Cultural Aspects of the Pharmacological Treatment of Depression: Factors Affecting Minority and Youth

The cultural and demographic profile of the United States is undergoing a rapid transformation. In many areas of the country, there is no longer an ethnic majority but a multiplicity of racial and cultural groups. These changes can be attributed to 3 principal factors¹:

• The aging and lower fertility rates of the European origin population.
• The significant increase of immigration from developing countries, especially from Latin American and Asia.
• The higher fertility rates of the non-European minority groups.

Risk factors for depressive disorders in minority youth
The most recent studies reveal that minority children and adolescents are at a higher risk for depression than white youth. This is particularly true for Hispanic, non-Hispanic black, and American Indian youths.

Suicide rates, which have been traditionally lower among minority youth, are now equal to or surpass those of white youth. Hispanic, non-Hispanic black, and American Indian youth have a higher suicide risk than youth from the mainstream culture.

The stresses of living in poverty are frequently accompanied by variables such as discrimination, gender role pressures, losses related to immigration, and ongoing frustration and deficient support systems, which abound in this population.^2,3 Conflict also plays an important role in depression and often evolves into a vicious cycle in which irritability-a common feature of child and adolescent depression-increases interpersonal tensions and may cause parents, teachers, and friends to distance themselves from the depressed person. This, in turn, increases feelings of abandonment and lack of support.¹Evidence for disparities
Minority and immigrant children and adolescents face a number of barriers to effective mental health care. These include population barriers (socioeconomic disparities, stigma, poor health education, and lack of legal immigration status), provider factors (deficits in cross-cultural knowledge and skills and attitudinal sensitivity), and systemic factors (location of services and organizations, and lack of culturally competent services and practitioners).

Minority youth often reside in neighborhoods where services are unavailable, or they lack the public or private insurance necessary to obtain mental health services. Recent studies show that Hispanic families underuse mental health services because of language and cultural barriers,⁴ non-Hispanic black families underuse health services because of distrust,⁵ while Asian Americans avoid or delay seeking care because of the stigma that is associated with mental illness.⁶Diagnostic challenges
Diagnosing depression in minority and immigrant youths can be challenging to unfamiliar clinicians. There is significant evidence that psychiatric disorders are frequently misdiagnosed among culturally diverse youth. Various studies have found an overdiagnosis of conduct disorder and an underdiagnosis of depressive disorders in minority youths.^7-9 Misdiagnosis largely originates from difficulties that clinicians may have in addressing cultural differences, including cognitive biases stemming from stereotyping, lack of systematic assessment, and lack of contextualization of information obtained in diagnostic assessments.¹⁰ Most care for depression is provided by primary care physicians who may have relatively little experience with depression in children and adolescents and have added disincentives, such as decreased reimbursement for identifying a mental health versus a somatic health problem.¹¹

Children and adolescents from minority populations may demonstrate different symptoms than white American youths. Somatization and anger, for example, are symptoms more frequently associated with depression in minority youths.¹² The degree of emotional reactivity can also vary: Asian Americans who are depressed show heightened reactivity compared with white Americans who show less reactivity when depressed.¹³ Diagnosis is more challenging with depressed minority children and adolescents because of frequent comorbidities. For example, stresses associated with immigration, acculturation stress, discrimination, and community violence contribute not only to depression but also to anxiety, disruptive behavioral symptoms, substance abuse, and posttraumatic stress disorder (PTSD).^14-16

Kleinman¹⁷ argues that culture shapes the way individuals not only express but also understand the symptoms of illness. There are significant differences in how the various ethnic groups understand depression, which can influence help-seeking behaviors and invoke spiritual, supernatural, sociological, and interpersonal explanatory models. For example, non-Hispanic blacks often conceptualize depressive symptoms as part of their experience of sociopolitical oppression.¹⁸ Stigma also constitutes a major barrier to seeking mental health services in general, and cultural beliefs play a large role in the perpetuation of stigma. Many cultures have major negative associations with any type of mental health assistance, often equating this with serious psychopathology and social undesirability. The fear of double-stigmatization (being culturally different as well as "crazy") presents major barriers to accessing services.¹⁹

Kleinman¹⁷ developed the exploratory model, which methodically elicits the symptoms that are more salient and worrisome to the patient. This model helps reveal patterns of distress; explores perceived causes and attributions; identifies preferences in help-seeking behavior; helps uncover perceptions of stigma; and ultimately explores the discrepancies that may exist between the patient's understanding of the condition and the clinician's proposed etiology, diagnosis, and treatment plan. This model leads to higher levels of treatment adherence. Values are also intimately associated with levels of acculturation, generational differences, and educational and socioeconomic variables.

Understanding the differences between the values of traditional societies versus modern societies is an important tool that will help improve communication between the clinician and the patient (Table 1).It is also important to remember that a significant portion of immigrants and members of minority populations in the United States are urban or rural poor and that poverty and educational levels are important variables in determining the patient's understanding of illness and help-seeking behaviors.²⁰

 

Culture-bound syndromes are folk diagnostic categories that supply coherent meanings to certain recurrent and remarkable sets of experiences and observations. These are associated with the matter and forces that constitute the experienced universe and are often related to a particular culture's explanation of disease.²¹ There are multiplicities of culture-bound syndromes that tend to vary by geographical region.

Hispanic working-class women may sometimes have an attack of nerves that involves sighing or screaming loudly, falling on the floor, and losing consciousness. They often feel disempowered, helpless, and unable to protest or disagree with their husbands, senior family members, or authority figures. Having an "ataque de nervios" achieves the dual purpose of conveying to others that they have had enough, while at the same time arousing feelings of guilt in those thought to be responsible for this outcome. In addition, the ataque de nervios protects them from a direct confrontation, because the phenomenon is understood as being beyond the person's control.

There is a lack of consistency in the terminology of these syndromes, which has hindered efforts at classification. Thus, it may not be practical for clinicians to attempt to familiarize themselves with all of them. Instead, it is important to understand that symptom patterns are often linked and should be understood in their relationship to the particular cultural setting where they occur.

Table 2 presents recommendations that can be adapted by clinicians in diagnosing and treating psychiatric disorders in ethnic minority and immigrant patients.

Ethnopharmacology
The great advances in the technology of transportation that took place in the 19th and 20th centuries resulted in an increase in migrations worldwide. These migrations, in turn, are responsible for the enormous ethnic diversity that can now be found in countries such as the United States. The survival of any species depends, to a large extent, on its capacity to adapt to new and changing environments. So in nature, genetic polymorphism tends to be the rule rather than the exception. The new fields of ethnobiology and ethnopharmacology are rapidly gaining ground and, since 1999, the Surgeon General of the United States has mandated that ethnicity should be an important part of genetic studies.²²

Genetic polymorphism postulates that the number of genes controls the metabolism of drugs by affecting drug metabolizing enzymes, receptors, and transporters. Ethnopharmacology places its focus on the interethnic differences in pharmacokinetics and pharmacodynamics. Drugs are usually metabolized in 2 phases. In phase 1, metabolism occurs through the cytochrome P-450 (CYP) enzymes that lead to oxidation of the substrates. In phase 2, metabolism is through conjugation, which is mediated by the transferases. There is evidence of ethnic variations in both phases.²³

Differences in polymorphism in phase 1 that account for the variations in the CYP chain are responsible for the differences in how members of different ethnic groups metabolize drugs, leading to poor (ie, slow) metabolizers, who have decreased enzyme activity; and extensive metabolizers, who have increased activity, which occurs in ultrarapid metabolizers who have more than one copy of the gene on one or both alleles. Many of the psychotropic drugs are metabolized by CYP 2D6.²³

Receptors are also sensitive to genetic polymorphism and vary widely across ethnic groups. Enzymes, such as catechol-O-methyltransferase, responsible for metabolizing dopamine and monoamine oxidase, which, in turn, is responsible for metabolizing norepinephrine, are highly polymorphic. Genotyping of CYP 2D6 revealed a particular mutation that is found in approximately 34% of Asians.²⁴ This results in an enzyme with slower metabolic capacities than in white persons.The signal transduction cascade, composed of G-proteins, ion channels, second messengers, and protein kinases, is much less understood.²⁴

Another important consideration is that biological systems are dynamic, not static. The expression of genes is also influenced by variables such as environment, age and sex, nutrients, various plants and foods, steroid hormones, and other chemicals. For example, smoking, which is frequent among adolescents and is also highly comorbid with depression, may reduce serum concentrations of psychotropic medications by induction of CYP-1A2. This is a consideration that needs to be taken into account when medication is given to depressed adolescents who are also smokers. Grapefruit juice may increase serum concentrations of nefazodone, antivirals, and alprazolam by inhibiting CYP 3A4 (bioavailability is increased in the gut wall, and clearance is decreased in the liver).

The clinician prescribing psychotropic medications for patients of minority or immigrant backgrounds should first explore the presence of tobacco consumption, use of herbal remedies, and dietary habits of the patient before medicating, since these habits can influence the rate of metabolism of many psychotropic medications.This fact should be taken into account when treating adolescents from the Caribbean, who usually con- sume large amounts of citrus fruits. A high-protein diet, found among adolescents who practice athletic sports, accelerates the metabolism of certain CYP enzymes, and a diet high in carbohydrates, found in adolescents who may be sedentary and overweight, decreases the metabolism of certain CYP enzymes.²³

It is interesting to note that persons who migrate and leave behind the dietary habits of their country of origin begin to metabolize in a similar fashion as members of the new host country. For this reason, it is important to include in the clinical interview questions about whether the person is foreign-born or first- or second-generation American and how long they have been living in the United States.²⁴

Genotyping before medicating seems to be in the not too distant future. However, at present there are large gaps in phenotyping of the 4 major minority populations in the United States: Hispanics, non-Hispanic blacks, Asians, and American Indians.

Experience has shown that the practices of Western medicine have not eclipsed or replaced traditional medicine, but that the 2 are sometimes practiced simultaneously or sequentially among certain cultural groups. For example, a Navajo patient may visit the psychiatrist at the local community mental health center while simultaneously seeking help from a Navajo medicine man. In such cases, communication with the patient about these practices, and sometimes with the non-Western traditional practitioner, becomes important.Traditional remedies sometimes have strong active ingredients, such as atropinic substances that can produce anticholinergic adverse effects and even toxicity. Many patients do not inform their doctor that they are consuming these substances unless they are asked directly.

Hispanics present a challenge to psychopharmacology, since they are usually lumped together in a single ethnic category. Most Hispanics in the United States are a mix of Spaniards, Africans, and American Indians, who have descended from the Asian and Mongol people who crossed the Bering Strait and populated the American continent in pre-Columbian times. The J mutation of the CYP 2D6 is found in 47% to 70% of Asians and the Z mutation is found in 15% to 20% of non-Hispanic blacks. These mutations are responsible for slowing down the metabolism of compounds by CYP 2D6, including antibiotics, some cardiovascular medications, analgesics, and psychotropic medications.²⁵ These factors should be taken into account when prescribing SSRIs for non-Hispanic black adolescents as well as for Puerto Rican and Dominican adolescents who tend to have a large percentage of African ancestry.²⁶

Asians are frequent users of traditional medicines and many are slow metabolizers, due to polymorphism of the enzymesCYP 2C19, CYP 2D6, CYP 3A4, and possibly others that are still unknown. For these reasons, they sometimes perceive Western medicines as being too strong and as having too many adverse effects.²⁴

There has been little psychopharmacological research done with minority and immigrant youths using double-blind, placebo-controlled trials. The Treatment of Adolescent Depression Study had a 26% minority representation among its participants, and minority status was found not to be a significant moderator of acute outcome.²⁷ However, no separate data analysis on the efficacy of the treatments examined has been published. There are significant problems associated with inclusion of minority samples in research trials and with the identification and diagnoses of depression in minority children, which results in the lower numbers of youths who receive treatment for depression.^1,28

Many questions in this field remain unanswered, but what is clear is that ethnopharmacology has already become an important part of the psychiatric treatment paradigm.²⁹Psychotherapy
There are a number of evidence-based psychotherapeutic interventions that are gaining considerable research support for use with minority and immigrant children and youth. Cognitive-behavioral and interpersonal psychotherapies have some research evidence with Hispanic and non-Hispanic black youths.^30-32 Interpersonal psychotherapy was originally evaluated with a largely Hispanic sample³³ and was later shown to be more effective than cognitive-behavioral psychotherapy in a head-to-head trial,³⁴ lending some support to the importance of congruence between cultural values ("personalismo," the closer interpersonal relationships among Hispanics) and the effectiveness of psychotherapeutic interventions. School-based preventive interventions have also been used with minority children and adolescents. A school-based cognitive intervention for depression was found to be effective as long as 2 years ago.³⁵ Effectiveness was also shown using school-based cognitive-behavioral therapy for trauma-related depression or PTSD with Hispanic children and adolescents.³⁶

Some therapists have developed interventions that are specific for particular ethnic and racial groups, which have been evaluated for efficacy.³⁷ Group and family psychotherapy, particularly approaches that integrate cultural and ethnic identity themes, psychoeducation, and culturally consonant coping approaches, have also been reported as both well accepted and successful.

Conclusions
Culturally competent clinicians need to be aware and accepting of cultural differences and aware of their own culture and the biases it may create. In order to become more effective and to provide the best level of care for their patients, clinicians need to understand the cultural differences in the ethnic populations they serve and, based on this knowledge, to modify clinical approaches to the needs of their patients and families.

 

References:

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