Cultural and Ethnic Issues in Psychopharmacology

Since the inception of the modern era of psychopharmacology, psychotropics have been the mainstay of the care of psychiatric patients all over the world, irrespective of their cultural and ethnic backgrounds. Until recently, however, variations in treatment response across populations, including effectiveness, dosing strategies, and adverse-effect profiles, have received minimal attention.^1,2

Psychopharmacological research in general and randomized controlled trials in particular have been conducted largely in North America and Western Europe and have rarely included persons of ethnic minority or cross-cultural backgrounds.³ This, in part, reflects the asymmetrical distribution of resources and the “Eurocentric” slant of the research establishment. Responsibility for such biases also lies in deeply rooted beliefs and assumptions that suggest that treatment responses are predominantly determined by biological mechanisms and that biological processes are universally applicable and thus color- and culture-free.

In contrast, there have been remarkable changes in the past 3 decades in the documentation of often substantial variations in drug responses across cultural and eth-nic groups and in the delineation of mechanisms responsible for the variations.^4,5 These findings have profound clinical and theoretical import, and it is important that they not be simplistically interpreted. As is true with all social and biological phenomena (eg, height, weight, temperament, child-rearing practices), drug response characteristics are normally distributed so that between-group differences are always accompanied by overlaps at the individual level.

Remarkable interindividual and intracultural variations coexist with ethnic/cultural differences. That is, while the majority of members of a population group fall on one side of the distribution, and those of another group on the other side, there are always exceptions. Neglect of such overlaps may lead to overgeneralization of research findings, which, in turn, could contribute to cultural stereotyping and consequent stigmatization.

For example, there are substantive ethnic variations in haloperidol metabolism between Asians and whites.⁶ At the same time, equally extensive interindividual variations within each of the ethnic groups also have been seen, resulting in significant overlap between the 2 groups.

This article reviews the cultural and biological aspects of drug effects and the role of interindividual, cross-ethnic, and genetic variations as well as environmental factors on treatment response.

Cultural aspects of drug effects

For the purposes of clarity in discussion, materials and opinions included in this article are presented with concepts that are commonly regarded as dichotomous in nature, such as culture and biology, as well as the “instrumental” versus “symbolic” aspects of pharmacological responses. In reality, increasing evidence indicates that such divisions are artificial and potentially misleading. In many instances, culture and biology clearly interact with and influence each other, as do medications’ “instrumental” (biological, pharmacological) and “symbolic” (nonbiological) effects. For example, drug-induced sedation may be regarded by one patient as a positive sign that suggests that the medication is beginning to work. For another patient, it may be an alarming sign of symptomatic worsening or a harbinger of medication toxicity. Such interpretations, based on individual beliefs that have been shaped largely by cultural and personal backgrounds, serve to further influence subsequent treatment response.

Keeping these caveats in mind, one of the most important issues that should be emphasized in any pharmacotherapeutic endeavor is that, however defined, the power of the symbolic aspect of treatment response typically outweighs instrumental effects of medications. It is for this reason that double-blind, randomized controlled trials are indispensable for the evaluation of the effectiveness of any intervention. In most clinical trials, placebo effects are seen in 30% to 50% of participants. New drugs usually need to show an additional 10% to 20% efficacy over placebo response to be approved for marketing and clinical use.

Placebo effects are largely determined by the patient’s expectations and beliefs, which are not only responsible for most of the therapeutic effects of treatment but can also lead to significant adverse effects.

The power of placebo response, mediated via symbolic mechanisms, is generally believed to be the basis for the popularity and effectiveness of most indigenous healing practices and alternative-treatment approaches. Thus, even if their instrumental properties are minimal as generally assumed, they could still provide therapeutic benefits that are substantive and at times dramatic. Embedded in patients’ sociocultural milieus, and often congruent with their beliefs and views on health and illness, such healing practices foster hope and expectations of recovery, thereby maximizing placebo response. Contrary to general belief, placebo responses are often accompanied by physiological changes (eg, changes in blood pressure, neurohormonal levels, brain imaging characteristics) that are indistinguishable from those seen with active pharmacological agents.⁷

In contrast, contemporary biomedical practices typically focus exclusively on the instrumental aspects of pharmacological effects. By downplaying or minimizing the symbolic aspect of medication effects and by regarding placebo responses as unreal and perhaps unworthy of scientific attention, clinicians can miss the opportunity to garner the power of the most important therapeutic element in patient care, which may not be easily compensated by their scientifically based professional knowledge and technical prowess.

To maximize therapeutic responses, general agreement in the expectations and beliefs between clinicians and patients is crucial. Without such agreement, it is hard to establish trust and to foster a trajectory for the anticipation of improvement. Where health beliefs diverge-as often is the case between Western-trained clinicians and patients imbued with traditional concepts of health and illness (which are surprisingly common and tenacious, even among the highly educated)-the treatment offered is not likely to be useful, no matter how powerful the instrumental effects are of a medication. In this sense alone, ignorance or neglect of patients’ culturally shaped health beliefs and expectations often guarantees therapeutic failure.

Equally or perhaps more important is that mismatches in beliefs and expectations between clinicians and patients often lead to a breakdown of clinician-patient communication, as well as treatment discontinuation and nonadherence.⁸ Even in situations where cultural differences between clinicians and their patients are not obvious, medication nonadherence is often highly prevalent. In patients with chronic conditions (eg, diabetes, hypertension, and most psychiatric disorders) who require long-term medication use, the rate of nonadherence could be expected to exceed 50%.⁹ When compounded by cultural communication gaps, as is often the case when patients of ethnic minority or cross-cultural backgrounds enter treatment programs, failure in medication adherence could be expected to be the norm rather than the exception.

The principles for bridging these gaps, for minimizing nonadherence, and for maximizing the symbolicside of medication effects appear deceptively simple but have been hard to implement. In large measure, this is the result of an almost exclusive reliance of modern medicine (and psychiatry) on biological reductionism and technological fixes, ignoring the contextual treatment and healing, which are predominantly mediated via symbolic means. Recent advances in medical anthropology, cultural psychiatry, and related fields have led to the development of specific approaches that aim to remedy these problems.

Treatment in an age of cross-cultural diversity

As contemporary biomedical theories and approaches become increasingly sophisticated, they become progressively more difficult for patients and the general public to comprehend. At the same time, through the long process of training, clinicians adopt views and attitudes that progressively diverge from those held by many of their patients. Backed by knowledge and insight derived from scientific investigations and simultaneously pressured to establish and maintain their professional identities, as well as to convey the appearance of confidence and authority (also essential for fostering placebo responses), clinicians often become detached from the fact that profound uncertainties are, and always will be, inherent in clinical situations, thereby failing to appreciate elements of plausibility in the interpretations and concerns of their patients and family members.

Therefore, a relativistic position should be considered to minimize these problems. Such a position can afford the clinician an opportunity to better understand the patient’s personal, social, and cultural world. Better communication and increased trust will lead to greater patientsatisfaction and better adherence to treatment.¹⁰

In order to achieve these goals, a systematic approach is essential; clinical assessments should routinely include the elicitation of patients’ perspectives on the following:

• The possible causes of the illness

• Modes of onset

• Illness course

• Beliefs about the outcome

• Name or label for the problem(s)

• Range of available treatment options and the expectation of the effectiveness of these interventions, both indigenous/alternative and biomedical

DSM-IV-TR cultural formulation guidelines help accomplish this task. The model (when used appropriately) yields crucial information regarding the patient’s idioms of distress, illness categories, past experiences in seeking help, expectations regarding current encounters with the health care system, and reactions to recommended medications. Applied in clinical settings, cultural formulation guidelines should improve clinicians’ ability to more effectively formulate treatment plans, thereby enhancing the patient-clinician alliance and hence therapeutic response-both pharmacological and alternative.¹¹

Interindividual and cross-ethnic variations

As early as the 1950s, substantial cross-ethnic and interindividual variations in psychotropic responses had been identified. Such variations have remained mostly obscure, however, because many of the reports were published in nonclinical journals.^1,2,4,5 Pharmacogenetics as a discipline has its origin in observations of severe adverse effects, which vary dramatically across ethnic groups.^1,6 Subsequently, when major enzymes (such as a number of the cytochrome P-450 isozymes) responsible for the metabolism of psychotropic and other medications were identified, it became clear that there are substantial ethnic variations in enzyme activity.

More recently, studies aimed at identifying genetic determinants of disease susceptibility, temperament, and behavioral traits have led to the discovery of genetic variations that affect psychotropic responses. The gene that encodes the serotonin (5-HT) transporter and the enzyme catechol-O-methyltransferase serve as the most prominent examples. Since almost all of the alleles that affect the activity of such genes are unevenly distributed across ethnic groups, subsequent human genomic studies have been compelled to take ethnicity and race into serious consideration.¹²

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