailey. Yes, thank you very much. I think that today's discussions are certainly very timely for a number of reasons. Now, Lisa, which is the basic idea that we want to make sure we can treat our patients better, and having information for all of us for a variety of diverse patients, diverse in race, ethnicity, diverse in their dietary mechanisms, diverse in, I think, their own individual capacity to metabolize meds, if you will, all clearly play a role in our medication determination for us as psychiatrists, as well as they can play a role in how we actually determine why individuals may struggle, some may struggle to respond to our treatments, let alone to show any response or even get all the way to remission. I got to begin my comments today with an axiom that I learned early in training. The reality is one reason many African-American patients who often, early in my career, were being challenged for the construct that they were frequently medication non-compliant, one reason that that was the case was this inability of their officer to metabolize that, as was described, I think, I believe by all of my co-panelists here, to metabolize that cytochrome P450 2D6. And so many of the older antipsychotic medications, especially the butyrophenones like Haldol, if you will, or the lymphatic treatments like Thorazine or Chlorpromazine required 2D6 for metabolism. So many medicines were not metabolized by these groups. The individuals very often would have side effects. They stopped taking the medication and they'd be blamed for it and criticized very often that was used against them in many settings. So learning that early in my career made it very clear, very apparent to me that we all need to be very mindful of these issues, discuss them, I think, pretty clearly, pretty regularly, but also think to find ways to integrate both internally and externally throughout our processes of these strategies so that patients that have an overall better chance for clinical care and overall clinical improvement. My first slide today addresses comorbidity. So what happens when an individual has more than one medical problem? Often we describe co-occurring illness within the vernacular as having more than one psychiatric diagnosis. ADHD, for example, is the most common co-occurring psychiatric illness. About 40% of the time, two out of five individuals with ADHD will also independently meet criteria for a different primary psychiatric or access one diagnosis. But in medicine, we see this issue as well when individuals have a greater likelihood of having more than one medical complication when they have a psychiatric issue. Our bullet point points out that certain ethnic minority individuals, including African-Americans, Hispanics, and Asians, often suffer increased rates of obesity or diabetes related to this illness. Others that's very interesting, Dr. Cho made the point that cinnamon was one of the dietary vectors that actually plays a role in these issues in some settings, it's been used as a frequent spice in certain Asian or Far Eastern cultures that actually may limit hyperglycemia or diabetes in some settings. So clearly being mindful that the comorbidity issue when a person has really more than one primary concern can come into play, although some of the dietary measures like cinnamon may actually be helpful in limiting those overall degrees of risk. A second bullet points out that we must employ caution and discretion when it's prescribing psychotropic drugs such as metabolic syndrome, inducing antipsychotic medication in predisposed populations. And I think I spent a decade of my career, as many of us have, addressing the construct, and really I think many would argue to be a failed initial ideology that the medications, especially the era, I think, of medications in the category of new generation atypical medications caused hyperglycemia or etiologically caused diabetes. I think over time, quite a bit of work was put in to show that the medications very often can have a role to play. Some individuals, because of their own internal structure and how they metabolize meds may be predisposed to a greater degree of risk. But the big issue particularly I think is the idea that how we manage meds as prescribing psychiatrists and physicians of patients who have these particular vulnerabilities, I think speaks volumes for whether or not a particular patient may actually be at such a high risk when you include the medications that we offer to treat the primary psychotic illness and whether or not they are managing their diet and their exercise and their behavioral modification interventions to limit the overall risk of the adverse outcome of developing a hyperglycemia latent concern, even AODM or diabetes. So this point that we must employ caution as psychiatrists is key. And I think the term discretion is not used incidentally. It really is our responsibility. And I point that out to remind myself to say that I make the point to my students and trainees pretty regularly and I remind myself in a daily basis working at a inpatient county funded inner city energy care hospital in Los Angeles now that patients have come to me with primary psychiatric illnesses that can be fatal. And although they release pretty substantive morbidity or disease and impairment, inability to work and live independently or maintain relationships of family and friends and otherwise, but they also can have early mortality. So it's my responsibility to keep that in mind and to be mindful that the primary responsibility of the psychiatrist, especially in the era where we may be the only person, not only the only licensed prescribing physician, but the only clinician that takes care of a psychiatric patient that has the capacity using adequate and optimized psychopharmacology to treat patients in a fashion that may actually prevent them from having the ultimate adverse outcome or early mortality. So we must use discretion. I mean, we must prioritize medications that I can actually manage or treat the primary problem. But in the construct, we must also, I think, consider consistently what are the metabolic risks and how can we balance them? I was very pleased as many of us have been to appreciate that when co-abilities are in play, there are meds that we can use somewhat in the historical psychiatric arena, some outside psychiatry that we actually bring to bear in this discussion that can have remarkable value. I don't show it on the slide, but I think the medication Topiramate or Topamax has been shown to be as effective as any in managing these dual problems of mood lability, having an indication independently for mood lability concerns, such as manic symptoms, or even a diagnosis of bipolar disorder, as well as managing the potential issues regarding risk of a hyperglycemia or a iatrogenic or medication-induced weight gain in individuals who are likely to receive meds that come from the category of atypicals, where these issues are a lot more likely to occur. I should also argue that all atypicals are not alike. We often think that the meds that fall in the category of pains, Clozareal or Clozapine or Cortipine or Seroquel and Olanzapine or Zyprexum have been many that have been shown in psychiatry to be much more likely to lead to these difficulties and create a greater, I think, indication for a greater consideration for us as psychiatrists to think about the metabolic risk and particularly engage in actions, including medication augmentation strategies like the use of Topiramate to manage and minimize the risk of metabolic syndrome. Then there are social, cultural, economic differences. On the next slide, ineptic populations are clear. I think my colleagues today have made the point very, very clear that you see this across a variety of populations. Bill Lawson talked about the Ethiopian population and the 30% greater risk of alteration at Tytochrome P452D6. I think Dan Cho spoke about how these Asian populations have greater vulnerability at 2C19. I've often thought, in addition to the fact that in psychiatry patients, we often see this very high rate of smoking and cigarette or nicotine dependence, and we recognize that those same so-called pains, olanzapine and cortiopine and clozapine that I mentioned earlier, have increased metabolism when a person actually smokes cigarettes or just nicotine, because it induces the metabolism at Tytochrome P451A2. So these other issues that are social, cultural, such as a greater risk of smoking in populations with primary psychotic illness like schizophrenia and severe bipolar disorder also play a role, and you see more of that in some populations than others. As an African-American myself, I've always been struck by the idea that we may see different types of smoking in African-American populations than you may see in other populations, in what they may actually smoke and what particular brands they may use. I think that we all appreciate that we must understand that very, very well and use that data point to capture a better overall history from all our patients. We want to know as much about their process of care concerning what medications they receive, as well as what foods they ingest, their diet, as well as what other type of concerns such as environmental stimulus, such as smoking that they may actually employ. So the bullet point points out that different ethnic groups in the U.S. have varying attitudes towards seeking psychiatric care and starting psychopharmacological treatment. There's also, I think, a huge point in this discussion that many persons may have a lack of trust about how we refer them or what information we give is key. One doesn't have to only go all the way back to the 1972 admission that we had had a 40-year study. I read about it in a book called Bad Blood when I was in college in the mid-'80s, the Tuskegee syphilis study, which had lasted 40 years from 1932 to 1972. Finally, a spotlight was shown on it and all became aware that we as a government had not been truthful and earnest and honest in our actions towards this one population in Macon County, Alabama, Tuskegee, Alabama, and therefore had engaged in behavior that put a certain amount of African-American men at a greater risk of not only contracting, they already had it, but maintaining and not being treated for the purge of the issue, scourge of the issue of diagnosis of syphilis. That issue has stuck, I think, in the back of people's minds for not only years and decades, but even longer. I mean, I've heard about it throughout the course of my career and still hear about it today. So many people understand and appreciate that. And that issue of the lack of trust, I think, carries over to other groups, including physicians in this setting. And I think it's a barrier that we have to be mindful of, think about, and try to address. For me, very often, I think the trust also comes out in psychiatry. I'm aware of the data that shows that in all areas of medicine, the area of medicine where individuals are most likely to get a prescription and never get it filled the first time is psychiatry. And I repeat, if you really think about how difficult it is in all practical aspects of life to get a prescription, very often you have to get an appointment, whether you have insurance or not, and you have to wait your time, and you have to take off work, perhaps, if you will, or get there via transportation. Some don't even have easy access to transportation. You have to sometimes wait in line. All kinds of challenges come into play. And at some point, if you see a physician and make a recommendation, you think that all that you'd gone through, it would be most likely to be very important to them to get to the pharmacy, get that prescription filled. The reality is this idea and this data point that shows that in our profession, many patients never get the first prescription filled, to me, really points out to these altered attitudes that pre-exist, and that patients actually come to a psychiatrist with in mind in advance. And because of that, after we go through our entire process, hopefully make a qualified and a quality-oriented diagnosis and develop a treatment plan, and maybe that ends with a decision on medication management, including production of prescription, the patient still can't get past the hurdles of the obstacles that actually cause them great difficulty in trusting us and believing that those of us in psychiatry have the best interests at heart, and we actually don't provide more help for them than harm, then one can imagine why these attitudes towards seeking care are altered and change in the African-American community and other communities of ethnic variation with these social and cultural changes very often coming to play and limit our ability to provide optimized care. Next, we'll talk about diagnosis and treatment, as well as prognosis in this whole arena of health disparities. Wrote a book about health disparities about six to seven years ago, and I was struck by a couple of things. One, I wrote a book with a group of colleagues, and we talked in the book about the idea that maybe we begin to see a diminution or decline in health disparities as the Obamacare or the ACA, the Affordable Care Act, was coming to fruition. Affordable Care Act was passed in 2010, went through the Supreme Court and was okayed or validated June 12, 2012. My book came out in September of 2013, and I made these great pronouncements. I may not do that again if I write another book because I was surprised then as I am now, eight years later, in early 2021, how much challenge there's been at the national level and the government level to go against what many of us in medicine think are very clear concerns that we should have optimized open access to healthcare and that would limit healthcare disparities, especially mental health disparities. My book emphasized that Black Americans were more likely to seek mental health care from their primary care physician, rather from their psychiatrist, rather than from their psychotherapist. And I think that's a very important point to make when we're talking about the health disparities from a comparative to Caucasians. We've had data on this, I think, for some time. It says a lot of things to me that all I think address this issue of why there's ethnic issues in the practice of psychopharmacology and the practice, I think, of overall provision of better overall healthcare. One may be that for any of a number of reasons, a PCP, or a primary care physician, has a better opportunity, some would argue, than a psychiatrist. For one issue, the PCP often touches the patient. And for many patients in the Black community or other ethnic minority communities, they believe that if you're a real doctor, you'll touch them or examine them. Probably a challenge to us to appreciate, maybe we should actually conduct a real physical. We stopped doing that a half century ago, thinking that to provide analysis, you couldn't be a primary care doctor or touch or physicalize a particular patient. That may be a reason this type of data may argue we should reconsider that as we educate our young people, I think, going forward, now that we're in the 21st century. The next bullet point I want to emphasize is that as a result, that they're less likely to be prescribed a psychiatric medication. Well, think about it. If you're a psychiatrist, and the patient doesn't want to come in the first place, if they're very reluctant to share information with you in an overt and a frank fashion, if they clearly give a great deal of an obstacle or resistance to engaging with you as a doctor, you may think that, well, this is somebody who isn't psychologically minded, is a term we often have used in psychiatry, I think, inadvertently for black patients, or you might think that what really matters is they should get some type of sleep. And you might just tend to lean toward managing minimally and modifying your concerns to just address symptomatic issues and not really dig deeply and understand what the actual psychiatric diagnosis may be and provide an overall treatment plan that's optimized for that patient. And the third and final bullet on this slide is that African Americans and Hispanics have also been shown to have longer courses of mental illness or psychiatric illness, and overall, unfortunately, greater disability as a result of SPMI or chronic and severe persistent mental illness. Orders to follow a course could certainly be a lack of going to a doctor early on. If an autism medicine, like in psychiatry, if we start late, we're less likely to have a quicker response, and we're also less likely to get full remission. But very often in autism psychiatry, once you start treating a problem, you want it to be stabilized, hopefully in six months or less, definitely six to 12 months. And probably the first six months after that, you don't want there to be any kind of response as you're trying to get to a remission and probably takes another two years where if you don't have a relapse, you can get to full recovery. All issues that are challenged in psychiatry by patients who may question what we've done in the first place, may become medication non-compliant or only partially compliant because of that, or may follow the medication rules, but not trust or believe in the doctor and the treatment plan enough to follow other recommendations, such as don't use your medications and drink alcohol, or don't use your medications and engage in other actions with a lack of hydration or die to use other theories we consider that also help accentuate the likelihood of overall better clinical response. Okay, my next to last slide just points out that that whole issue really leads to the concept of stigma. Social stigma is related to mental health care is another factor plaguing, I think many ethnic minorities in America. I can see stigma simply as issue of fear. Persons are afraid of the psychiatrist, people like myself and my panelists here, they also be afraid of psychiatry. They're afraid because what they've heard externally in the media and on television and other settings has been adverse. And what they've also heard internally in their own homes and neighborhoods from their friends and relatives and the teachers in school, or persons who they believe and trust in may also be negativistic to what psychiatry is and what we aim to do. One challenge obviously has historically been the issue of civil commitment. The fact that we can civilly commit someone and take the rights of freedom away because we're doing it to decrease the likelihood of self-harm, of suicide most commonly, or either harm to others. But the reality is that actually has created an overt fear of us. And I think we have to be very mindful and try to educate our whole community and society as well as various individuals that civil process is to be done to their benefit or for the benefit of society to take persons who may be at risk of harm, not due to any adversity, but based on the fact that their brain isn't working right. Those are huge issues and a huge hurdle for us I think as psychiatry to carry and to cross. Latina and African American women are more likely to have stigma related to mental illness treatment. I think this bullet points out that Caucasian women are we see that in other settings. I mean, clearly there are more persons who are Caucasian across the board who go to the psychiatrist and more I think who are women who go to psychiatry. So you probably do see some differences based on ethnicity, based on gender and both collectively. So we point out that that may lead to persons being more reluctant to seek treatment in the first place or receive psychopharmacologic drugs. Think of the medications themselves are the problem. Early in my career, I had a radio show. It was funded by a local entity. Did it for a couple of years. It was an hour long show once a week. And I was always struck by how often regardless of what the topic was we were discussing that day somehow, some way, someone would bring up the issue as a caller in would call in with questions about the medications and the diagnosis of ADHD. People were just fascinated with the diagnosis of ADHD or then it was struggling whether it was ADD or ADHD, if you will. I think that very often they were struggling whether it existed or not. Challenged whether or not the same symptoms that they as adults may have had being hyperactive or over-engaged or if you will a short attention span when they were younger but at this point they had become adults who were functional in their own word or in their own perspective. They may have wondered if somehow caused difficulty and the difficulty that they really didn't need to have treated I think by their children or by their relatives. So huge issues regarding stigma across the board in our profession. That's one example of how it was actually very problematic. I'll end with this comment on the slide on access and parity. Disadvantages that increased across the board. Juki's access to care, parity ability to provide care. I think we've had parity issues in psychiatry for some time going back to I think it was 2009 of federal law by Domenchie out of New Mexico and Wellstone out of Minnesota that passed the Parity Act. And I think we've been struck throughout the course of the last decade in my career at how rarely it's followed even more how rarely governmental interventions actually enforce the Parity Law that's on the books now that requires insurance companies, government or private when they're providing healthcare, to show that there's parity. My entire career has not been parity. A, very often there are lower lifetime caps for psychiatry than other use of medicine. B, there are often higher co-pays and more limitations on which medications you can use and more limitations on how many days you can hospitalize. Across the full board, I think that for us that points out that patients lose access and our society loses equality in healthcare and psychiatry, i.e. parity, if we in psychiatry don't speak up and speak out and be heard and active I think in our activities. That's a huge issue I think for us as individuals, doctors, but also for our national organization, the American Psychiatric Association. The bullet point emphasizes that blacks are more likely than whites to receive paraprofessionals, social workers and nurses or psychologists than professionals in psychiatry. Or compared to whites, blacks with co-occurring mood and anxiety disorders and substance abuse are less likely to receive services for mood disorders. So the idea would be that many people come in with a co-occurring illness, I described that earlier, maybe they have alcohol dependence disorder and they have major depression. And if you're African-American, the data by Cummings pointed out that you're a lot more likely to be treated as a solo diagnosis, just a person with alcohol or cocaine dependence. And I think the reality is because our society all too often likes to overly criminalize those concerns versus medicalizing them and seeing them as individuals who need medical help by treating medical prevention. I've also thought in my career that in order to get better overall determinants of care, when you're talking about psychiatry, psychiatrists should be the ones doing the talking. A slide points out that there are cultural perspectives, side effects as well. Whether individuals view the side effect to be bad, deleterious, or just indicative of the medicine is working, is really tied to context. I've often thought that, we try to use examples in psychiatry in our community about cancer. My father, as a personal example, had cancer and we realized when he got the cancer treatment and his hair fell out, that the medicine was working. So we believe that was a good thing that the hair fell out that perhaps meant that the medicine was working to address the cancer. A huge difference for us in psychiatry where there's a remarkable fight has been throughout my entire career where patients often at the first sign of any side effect want to stop the medication or throw it away or not come back to the doctor at all. I've often told students and trainees and my patients that the most important visit for me when I get a new patient is the second visit. Because all too often the reality is, if people don't come, if patients don't come back to you the second time after an initial visit, they probably have not developed the kind of confidence and trust in me as a doctor that's likely to work for them over the time I'm gonna need to work with them to really get them better, let alone get them the full remission. There's one study I think by Lynn showed that the change in evaluating cultural variations and how we interpret side effects for licking, for example, research has found that Caucasian or white patients viewed and reported the medication-induced polydipsia and polyuria, increased thirst and increased urination as adverse effects. Those same effects were viewed in Chinese patients as evidence of pharmaceutical efficacy, that the medications were actually working. So clearly there are differences in culture that matter, differences along the line of efficacy, as well as along our side effects, and also because I think in how we communicate with patients and how they actually come into the equation of working with a doctor in psychiatry, it's likely to work more effectively for them. So in summary, I end by simply making an argument, I thank very much for the opportunity to kind of join the group, a really excellent panel, excellent discussion, a lot to think about for doctors of all types when taking care of patients or who may have ethnic psychopharmacological differences in care. Thank you very much. I wanna thank everyone for being a part of this, the ethno-psychopharmacology and those who are listening. We did have a few questions from the audience about two of our presenters today. And so the first question is for you, Dr. Lawson, how do you recommend communities, what do you recommend communities do that are in food deserts, where the foods that they're eating may actually be decreasing the efficacy of medications, be it psychotropics or even for other medical specialties? Well, I think that when we talk about diet, because of a lot of pop diets and so forth, is there's more of an emphasis on what we're taking in the U.S. than probably there should be. The bottom line is get a balanced diet wherever you can. Now, saying that, when you start having, in the U.S. the problem is not that we don't get enough food, but that we have too much food that is high carbohydrate, high fat, and so forth. And as a result, that is a much major factor than to have vitamin deficiencies. Vitamin deficiencies, inappropriate nutrients can be effective in terms of medication effects and in terms of pharmacotherapy, but it's not a major issue in terms of the United States. We did a study showing that it can be effective. For instance, it's well known, it's now known that if you move tyrosine hydroxylates as some of the precursors for some of the neurotransmitters, you can actually induce depression. But that is very unlikely to happen in the United States because we have more than enough food to be able to overcome that. But again, saying that, the problem is that it's not so much as deficiencies as a result of lack of access, but deficiencies in terms of other factors, such as distortions from ketogenic diets, alcohol, and so forth, in which we deliberately limit certain essential nutrients that may be necessary for health. All right, thank you, Dr. Lawson. Dr. Cho, have you actually seen where there's an issue between the doctor and the patient so far as not understanding culture or communication problems that where, when that occurs, it actually impacts overall outcomes in patients? Yeah, actually, even before medical school for myself and working in public health, there in Inland Empire of Southern California, there's a lot of issues in terms of health disparities. Oftentimes, the consideration of health disparities is not just a Latinx and white or black versus white, but it's just all, it's an issue for all ethnic groups. So there's the health disparities that all of those populations, all of those populations experience, but with some cultures, for immigrant cultures from Asia, also have a language barrier, just like Latinx communities would also have a language barrier, but the resources aren't as available. So oftentimes what you'll see is not really taking, the provider not really taking the time to delineate what the concerns and truly getting informed consent and not really taking a thorough history in terms of what other medications, diet, other social factors may play. So I have firsthand seen, even before I started medical school, some of the deleterious effects of these disparities. If we were talking specifically about, again, polymorphisms, although we've not been able to prove it, there have been incidents where we, I've seen, again, carbamazepine as a culprit for rashes, the SJS, TEN kind of rash. So these things do happen, although it may not be as known. And Dr. Cho, do you have any suggestions on what a clinician could do in order to help decrease these issues of culture and how these disparities are impacting patient outcomes? That's a great question. I think the biggest question is just increased resources in terms of translation services. Without the appropriate communication, we always talk about history in the medical field, we always talk about history and getting a thorough history and how important that is. And if there's a language barrier, that's definitely not gonna happen. So number one is increasing resources to translating services, making sure they're all available and used as much as they should be. The other thing, of course, is more education programs to enlighten, again, programs like this that show that we are not equal. We're not all created the same. We have variations. We're all unique, complicated individuals that have different nuances. So I think the more programs like this and the more we can raise this banner and get the word out that medicine needs to be individualized. There is no blanket one size fits all formula for everybody. And the more we can hone in on the individual needs of our patients, the better care we're gonna provide. And as Dr. Bailey suggested, the more therapeutic alliance will be created and better outcomes for all. All right, thank you, thank you. And Dr. Bailey, following up on that, what do you believe we could do regarding the lack of trust between the community and the actual clinician when it comes to issues of race? Well, again, I think as you said earlier, these questions are remarkably timely and probably all four of us have spent our entire career trying to find some answers to them. So my suspicion goes up as high as well because we hope we can find some better answers. I'd say three things briefly. AI, I think programs like these that promote positive, effective and accurate information, I would imagine could only be helpful. So we need kind of a wide distribution of such, if you will. More should hear it rather than less. I think secondly, persons like ourselves should avail ourselves, I think, to local community activities. I was in Houston, Texas once and I had the radio station on on a Sunday morning and a guy was given remarkably important and effective information about child psychiatry. His name was Napoleon Higgins. And although I may have known him, others who didn't know him, I could hear a level of integrity and grasp of the information that made it culturally relevant and real and in a way that would make it more likely believable. So somebody that Higgins may never see, you, Ian Higgins, may actually go to the doctor now and acknowledge that the child's having trouble because they heard somebody on television, on radio, say it in a way that kind of made sense. So I think we have to reach a wide audience and we have to do it in a fashion that is culturally relevant and seems correct to them because they won't be afraid. The third big point I'll often say is I think when people talk about psychiatry, psychiatry should be the one doing the talking. They say very often that there's a discussion about, without a vaccine, you got a ID doctor, Fauci, on television and they're discussing cancer. There's a cancer doctor, MD Anderson, on television, if you're in Houston or I'm out here in LA. But very often it's somebody discussing psychiatry as a non-doctor and a non-professional trained person, not a psychologist or a social worker. It's a celebrity expounding on psychiatry. So the media hurts us, in my opinion, in those settings, much more so than they realize, by giving the impression what we're doing is not medical or based on empirical data. I think those are three things that could help to reach, to strengthen the trust concern. All right. And Dr. Lawson, I'll leave the last question for you, question for you as chair. What do you think that we could do in order to get more ethnic minority diverse researchers to do this type of work where we're being able to see more of a diverse population, therefore improving all clinical care for our ever-growing diverse population in America? Well, I think you and Dr. Bailey both talked about it in terms of the actions done by the National Medical Association and others to reach out and involve clinicians who are actually in the field to become involved in research, to help in all phases of getting information that can lead to clinical trials, making sure they're involved in terms of the determination of what studies we should do, being involved in terms of patient recruitment, and also being involved in terms of actually carrying out those trials, not just in very, very limited academic centers, but also in the community so that we can see that results are meaningful. One of the things that I've been impressed with is that when we have community involvement in all phases, one, we help recruit more clinicians who wouldn't be involved in this work before because they're actually seeing it providing a positive result to their patients. And then two, we're actually seeing that the community is recognizing that research and activities are not being done by people who are culturally and socially distant from them, but by people who look like them, who think about their concerns, and who recognize the importance of their concerns. And then three, people are now becoming involved in activities that will lead to meaningful results that they can see. We're seeing this right now in terms of the coronavirus epidemic. And what we're seeing, and also that we saw it again in the AIDS epidemic, what we saw was that initially, often African-Americans were not involved in these trials, did not participate. But those groups, those who reached out to indigenous cultural activities, such as the churches, the barber shops, as well as the beauty parlors, we got more involvement of the community. We got more involvement of our professionals who said this is something that not only is helping science, but also helping our communities, and also helping me because it's giving some meaning to what I am doing. I think when we do that, we get much more active recruitment of folks, much more active involvement in folks, and much more meaningful results in terms of what we're contributing to the community. So in some ways, I think the coronavirus epidemic has done also some awful things, but it's also showing that again, if we wanna come up with helpful and meaningful results, we need to get all courts pressed in terms of all components of the community to try to address the healthcare concerns in our communities. Thank you, thank you. Any closing words, Dr. Lawson? Yeah, I think that this, I'm glad to see that we're having the Ethnocyclopharmacology program again. I wanna thank Dr. Bailey for pushing ahead with this. For a while, we tried to have these at every APA meeting, and we didn't, we didn't. And I didn't know it was a result of a loss of interest by psychiatrists in terms of what's happening, and what's happening with drugs. I didn't know it was a lack of interest of appreciating the importance that culture plays in terms of our medication. But whatever the case, I think this is a good indication that once again, we're gonna be involved with an issue that is extremely important in terms of complete and full engagement in the community in terms of the treatments that we offer. Thank you all so much. Thank you, you are excellent panelists. ♪♪

ethno-psychopharmacology

individual variations

drug metabolism

ethnic differences

access to care

stigma

genetic differences

cultural influences

clinical trials

diverse populations