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A Surgeon General's Perspective on Cultural Competency: What Is It and How Does It Affect Diagnosis and Treatment of Major Depressive Disorder?

  • Authors: David Satcher, MD, PhD; Philip T. Ninan, MD; Prakash S. Masand, MD
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Target Audience and Goal Statement

Physicians, physician assistants, nurse practitioners, nurses, psychologists, social workers, certified case managers, pharmacists, and other healthcare professionals with an interest in mental health.

The mental healthcare delivery system is especially sensitive to the effects of culture in a variety of ways. Culture, ethnicity, and race-related constructs dictate the ways in which information is transmitted and received by both patients and clinicians. Cultural insensitivities can lead to misdiagnosis, diminished therapeutic alliance, and ultimately poor outcomes. Cultural competency, on the other hand, is the degree to which the clinician is attuned to the traditions, perceptions, and histories of diverse patient populations. In major depressive disorder (MDD), stigma may lead patients from different cultures to first present with somatic complaints rather than psychological symptoms typically associated with the disorder. Additionally, clinicians should be aware of potential racial and ethnic differences in pharmacokinetics of drugs that may impact their metabolism, effectiveness, and side-effect profiles. In this evidence-based psychCME TV activity, the experts will address the elements that can minimize the effect of the ethnic differences and lead to culturally competent patient care in major depressive disorder.

Upon completion of this activity, participants should be able to:

  1. Define cultural competency.
  2. Identify factors related to culture and ethnicity that influence recognition and diagnosis of major depressive disorder.
  3. Assess the influence of race and ethnicity on pharmacokinetics of medications used to treat major depressive disorder.


  • David Satcher, MD, PhD

    Director, National Center for Primary Care, Morehouse School of Medicine, Atlanta, Georgia


    Disclosure: Grant Support: Wyeth Pharmaceuticals; Board Member: Johnson & Johnson; Speakers Bureau: American Program Bureau.

  • Prakash S. Masand, MD

    psychCME Chair; Consulting Professor of Psychiatry, Duke University Medical Center, Durham, North Carolina


    Disclosure: Grant/Research Support: AstraZeneca, Bristol-Myers Squibb, Forest Laboratories, GlaxoSmithKline, Ortho-McNeil, Janssen Pharmaceutica, Wyeth; Consultant: Bristol-Myers Squibb, Forest Laboratories, GlaxoSmithKline, Health Care Technology, Janssen Pharmaceutica, Organon, Pfizer Inc., Wyeth; Speakers Bureau: Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Novartis, Pfizer Inc., Wyeth; Stocks: psychCME, Inc.

  • Philip T. Ninan, MD

    Professor of Psychiatry and Behavioral Sciences; Director, Mood and Anxiety Disorders Program, Emory University Medical School, Atlanta, Georgia


    Disclosure: Grants/Research Support: Cephalon, Cyberonics, Eli Lilly, Forest, GlaxoSmithKline, Janssen, NIMH, Pfizer, UCB Pharma, Wyeth; Consultant: Cephalon, Forest, Janssen, UCB Pharma, Wyeth; Speakers Bureau: Cephalon, Forest, GlaxoSmithKline, Janssen, Pfizer, Wyeth.

Accreditation Statements

    For Physicians

  • This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME). CME Outfitters, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

    CME Outfitters, LLC designates this educational activity for a maximum of 1.0 Category 1 credit toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

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There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

Follow these steps to earn CME/CE credit*:

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A Surgeon General's Perspective on Cultural Competency: What Is It and How Does It Affect Diagnosis and Treatment of Major Depressive Disorder?

Authors: David Satcher, MD, PhD; Philip T. Ninan, MD; Prakash S. Masand, MDFaculty and Disclosures


A Surgeon General's Perspective on Cultural Competency: What Is It and How Does It Affect Diagnosis and Treatment of Major Depressive Disorder? Presented by Chair and Moderator: Prakash S. Masand, MD; Faculty: David Satcher, MD, PhD; Philip T. Ninan, MD

Program Introduction and Objectives

  • Dr. Masand: Welcome to psychCME TV. America is a multicultural society and the patients who we see in our practices reflect that. Unfortunately, culture and ethnicity have been neglected in traditional psychiatric research. As a result, clinicians like you and I often struggle with cultural issues, often compromising patient care. And that is the focus of today's psychCME TV program.

    Today's program is titled, "A Surgeon General's Perspective on Cultural Competency: What Is It and How Does It Affect Diagnosis and Treatment of Major Depressive Disorder?"

    Let me now welcome our guests. Joining me today in the studio is Dr. David Satcher, Interim President of the Morehouse School of Medicine and Director, Center of Excellence on Health Disparities, in Atlanta, Georgia.

    Dr. Satcher: Thank you, Prakash.

    Dr. Masand: Also joining me is Dr. Philip Ninan, Professor of Psychiatry and Behavioral Sciences at the Emory University School of Medicine, also in Atlanta, Georgia.

    Dr. Ninan: Thank you.

  • Slide 1.

    Slide 1.

    (Enlarge Slide)
  • Dr. Masand: Today's program has 3 learning objectives: first, to define cultural competency.

  • Slide 2. Learning Objectives

    Slide 2.

    Learning Objectives

    (Enlarge Slide)
  • Dr. Masand: Second, to identify the factors that are related to culture and ethnicity that influence the recognition and diagnosis of major depressive disorder.

  • Slide 3. Learning Objectives

    Slide 3.

    Learning Objectives

    (Enlarge Slide)
  • Dr. Masand: Finally, to assess the influence of race and ethnicity on pharmacokinetics of medications used to treat major depressive disorder.

  • Slide 4. Learning Objectives

    Slide 4.

    Learning Objectives

    (Enlarge Slide)

Defining Cultural Competence

  • Dr. Masand: David, if I could begin with you. You were the first Surgeon General to put out a report on mental health, which really made such a remarkable difference to our field. Let me ask you about the terms "culture, race, ethnicity." They're often used by all of us, sometimes confusing to our audience. So, if you could take us through some of these terms.

  • Slide 5. Learning Objective 1

    Slide 5.

    Learning Objective 1

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  • Dr. Satcher: Let's start with culture. And generally when we speak of culture, we're referring to shared values, shared beliefs, shared norms, even shared perceptions, and connections that people have with one another.

    And so, culture is something that is very important in the lives of people in their day-to-day behavior. Ethnicity can include culture, but basically ethnicity is having a common heritage, and in some cases not having the same culture but having a common heritage; sometimes sharing things that you enjoy, whether it's food or music. So, ethnicity refers to that. We have begun to use ethnicity in keeping health data nationally, much more than we did before.

    Race is an interesting term because historically, we thought of it as based on genetics. And in recent years, especially with the Human Genome Project, it's become very clear that genetic variation is even greater within races than between races. So, there is no "genetic basis" for race.

    Now, having said that, it does not mean that a racial group like African Americans may not share genes for sickle-cell disease more than other populations, or Ashkenazi Jews, Tay-Sachs disease more than others. But genetics is not the basis of race.

    Dr. Masand: David, another area that you've done a lot of work in is the area of cultural competency. Tell our audience, what is it and why is it so important to our patients?

    Dr. Satcher: Well, as you said earlier, we live in an increasingly diverse society. And it's really critical, if you're going to take care of patients, that you have the skills and the capacity to deal with a lot of different cultures. And so, having that capacity and being able to transform programs into that capacity is cultural competence. It's great when an individual can understand different cultures. But within the healthcare team, you need a diversity to deal with the variety of cultures. That's cultural competence.

    Dr. Masand: David, one of the questions that clinicians will often ask is, "What can I do as a clinician to become competent in dealing with cultural issues in my practice?"

    And I know you've come up with a very nice mnemonic, which spells out a CRASH course on cultural competency. Tell us a little bit about CRASH.

  • Slide 6. Cultural Competence

    Slide 6.

    Cultural Competence

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  • Dr. Satcher: Well, at the Morehouse School of Medicine, we have this course called a CRASH course in cultural competence and a lot of people think that means that "crash," right away, you can understand it. We don't believe that.

    CRASH is an acronym. The C stands for consider culture when you're interacting with patients, consider culture in this role. The R stands for respect; very important to respect other peoples' cultures. And that has to do with how you call people; do they prefer to be called by their first name or last name? But respect their culture.

    The A has a double meaning: assess culture but also affirm it; make sure that you give some positive feedback about the person's culture. The S also has a double meaning: first, being sensitive to the other person's culture as you try to evaluate their health problem, but also it means being aware of your own culture; self-awareness is really critical.

    And finally, the H is important; it stands for humility. And it's based on the fact that none of us will ever become experts in other peoples' culture, but if we have the right humility, we relate to them in such a way that they really help us to understand how their culture's impacting upon on their problem.

    Dr. Masand: David, let's go back and visit the issue of why culture is important in the patient-provider interaction. And let's look at it from 2 different perspectives. Let's first look at it from the patient's perspective and then, maybe, from the provider's perspective. So, take us through some of the reasons why it's so important.

  • Slide 7. CRASH - Course Concepts

    Slide 7.

    CRASH - Course Concepts

    (Enlarge Slide)
  • Dr. Satcher: Culture's very important. And I think much more important than we have observed in the past. For the individual patient, culture determines how that person experiences and manifests an illness. And that's really critical. It also helps to determine how they cope with the illness; how do you deal with an illness when you have one? How do you deal with the stresses that go with an illness? And then, finally, when, how, and where a person seeks treatment is greatly related to that individual's culture. And so, as you can see, it can have a major impact.

  • Slide 8.Culture Counts in the Quality of the Patient-Provider Interaction

    Slide 8.

    Culture Counts in the Quality of the Patient-Provider Interaction

    (Enlarge Slide)
  • Dr. Satcher: However, at the same time, the provider brings his or her own culture to the table when interacting with patients. It might determine what questions you ask or your index of suspicion, how you diagnose the problem. Even how you treat the problem can be affected by culture; that's been demonstrated in studies. And finally, then, there's sort of the culture of the healthcare system that sort of determines how we fund things, what we fund, etc.

    Dr. Masand: Phil, do you have some thoughts on some of the issues that David raises in terms of diagnostic issues, in terms of treatment issues, both from a patient's perspective and provider's perspective?

    Dr. Ninan: I think David has articulated some of these boundaries and the overlap between issues like culture and ethnicity. And I would also say that the advances in neuroscience, in terms of understanding what's going on in the brain, really mirrors what we have learned from the report that David put out when he was Surgeon General.

    For example, in the past decade, they've discovered the system in the brain that allows us to be able to represent the observation of an action or the emotion that is expressed by somebody else, internally, in our own brains. And so when we observe an action or an emotion, we actually simulate that in our own brain. And that's the basis of social interaction.

    So when, as David was saying, you're seeing somebody from a different culture, if that person is expressing an emotion that you cannot identify with, then the bond that you will experience with them is going to be different than if you identify with that patient and you have some empathy that you are experiencing. And that has an incredible contextual influence on how you will filter subsequent information. And this is the brain basis, so to speak, of the cultural competency that David is talking about.

  • Slide 9. Culture Counts in the Quality of the Provider-Patient Interaction

    Slide 9.

    Culture Counts in the Quality of the Provider-Patient Interaction

    (Enlarge Slide)

Factors Related to Culture and Ethnicity

  • Dr. Masand: Phil, I think that's a very nice lead-in to our second learning objective which I'd like to touch upon, which is to begin to identify the factors related to culture and ethnicity that may relate to the recognition and diagnosis of psychiatric illness. And we're going to focus on major depressive disorder. So, take us through some of the differences in symptom expression, in illness expression, in treatment-seeking behavior that culture plays a role in as it relates to major depressive disorder.

  • Slide 10. Learning Objective 2

    Slide 10.

    Learning Objective 2

    (Enlarge Slide)
  • Dr. Ninan: To start out with, we are looking at broad, general statements. But as Dave pointed out, just like the genetic differences are much greater within an ethnic group compared to between groups, there are also tremendous differences from one individual to another.

    But we can make some broad statements about different ethnic groups. Some cultures, for example, express distress more as physical symptoms. So we would call that "somatization," rather than emotional distress. Now, why that might be important would be that if somebody's expressing emotional distress, then one might be able to be empathic, because you mirror that emotion internally when you are with that particular patient. You are less likely to be able to do that if they are expressing it more somatically. And so, that might be an issue that I think is very relevant in terms of depression.

    Patients might go, particularly to primary care doctors, and be presenting not with sadness and anhedonia, but might be expressing themselves more with irritable bowel or cardiovascular symptoms and, therefore, it's critical to think about depression or anxiety in one's differential diagnosis. You see this in terms of different cultures.

    But it's also important to point out some similarities. For example, when you look at mental disorders in African American populations, it is actually no different compared to Caucasian Americans if you control for education, income, and marital status.

    On the other hand, there's a 3.5-fold increase in homelessness in the African American population. And homelessness is going to be an important mediator of mental disorders.

    And so, you have to be able to look at these kinds of issues so that your natural biases (when you see somebody in the emergency room, for example) are not going to be influenced by the homelessness issue vs the ethnic background that a patient might have.

    Dr. Satcher: I think that's very important. And homelessness is a good example because some studies now show that over half of the homeless people in this country are suffering from a mental illness. So they sort of work back and forth with each other. This is so important because some studies suggest that one third to one half of patients who suffer from depression are not on treatment.

    And, as you say, a lot of them are being seen in primary care practices, and considering the fact that if a person is depressed, it would be very hard to control their diabetes or treat their cancer or hypertension.

    It's really critical that we do a better job at diagnosing depression as early as possible. This is a very important point.

    Dr. Masand: Phil, one of the other things we often will notice in our practice is that there are certain terms that are not used commonly in certain cultures to express illness. Depression is a term, for example, that is not as commonly used by Asian Americans compared to Caucasians. And how does that influence the diagnosis of the illness, based upon the criteria that we use, and then, as certain cultures express their illness using those criteria?

    Dr. Ninan: That's correct. For example, in several American Indian languages, the words "depression" and "anxiety" don't have appropriate translation words. So they don't have the vocabulary to be able to express that. And so, it's important to be able to ask individuals to describe their experience and to be able to read what the meaning is behind some of the words that they're using.

    We actually have very little information on the prevalence of mental disorders in different ethnic groups in the United States. The National Comorbidity Survey, for example, which is our best epidemiological study that has been done, had only about 2% to 3% Asian Americans. And as you know, there are about 43 different ethnic groups that are categorized by the federal government as Asian Americans. There are fundamental differences between these groups, even though they've been lumped together within our federal system.

    Within the Hispanic Americans, for example, there's an interesting study that was reported in the Surgeon General's Report that showed that mental illness among Hispanic Americans was lower in those who had been born in Mexico and then immigrated to the US compared to those who had been born in the United States. You wouldn't expect that 1-generation difference would have that much of an impact from a genetic standpoint. So clearly, environmental factors are important in terms of the context that they have in the brain in terms of the experiences that they are having and how they look at that, the level of resilience that they're going to have, based on some of these early experiences.

    Dr. Masand: And Phil, it's not just a diagnostic issue. It's also a treatment issue because patients from different cultural groups, ethnic groups, may be treated differently either in the choice of treatments or in the dosing of medications. That may actually be a deterrent to appropriate treatment.

    Dr. Ninan: That's correct. So that, there are a number of issues that come in that might mediate whether somebody gets treatment or not.

  • Slide 11. Differences in Culture/Ethnicity

    Slide 11.

    Differences in Culture/Ethnicity

    (Enlarge Slide)
  • Dr. Ninan: Stigma is an important issue. So how somebody explains the illness, internally, in terms of the way they think about it, can be an important modifier in terms of whether those symptoms are propagated or whether they're dealt with in a more healthy manner.

    In many cultures there are beliefs, for example, in spiritual systems. In some of the far-eastern cultures, they believe that you might pay the price in this life for evil acts that you performed in previous lives. And so the sense of acceptance of pain and emotional distress is going to be very different if you have that belief system than if you have more of the traditional, Western perspective that the manifest of life that we have is what we're dealing with.

    So, spiritual concepts like that are going to be critical in terms of trying to understand, particularly psychotherapeutic interactions, the context in which the patient is coming in for treatment.

    Another interesting bit of information is that 25% of African Americans report feeling that they've been discriminated against, often on a day-to-day basis, compared to 3% of the Caucasian American population. So if you have that belief system, how would you expect that individual to go in for help if you believed that the person who you're going to go to help for is going to discriminate against you?

    So, there are those kind of disparities in terms of access to care. These are cultural and ethnic kind of issues, not just financial and geographic and specialty care issues that impact how ethnic and cultural issues â€' ethnopsychiatry â€' impact care in mental illness.

    Dr. Masand: David, you've seen that in your practice yourself.

    Dr. Satcher: Yes, this is so important because one of the major problems that we have in our healthcare system is the time at which people present with problems. And if you're African American and you don't trust the healthcare system, it means, among other things, that you're not going to go until the pain is unbearable or the problem is life-threatening.

    And we see that every day in practices in the inner city and the rural communities. We see people coming in with the problems they've had for a year or 2 years or sometimes more. So, this whole issue of whether you trust a system within your culture, whether the healthcare system is friendly or unfriendly, can be very critical in terms of our healthcare system.

    And the issue of stigma that you mentioned is also so important because it affects all groups in this country. The stigma surrounding mental illness means that individuals delay treatment for mental disorders, parents delay seeking treatment for their children until it's very late in the illness, and we have a healthcare system that suffers from stigma. We have trouble getting policies that are mental health-friendly.

    Dr. Masand: David, this brings up the question for clinicians of what kinds of questions should we -- as physicians, as clinicians, as nurses, as pharmacists, as psychologists -- be asking our patients to kind of assess their health beliefs? Because unless you assess those, as Phil mentioned and you've mentioned, it may be difficult to make an intervention.

  • Slide 12. Stigma Deters Treatment

    Slide 12.

    Stigma Deters Treatment

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  • Dr. Satcher: I think the first is to have the right attitude, and that is that you really want to see this problem from the patient's perspective and not just from a medical perspective.

    Kleinman has come up with a list of questions that we use a lot. But they are questions that basically try to get at the world view of the patient. How do you see this illness? What do you think caused it? How does it make you feel? What do you fear most about the illness that you're having right now? How has it changed your life? What do you expect to happen in the future with this illness? Those kinds of questions get at the perspective of the patients and the culture of the patients. Some patients see their illness from a spiritual perspective. And if you don't appreciate that, it makes it very difficult to be effective in diagnosis and treatment.

  • Slide 13. Kleinman's Questions to Assess Health Beliefs

    Slide 13.

    Kleinman's Questions to Assess Health Beliefs

    (Enlarge Slide)
  • Dr. Masand: David, let's say we've asked those questions that you've enunciated so well. How does it affect the presentation of an illness, like major depression, in one's practice based upon some of the answers to those questions?

    Dr. Satcher: It's a good question and there are several examples. Since we're talking about major depression, I think one of the examples that I reflect on (of course, there are many stories) is the story about an African American man. He was a truck driver, drove all over the country, and became very depressed. And when he was seen, he expressed it by saying, "The devil is riding in the truck with me." From a spiritual perspective, he saw his depression as an evil spirit; the devil was with him. And unless you appreciate where patients are coming from in terms of their own vernacular, you can miss a diagnosis. He didn't come in and say, "Oh, I'm just feeling low and down. I have trouble sleeping or eating." No, he just said, "The devil is riding in the truck with me." And getting at that and appreciating that is what's critical in primary care, but I also think in general medical practice.

    Dr. Ninan: And not jumping to the conclusion that he has a psychotic illness.

    Dr. Satcher: Which often happens, by the way. African Americans are much more likely, in most studies, to be diagnosed as schizophrenic when they're not. And to not be diagnosed as depressed when they are. So, it's a very good point.

    Dr. Masand: Absolutely.

  • Slide 14. How Cultural Beliefs Impact the Presentation of Depression

    Slide 14.

    How Cultural Beliefs Impact the Presentation of Depression

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Effects of Race and Ethnicity on Pharmacokinetics

  • Dr. Masand: Well, Phil, let's turn to our third learning objective, which is to look at the effects of race and ethnicity on the pharmacokinetics of the medications that we use to treat patients with depressive disorders. So, could you take our audience through some of the factors, whether it's biological or cultural, that affect drug response?

    Dr. Ninan: This is the area that is called pharmacogenomics. And it's really the result of this incredible revolution that we've had with the Human Genome Project, that we've been able to identify the human genome, and that what pharmacogenomics does is it explores the inherited basis of the medication response differences among individuals.

  • Slide 15. Learning Objective 3

    Slide 15.

    Learning Objective 3

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  • Dr. Ninan: So, we're really looking at genes and much of the information that is available has focused on those genes that are involved in the absorption and the metabolism of medications. This is a family of enzymes, called the P450 enzyme systems. And they're largely present in the liver but they're also present in the gut.

    To give you an example on this, you take a pill, it goes through the stomach, and it gets absorbed through the small intestine. We can use an example of a calcium channel blocker, which has been best studied -- 100% of it is absorbed through the gut; that absorption is being mediated by the 3A family of these enzymes. If you have a glass of grapefruit juice that inhibits that enzyme in the gut, what happens is you have a substantially different proportion of the medication being absorbed because you had a glass of grapefruit juice. And that lasts for 24 to 48 hours. It also has an impact in terms of what's going on in the liver. So you inhibit the 3A family of enzymes, and there are medicines that do that.

    There are medicines that actually induce the enzyme so that it becomes more active. St. John's wort, for example, which is an herbal product that you buy over-the-counter in health food stores, has an effect in terms of inducing the enzyme. That means that that enzyme now is going to break down medications at a much faster level.

  • Slide 16. First-Pass Metabolism After Oral Administration of a Drug

    Slide 16.

    First-Pass Metabolism After Oral Administration of a Drug

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  • Dr. Ninan: So, this is where the absorption and the metabolism of the medications that might be mediated by the 3A family of enzymes, which is involved in 50% of the metabolism of medications, might have an impact on the effect of that medication.

  • Slide 17. Relative Contribution of CYP Isoforms to Drug Biotransformation

    Slide 17.

    Relative Contribution of CYP Isoforms to Drug Biotransformation

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  • Dr. Ninan: Now, there are differences that you would see between ethnic groups in the manifestation of these enzymes. So, for example, if you can have 1 amino acid, 1 base change in the production of an amino acid so you have a single nucleotide polymorphism, you can have a dramatic effect in terms of how effective that enzyme might be.

    And there are differences, for example, in the 3A5 isoenzyme where two thirds of the Caucasian Americans are deficient in that particular enzyme compared to only 50% of African Americans.

    And so, there will be these kinds of differences in terms of how they might metabolize these medicines. Now, we don't completely understand all of the factors that would influence this. So, we have to be cautious about the specific knowledge that we have in one area because there are alternative systems, like the alpha glycoprotein system, for example, that might also kick in if your primary P450 system is not working well.

    And so, while we are recognizing these unique characteristics, we really want to be looking at the patient in front of us, truly as an individual, and not have our biases in terms of ethnic backgrounds influencing our thinking. We should be able to say, "I'm going to prescribe this medicine to you. We'll see what your body and brain does with the medicine and we'll make the adjustments based on that." Rather than, "This is the dose that I'm going to get you to and you won't have any side effects and you'll be much better at the end of X number of weeks."

    Dr. Satcher: Again, this is so important.

    Obviously, this is very important field, pharmacogenomics. And we're going to learn much more in the future. But from a primary care physician perspective, it's interesting, the history is still the most important thing. I mean, unless you understand the patient's environment and the patient's lifestyle, including nutrition, you can miss a lot, is what I heard you say.

    And even when you start a patient on a medication, you can't know, just because of that patient's race, definitely how they're going to respond. So, the ongoing history as to, "How are you doing, Mrs. Jones? Are you feeling any side effects? If you know what the side effects should be with that medication, are you having them?" Because we find that a lot of times when we ask patients those questions, we find that they don't all respond to the same medications the same way, even if they're within the same racial groups.

  • Slide 18. Simulated Activities of Cytochromes P450 CYP3A4 and CYP3A5 in African Americans and

    Slide 18.

    Simulated Activities of Cytochromes P450 CYP3A4 and CYP3A5 in African Americans and Caucasians

    (Enlarge Slide)
  • Dr. Masand: Phil, as you pointed out and showed the audience, the 3A family is very important for drug-drug interactions, and may be responsible for more than 50% of drug-drug interactions in medicine, not just in psychiatry. The 2D6 isoenzyme has also received a lot of attention because some of the selective serotonin reuptake inhibitors (SSRIs) can inhibit the 2D6 isoenzyme. Are there differences amongst ethnic groups in terms of the allele frequency of the 2D6 isoenzyme?

    Dr. Ninan: Yes, there are. There are, at this point, about 13 genes that have been identified that have an impact on the functional expression on the 2D6. And that functional expression, based on these genes, varied by ethnic characteristics. So you find that about 75% of the Caucasian American population will have the expression of the 2D6 through the polymorphisms on these genes, compared to about 40% in African American populations.

    And so, with the tricyclic antidepressants, for example, which are metabolized through the 2D6, you can have a varying degree of differences in terms of blood levels. And as you point out, SSRIs, some of them are very powerful in terms of inhibiting the 2D6 isoenzyme. Now, the clinician of the not-too-distant future will actually have this information.

    In December of 2004, the US Food and Drug Administration (FDA) approved the first microarray chip to be able to identify the polymorphisms of these P450 enzyme systems. So we should be able to, in the not-too-distant future, have the information available to say that if I'm going to be prescribing paroxetine to you, this is what's going to be happening because you have this level of functionality of the 2D6 and, therefore, I should not be combining this medication with, say, a tricyclic antidepressant. And that level of information will allow us to be able to reduce some of the burden of side effects and, also, potentially be able to predict efficacy a little bit better.

    Dr. Masand: David, another area where this makes a big difference is in optimal dosing. And we know dosing is the key to treating patients with major depression. Can you give us some examples of how dosing may be inappropriate in different cultural or ethnic groups because the clinician is not appreciative of the fact that there are these pharmacokinetic differences that Phil alluded to?

    Dr. Satcher: I think it's a critical point. And there are several areas of example. Let me just pick one, and this is really from a study done in Washington, DC, at Howard University, among Hispanic patients, looking at their response to risperidone compared to others. And they found that these patients required a much lower dose to be effective and they tended to have more side effects as the dosage increased. That's one example but again, that was a study involving a few patients and the kind of thing you have to repeat.

    But the fact of the matter is, you have to be aware that people are not all the same when it comes to how they react to a given drug. And we see that everyday. We see it in the treatment of hypertension, how certain groups respond to one drug as opposed to the others.

    Dr. Masand: Phil, is it also possible that these differences may contribute to differences in discontinuation rates amongst the antidepressants that we use, or in response or remission rates being different in different ethnic groups? Are there any data to support that?

  • Slide 19. CYP2D6 Allele Frequency

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    CYP2D6 Allele Frequency

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  • Dr. Ninan: It's a very good question.

    A study was done by Alan Schatzberg in about 250 patients with major depression, and looking at the elderly population who were randomized to receive paroxetine or mirtazapine. And they looked at the polymorphism for the serotonin transporter promoter region, which has got a lot of attention lately.

    And what they found was that if the patients had the homozygous short alleles, that is based on their genes, then 50% of them discontinued the medication because of unacceptable side effects compared to if you had the long version of the allele. Now, there wasn't any difference in the mirtazapine group in terms of these alleles having an impact on discontinuation rates. And that makes perfect sense because mirtazapine doesn't go through the serotonin transporter to have its pharmacological effect, while paroxetine does, and so the allele frequency has an impact.

    They actually showed, in another study, where they were looking at the serotonin 2A receptor polymorphism, that if you combine a particular polymorphism of that and a promoter region polymorphism for the serotonin transporter, you actually had 70% of the patients discontinuing their treatment because of unacceptable side effects. Now, when you get to percentages like that, it's actually very important in terms of the translation of this to the clinical practice. Because if I have a 70% odds that somebody's not going to be able to tolerate the medication, I'm going to want to choose another medication because I want to be able to deliver the treatment to have a chance that the person will get better. And I'm unlikely to be able to do that.

    So, these are the kind of specific examples that we have had, where this level of knowledge is going to be so powerful. This is why research is so critical that includes ethnic diversity, because there are ethnic differences in terms of the serotonin transporter and the 5-hydroxytryptamine 2A (5-HT2A) polymorphisms that are also having an interaction in the allele.

    Dr. Satcher: Let me continue to integrate this discussion with the culture. It's interesting as you hear about all the things that we're learning about with medication that when it comes to the disparities in health, one of the concerns that we have â€' and it was pointed out by the Institute of Medicine's report â€' is that there are still disparities in the way patients are treated, seemingly on the basis of ethnicity. And, of course, the use of antidepressants is one of the examples that's been studied.

    So, at the same time as we're learning more and getting more technology, we also have to be aware of the fact that cultural issues still affect how people make decisions about diagnosis and treatment.

  • Slide 20. Paroxetine vs. Mirtazapine: Discontinuation Due to Adverse Events

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    Paroxetine vs. Mirtazapine: Discontinuation Due to Adverse Events

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  • Dr. Masand: Phil, another area which has been looked at in recent years is the response and remission rates with different classes of antidepressants. And Michael Thase presented a poster last week at the American Psychiatric Association (APA), looking at 45 controlled trials of venlafaxine vs SSRIs, showing differences in both response rate and remission rates. Tell us a little bit about that meta-analysis and, also, were there differences amongst the different ethnic groups?

    Dr. Ninan: That's a very interesting question and in a way, it's shameful that we don't have more information in this particular area. In the larger analysis that Thase presented last week at the APA, they have not actually looked at ethnic differences yet.

    But the previous version that was published that's called a pooled analysis has been looked at, and Richard Entsuah presented that recently. And what you have here is that when you're looking at response as the outcome measure, there's essentially no difference when you're looking at venlafaxine against the SSRIs as a group.

    But when you're looking at remission, what you find is that the remission rates that you have with the SSRIs don't seem to be as robust in the non-Caucasian group. But we have to be real cautious because there are only about 100 patients in that component of the study, while you have 1600 patients who are the Caucasian Americans who were involved in the rest of the study.

    So, we really do need to have more information available. And it's so critical for us to be able to get ethnic diversity in the populations that we are studying so that we can tell clinicians what is it that they should be doing. What are the odds, when you have a patient in front of you, that this particular treatment is going to result in a low burden of side effects and the achievement of remission?

    Dr. Masand: Although, Phil, we should point out to our audience that in the Caucasian sample, both in terms of response and remission, the patients on venlafaxine did significantly better than the SSRIs, both in the Entsuah analysis as well as Michael Thase's analysis.

    Dr. Ninan: That's correct.

  • Slide 21. Venlafaxine vs. SSRIs: Remission After Antidepressant Therapy

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    Venlafaxine vs. SSRIs: Remission After Antidepressant Therapy

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Ethical Issues

  • Dr. Masand: David and Phil, in this part of the program we usually address an ethical issue, an ethical dilemma that clinicians in the trenches struggle with.

    And I thought one of the issues that might be important and interesting to address is why isn't the diversity in our patient population reflected in the treatment teams that treat these patients, which then leads to a discrepancy in the care that is provided. And David, I wonder if you have some thoughts, having looked into this issue in great detail.

    Dr. Satcher: Well, it's interesting because if you go back to the 1970s and the 1980s, there was major momentum in this country toward increasing diversity in the health professions. The Association of American Medical Colleges (AAMC), of course, led that effort, and we made a lot of progress.

    That has tapered off significantly in recent years. In fact, there's been a decline. Dr. Sullivan recently headed up a study funded by Kellogg and the report is called the Sullivan Commission report. But basically, what it's showing is that when it comes to the health professions, diversity is not increasing, it's not keeping up with our population at all. And so we do need to refocus again.

    However, it's important for us to realize that we can't wait. We can't wait until we have adequate diversity among physicians and nurses and all those. We also have to make sure that we have teams that reflect that diversity.

    The Asian Counseling and Referral Center in Seattle, Washington, has really demonstrated this by taking a community, primarily Southeast Asians who spoke a lot of different languages â€' over 30 different languages â€' and they identified people in that community who could be trained to be a member of the healthcare team and dramatically improve the health seeking of that population in terms of mental health services, because there were people who spoke their language, understood their culture, and helped to train the professionals about how to deal with them. So, that's what we can do. We can make sure that we have teams that are culturally competent, even if we, ourselves, are not competent with all of these different cultures.

    Dr. Masand: Phil, there have been some hospitals, community mental health clinics that, in fact, have tried to achieve that diversity. And one example is in Jamaica Hospital, Queens, New York, where they have a specialized clinic for Asian Indian patients, which is staffed by Asian Indian physicians and nurses and other healthcare professionals. Is that something that is lacking in most communities around the country and, as a result, does it lead to care that may not be optimal for different cultural groups?

    Dr. Ninan: I think this is an issue that we all need to be aware of. I mean, if you have a population that, say, is in a very rural area, it's really not practical for us to be able to have all of the ethnic groups being represented.

    However, recognize the power of diversity, because I think that is so much a part of the strength of what America has. Because if you look at the rest of the world, there's a tremendous amount of tribalism and antagonism between ethnic groups that are maintained around national boundaries and issues like that. I think the United States is really so far ahead in terms of being able to assimilate diverse groups together, and to be able to bring it more as an acceptable form of multiculturalism.

    And the more we can get treatment groups, providers, being reflective of that ethnic diversity, the more comfortable the patients who are struggling with these illnesses will be in terms of being able to come forward with the problems that they're having, to be able to overcome the stigma, to be able to get the appropriate care so that they can achieve remission and be able to live their lives to their fullest potential.

    Dr. Satcher: And I think the national goal, one of the goals of Healthy People 2010 is the goal of eliminating disparities in health along different racial and ethnic groups. And I think it's an appropriate goal because, as Phil said, I think as a nation, we ought to be proud of our diversity and we ought to really build on it as a strength. And that's why that goal is so important, that we, in the healthcare profession, do everything we can to make sure that there are not disparities in health. And that they don't have anything to do with the quality of care that we provide to patients and that we can begin, then, to deal with lifestyle, environment, and the other things that contribute to disparities in health.

    Dr. Masand: That is so true, Phil and David, that America has really embraced diversity and begun to ask the kinds of questions that we are asking today to move the world forward in studying some of these areas. So, I think it's really something that would be a tremendous value to the world in terms of addressing some of these questions.

    We have Dr. Upton, who is one of our callers. Dr. Upton, welcome to the show.

    Caller: Thank you very much.

    Dr. Masand: What's your question for our faculty?

    Caller: Do you think psychiatrists' ethnicity should be listed on the various databases, Web sites that patients visit, to blindly select a psychiatrist? I've had several patients call me, blindly, and sometimes apologize before they asked if I was of a particular ethnicity because they wanted to see a psychiatrist of that ethnicity. And they had no way of determining that and sometimes I didn't know anybody, really, I could refer them to.

    Dr. Masand: Phil and David, that's an excellent question. And, you know, societies in the states, psychiatric societies, for example, will often ask you, when you fill out a questionnaire, whether you speak different languages, what kind of patients do you accept in your practice? Because as Dr. Upton points out, there are many patients who want to see somebody who they feel can relate to their culture. What's the best way to address that, David?

    Dr. Satcher: Well, it's interesting because I think I've lived through a period in this country where the listing of race was frowned upon because people were discriminated against because of their race. Not that they're not now, but I think that was the major concern then. Now the concern is how do we deal with the things that we've been talking about here today, racial and cultural differences? How do we make sure that we have the expertise that we need in the various areas?

    So, obviously, if someone did not want his or her race listed, I wouldn't do it. But certainly, if people are willing to have their racial identity listed, that becomes a resource for people seeking care, as long as people don't make judgments about people based on their race because there are some white physicians who are more sensitive, and vice versa, there are some black physicians more sensitive to some white patients in the profession. But that is a start to really know what you're dealing with.

    Dr. Masand: Phil, any kind of additional thoughts to Dr. Upton's question in terms of how does one go about making care broadly accessible?

    Dr. Ninan: The difference in terms of the kind of care, the kind of treatments, so psychotherapy vs pharmacotherapy, might also be an issue over here.

    So, for example, if you are going in for psychotherapy and the treating clinician has a psychoanalytic bend in the way they perceive an illness and you have somebody who's a patient who comes in who has a spiritual explanation for the distress that they're in. The Freudian approach vs the spiritual approach might be in disagreement or there might be issues there that the patient might have difficulty accepting. And so, some of these belief systems that provide the context in which you look at the meaning of symptoms is influenced so much by cultural beliefs and, therefore, might have a profound influence in terms of the optimal delivery of care.

    On the other hand, pharmacological treatment might be less of an issue. It's still an issue in terms of being able to make the appropriate diagnosis, to be able to understand the meaning of the idioms that the patient is using, and to be able to make the appropriate diagnosis and to be able to prescribe the appropriate medication, the starting dose, the therapeutic dose. How do you know that you got to remission, because the patient might not be using the terminology that we have in our Hamilton Depression Rating Scale because they have a different cultural background.

    Dr. Masand: Phil, that's a really good point because there was a recent poster at the annual meeting of the APA recently by Mark Zimmerman at Brown University, Providence, Rhode Island. And he asked a very interesting question; how should remission be defined? Should it be defined by a Hamilton score of less than 7 or less than 10? And so he asked patients, "How would you define remission in your lives?"

    And one of the interesting findings was, almost without fail, patients wanted to get back to their original level of functioning, to their original social interactions, to their original occupational level. And, as you rightly point out, that may be quite different for different cultures in terms of what is normal for them and what remission is for them.

    Dr. Ninan: That is correct.

    One of the fundamental issues that we struggle with, and it's a mainstream issue in psychiatry, is the absence of symptoms that allows you to achieve remission or the full potential; so the appropriate return of pleasurable pursuits rather than the absence of sadness. And those are issues that when you bring culture into these kind of questions can make it very, very complicated.

    Dr. Satcher: And then the other side of it, of course, is disability. And, you remember the World Health Organization looking at disability just in life-years, ranked mental illness as second only to cardiovascular disease and right above cancer as a cause of disability. But as you point out, disability varies from culture to culture. It's much more disabling, for example, to be blind in some cultures than in others.

    Dr. Masand: David, another good point is that disability is defined so differently in different cultures that, even for depression or for anxiety disorders, having social anxiety disorder may be quite different in Japan than it may be in South Korea or in Malaysia, for example.

    Dr. Ninan: That's right. That analogy, for example, that many Japanese patients with social anxiety describe feeling that they have offended those around them because they have an offensive smell. That's a very unusual presentation in the American situation, where people are much more individualistic and they seem to be less concerned about the social environment around them.

    Dr. Masand: There are a bunch of questions, so let's start with you, Phil. Dr. Michael Long writes, "Do you have any kind of data in terms of the acceptance of certain cultures to certain treatments for major depression? And more importantly, the acceptance of certain side effects, for example, sexual dysfunction or weight gain, are they differentially accepted by different cultures?"

    Dr. Ninan: Well, I think culture influences these issues. So, for example, weight and sexual functioning might have very different implications. In the Caucasian American population where perception is so much more important, weight can have profound influences. I saw this patient, for example, who said, "If I don't lose weight I can't imagine that I would not be depressed." She couldn't imagine that her depression would get better if she didn't lose weight. So that became the necessary step unless she was able to change that particular cognitive stance. So, each individual will have variation and then there are cultural influences that might manifest the acceptance of these potential side effects.

    Dr. Satcher: In some cultures, being overweight is considered to be attractive. And the same thing applies, of course, to sexual function. Recently, I believe, the Association for Research in Personality (ARP) presented a report where they had done a survey on attitudes towards sexuality. And it's amazing the variation in different populations in terms of what it means to have a sexual dysfunction. How important is sex in our life? People who sit up and watch TV, where sex is everything and every product is advertised using sex, probably think of sex quite differently than people who don't have that experience.

    Dr. Masand: David, it's interesting you mention that. Earlier this year I was in Malaysia, speaking to the Malaysian psychiatrists, and we kind of surveyed them as to what side effects of antipsychotic medications their patients were most concerned about. And it's interesting, in the US, weight gain is one of the most common reasons patients discontinue the antipsychotics. But in Malaysia, interestingly enough, sexual dysfunction was ahead of weight gain and you would have never expected that, counterintuitively, in a culture where sex and sexual dysfunction are not talked about. But they actually are affected by that.

    Here's a question for you, David, by Susan Murray, a nurse. She writes, "Do you know of any resources for educating the treatment team on cultural competency?"

    Dr. Satcher: There are now a few programs around the country. I mentioned the one at the Morehouse School of Medicine and it is open to people from outside. I believe there are 4 or 5 sessions a year where people come for 4 days. And I believe the University of Arizona, Tucson, Arizona, also has a training program.

    So, if you go on the web, you'll find training programs in cultural competency that can be used for individuals or groups. The AAMC certainly has information about the availability of those and probably the American Nursing Association, also.

    Dr. Masand: Terrific.

    Phil, a question from Jack Joiner; he emails us, "Are there any effects of Hispanic ethnicity on medication responsiveness?"

    Dr. Ninan: That's a very good question. There is a center in California that is exploring some of these issues. Unfortunately, what we find is that the variation in the dose that is prescribed by clinicians is a much greater variable than the average differences based on ethnic groups at this point. So, to be able to specifically answer that, we need to have fixed-dose studies in different ethnic groups. And those studies have not been published at this point.

    Dr. Masand: David, another question: "Are there differences amongst the genders within these cultural and ethnic groups?"

    Obviously, we are now kind of beginning to tease quite finely gender differences as well as cultural and ethnic differences.

    Dr. Satcher: Certainly gender differences are very important in psychiatry. Depression, we've talked about. Even though if you take the extreme, women are 4 times more likely to attempt suicide and men are much more likely to successfully complete suicide. It's really interesting in terms of that as being one measure of dealing with depression. So, there are differences by gender. We don't understand all of those differences in terms of how people experience depression.

    Obviously, things like postpartum depression are gender specific, and we're learning more and more about that every day. But being sensitive to how hormonal cycles as well as social issues impact differently upon different genders is very important.

    Dr. Ninan: And actually, African American women have the lowest rates of successful suicides. So, there's a complex interaction between gender, ethnicity, and all these vulnerability resilience kind of issues that are interacting at this complex level.

    Dr. Masand: Phil, I know some time ago there was some evidence that there may be gender differences in antidepressant response: Susan Kornstein's work showing that women did better with SSRIs compared to tricyclic antidepressants like imipramine. Has anybody looked at that in ethnic groups; for example, African American women vs Caucasian women? To your knowledge has anybody kind of broken it down by gender in terms of treatment response?

    Dr. Ninan: No, and that's a very good question because what we have here is a very complex interaction between anxiety vs depression. And then age and gender all interacting together and making some people more responsive to serotonergic drugs and other people more responsive to primarily noradrenergic drugs.

    To be able to answer that question, you would need to have a few hundred patients in each group, based on ethnicity and gender. We in psychiatry are excited when we do studies with 300 or 400 people. Cardiovascular disorders have thousands of patients in each study and we really need to get to that level of studies for us to be able to address these very critical issues.

    Dr. Masand: Phil, let's take this question. We showed a slide of venlafaxine producing higher rates of remission compared to the SSRIs in patients with major depression. And the question says to clarify again, that venlafaxine was superior to the SSRIs in producing remission in both Caucasians and non-Caucasians, not just in Caucasians. So, if you could just take us through the data.

    Dr. Ninan: When you look at the remission data, the statistical separation was seen, really, in the Caucasian population. The non-Caucasian population didn't have the statistical power, even though the numerical advantage was pretty similar to the Caucasian, because you had only about 100 patients in the non- Caucasian group.

    In terms of the response outcome, which is not a graphic that was shown in this presentation, you are able to show statistical separation in both the Caucasian and the non-Caucasian groups.

    So, this is an issue of statistical power and that's why we need larger studies with more diverse populations in them.

  • Slide 22. Ethical Issues

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    Ethical Issues

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Clinical Pearls

  • Dr. Masand: Thanks. Well, we had lots of wonderful questions. We didn't have a chance to get to some of the ethical dilemmas that we often address so, as we always do, David and Phil, we leave our audience with some clinical pearls, some take-home messages. And David, if I could begin with you to leave our audience with some clinical pearls regarding diagnostic issues as they relate to culture and ethnicity.

    Dr. Satcher: Well, I think it's really important when making a diagnosis of a mental health problem to put it into context of the patient's own culture. And, therefore, it's important to ask certain questions like, "What does this illness mean to you? What do you call it? What do you fear most about this illness? What is the greatest impact that it has upon you?" People talk about their illness from the standpoint of their culture. It's very important in making the right diagnosis but also in making the right treatment decision.

    Dr. Masand: David, what about some of the take-home messages to be trained in culture competency? You mentioned the CRASH concept as well as looking at patients as individuals, even given within an ethnic group.

    Dr. Satcher: Right. I would refer back to the CRASH approach to cultural competence in dealing with patients where the C reminds us to consider culture, the R to respect culture, the A to both assess and affirm culture in dealing with patients, the S also with a double meaning (sensitivity and self-awareness), and then finally, humility; all very important in dealing with patients as individuals.

  • Slide 23. Clinical Pearls

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    Clinical Pearls

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  • Dr. Masand: And then, finally Phil, we have just a couple of moments, what about some clinical pearls on management?

    Dr. Ninan: The critical issue in management, when we are talking about culture and ethnicity, is to recognize that culture is a very dynamic, changing phenomenon in today's world. And we have to recognize the meaning of symptoms when patients come in complaining about particular problems, and that the treatments that we provide, particularly psychotherapeutic treatments and now with the knowledge of pharmacogenomics and the pharmacological treatment, can influence the treatment and the outcome that we want to design.

    Dr. Masand: Thank you, David and Phil, for a wonderful discussion on a really important topic. And I want to thank you all for your wonderful questions and, unfortunately, we were not able to take all of them.

    I'm Dr. Prakash Masand, thanking you for joining us today and hoping that evidence will be your guide to patient care.

  • Slide 24. Clinical Pearls

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    Clinical Pearls

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