with Napoleon Higgins, MD, William Bradford Larson, MD, PhD, Daniel Y. Cho, MD, and Rahn K. Bailey, MD

Ethnopsychopharmacology seeks to understand the ways in which medications and their outcomes are influenced by the complex interactions of genes, environment, and culture. It is important to be aware of the role that ethnicity plays in psychiatric pharmacological treatment, as it may affect patient outcomes differently across specific groups.

Napoleon Higgins, MD, a psychiatrist in the Houston area and founder of Bay Pointe Behavioral Health Services, so introduced the symposium on the topic at the American Psychiatric Association annual meeting, held online May 1-3, 2021. “Because minority groups are underrepresented in the drug development process, we need a clearer picture of how different medications may affect subsets of our populations,” Dr. Higgins told the audience before introducing Dr. Larson, the symposium chair.

William Bradford Larson, MD, PhD, associate dean for disparities at the University of Texas at Austin Dell Medical School, and a leading pioneer in the field of ethnopsychopharmacology, spoke about considerations relating to the pharmacokinetics and pharmacodynamics of various medications, as well as cultural and social factors that contribute to varied clinical outcomes of ethnic populations.

According to Dr. Larson, numerous factors underlie the mechanisms by which drugs are metabolized by people of different ethnic groups. He pointed to a few classic examples, such as  the distinctive facial flushing experienced by some East Asians after consuming alcohol. Some African Americans experience hemolysis following primaquine administration because of a deficiency in the G6PD enzyme. In Southeast Asian populations, carbamazepine-induced cutaneous adverse drug reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are strongly associated with the HLA-B*1502 allele.

Panelists discussed how the metabolism and diet of people belonging to different ethnic groups may impact their medication response and how biases may act as a barrier to obtaining adequate mental health care among some patient population groups.

Genetic Effects on Medication – Pharmacokinetics & Pharmacodynamics

Ethnic differences in allele expression of subsets of cytochrome P450 affect the metabolism of at least 30 psychotropic medications. Such differences encompass enzyme inhibition, induction, genetic polymorphism, or duplication in coding regions of these enzymes.

  • Poor metabolizers may be defined as having two inactive or deficient alleles, which may lead to higher blood levels of a drug and more severe side effects.
  • Ultrarapid metabolizers may have three or more active alleles, leading to low drug levels in their bodies; their symptoms may falsely resemble treatment-resistant psychiatric disease.

Both psychotropic and non-psychotropic medications may be metabolized at different rates in different ethnic groups.

For example, 29% of the Ethiopian population has been found to have duplicated active genes for CYP2D6 compared to 15% of Arabs and 1% to 2% of other Black, Asian, or European populations.1 In contrast, 7.7% of Caucasians are poor metabolizers due to mutant alleles of CYP2D6, with 25% exhibiting mutant alleles of CYP2D6*4.2

Psychotropic drugs such as risperidone, haloperidol, thioridazone, oxycodone, and SSRIs may be metabolized differently by different ethnic groups, especially if used in combination with other drugs metabolized by CYP2D6*4. A prime example of such an interaction occurs when women taking tamoxifen for breast cancer treatment are also prescribed an SSRI for depression. Some SSRIs inhibit the metabolism of tamoxifen to its more active metabolites by the CYP2D6 enzyme, thereby decreasing the anticancer effect.3

More on using pharmacogenomics to optimize opioid drug therapy and to initiate antidepressants and antipsychotics in patients with comorbid pain and mental health disorders on our sister site PPM.

Cultural Variations in Diet and Medication Response

Cultural variations in diet also impact pharmaceutical efficacy by their effect on CYP450 enzymes. Cruciferous vegetables, such as broccoli, cauliflower, and cabbage, are CYP inducers, for instance. Smoking food or using charcoal in cooking also induce CYP450 enzymes. Coffee, corn, carrots, and citrus fruits, especially grapefruits, are CYP450 inhibitors, as are Indian spices used in South Asian cooking, such as cinnamon, cardamom, and black pepper.4

Neuroleptic Metabolism in Different Ethnic Groups

Daniel Y. Cho, MD, a psychiatrist in Charleston, West Virginia, spoke about the effects of specific neuroleptics – a class of antipsychotics used to treat psychosis and schizophrenia – on individuals of various ethnic groups. Specifically, he observed that the average prescribed dose of neuroleptics varies from country to country, but clinical symptoms decrease even in countries using lower doses. He hypothesized that differences in population genetics were the cause and characterized the above-mentioned phenotypes even further into these three groups:5

  • extensive metabolizers have two wild-type functional alleles
  • intermediate metabolizers have two reduced functional alleles or one null allele and a functional allele
  • poor metabolizers have two non-functional alleles.

Dr. Cho shared examples from the literature showing that differences in alleles have a significant effect on drug metabolism. The number of alleles a person has can affect plasma drug concentrations as well as drug side effects – not only in psychiatric medications, but also in pain medications and cancer treatments. In one study, after receiving 0.4 mg/Kg of haloperidol daily for 6 weeks, plasma levels of the drug were 52% higher in subjects of Chinese ethnicity (in Peking) with schizophrenia than in non-Asian subjects in the United States.6 For tricyclic antidepressants (TCAs), as well as diazepam and citalopram, people with two unique polymorphisms of CYP2C19 were demonstrated to have poor metabolism, with one of the two found almost exclusively in East Asians.7

In a classic study of the differential effects of amitriptyline and its metabolite nortriptyline in 65 Black and white patients undergoing treatment for depression, there were no differences in the rate of demethylation of amitriptyline to nortriptyline or in steady-state amitriptyline levels based on race. However, in the nortriptyline treated group, Black patients had plasma levels that were 50% higher than those in white patients.8 These decreased rates of metabolism in Black patients may result in increased side effects and treatment failure if the therapeutic plasma range is exceeded, explained Dr. Cho.

See also, how pharmacogenetic testing can help to target depression treatment with personalized antidepressants.

Studies have shown that East Asians respond to lower doses of lithium, with correspondingly lower blood levels, than do Caucasians.9 Studies have been mixed on the exact gene polymorphism responsible for these differences, but recent findings underscore the genetic contribution to lithium response in bipolar disorder and support the emerging concept of a lithium-responsive biotype.10

Different Comorbidities Seen in Minority Populations

Rahn K. Bailey, MD, chair and professor of psychiatry at Meharry Medical College in Nashville, spoke about biological and cultural differences that can impact the mental health care of ethnic populations. For example, certain minority populations, including African Americans, Hispanic Americans, and Asian Americans, suffer increased rates of obesity or diabetes compared to white Americans. Other groups have increased rates of smoking, which can impact drug metabolism.

Dr. Bailey advised that these predispositions must be taken into consideration when choosing the optimum antipsychotic to administer. Antipsychotics are known to increase the risk of diabetes, most likely the result of their effect on weight gain and insulin resistance, but also because of genetic, cultural, and lifestyle influences.11

While psychiatrists generally are not involved in the general medical care of patients, they do have an opportunity to prevent early mortality by being aware of and screening for a patient’s comorbidities, such as diabetes and cardiovascular disease, and prescribing an antipsychotic with a lower metabolic risk when appropriate.11 Collaborating with the patient’s primary care physician or specialty care physician may also be beneficial.

More on integrating mental and physical health in our special report.

Social Bias in Seeking Mental Health Care: The Need for Cultural Humility

Different ethnic groups in the United States have varying attitudes toward seeking psychiatric care and starting treatment, especially when it comes to medication, explained Dr. Bailey. For example, “Many Black Americans are described as being noncompliant with their treatment, but in actuality, they may be experiencing side effects or a lack of effect because of their phenotype. They may be blamed for the lack of effect, thereby increasing hostility between patient and clinician,” he told the attendees.

Black Americans tend to be more likely than white Americans to seek mental health care from primary care physicians, he continued. “In many communities of color, ‘real doctors’ physically touch their patients to examine them. Because psychiatrists do not physically examine their patients, Black patients may not believe they are real doctors. As a result, they are less likely to seek psychiatric care and be prescribed psychiatric medications.”

Black Americans and Hispanic Americans may experience longer courses of mental illness and greater disability as a result of such cultural beliefs (see our consumer report on schizophrenia in Black Americans). They may minimize their symptoms because they do not want to seek treatment from a psychiatrist.12 When they do, they may follow drug recommendations, but not other recommendations regarding diet, alcohol use, and other lifestyle measures.

Social bias related to mental health care is a significant factor for many Black, Indigenous, and People of Color (BIPOC). “They may not always have an accurate idea of what psychiatric treatment is and the benefits treatment can provide, said Dr. Bailey. For example, someone who had symptoms of ADHD as a child but outgrew them to become a functional adult may question whether their child with similar symptoms really needs ADHD treatment.

Socioeconomic disadvantages among BIPOC communities, such as decreased access to care, may further prevent them from seeking or obtaining appropriate mental health care.12 “Black adults in the US are more likely than white adults to receive mental health services from a mental health provider other than a psychiatrist, such as a social worker or counselor. In addition, Black adults and other people of color with a substance use disorder (SUD) are more likely to receive a single diagnosis instead of multifaceted results. Compared to white adults, Black adults with co-occurring mood or anxiety disorders and substance use disorders are significantly less likely to receive services for the mood or anxiety disorders,” concluded Dr. Bailey.

More on these disparities and the importance of cultural humility with Dr. Steven Starks.

Last Updated: May 27, 2021