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
As shown in Figure 1, genes control both pharmacokinetic and pharmacodynamic processes. Genetic variations fundamentally affect both processes and are responsible for both cross-ethnic and interindividual differences in drug response. At the same time, the expression of these genes is often influenced by environmental factors, such as diet and exposure to other substances, as well as by factors that are significantly influenced by the sociocultural milieu of the patient.13,14
Cytochrome P-450 2D6 (CYP2D6) may represent the best clinically significant example of ethnic variations at the genetic level. Since CYP2D6 participates in the metabolism of close to 50% of the drugs currently on the market, genotypic and phenotypic variations of the enzyme often lead to major differences in the concentration of the drugs in the blood and the brain. The result is a remarkable divergence in therapeutic responses and propensity for adverse effects.1,2,12,13
CYP2D6 has more than 50 distinct variant alleles that lead to the production of enzymes with divergent activities and that effectively divide patients into 4 groups:
• Poor metabolizers have 2 defective genes and the complete absence of CYP2D6
• Slow metabolizers have variant genes that are less effective in producing the enzyme
• Extensive metabolizers have 2 functional “wild-type” genes
• Ultra-rapid metabolizers have more than 2 copies of the gene and excessive production of the enzyme
As is true with the majority of the genes that have been studied, these CYP2D6 genotype groups are highly unevenly distributed across ethnic and racial groups. Although the majority of whites of European ancestry are extensive metabolizers, 5% to 9% are poor metabolizers because of the existence of a specific allele labeled as CYP2D6*4. By contrast, up to 70% of patients with East Asian ancestry carry another distinct allele (CYP2D6*10) that produces a less effective form of the enzyme, which makes many of them slow metabolizers. Caused by yet another specific allele (CYP2D6*17) commonly seen only in those of sub-Saharan African origin (20% to 40%), African Americans and sub-Saharan Africans also are more likely to be slow metabolizers. Ultra-rapid metabolizers are highly prevalent among Ethiopians (29%), Arabs (19%), Ethiopian and Sephardic Jews (18% and 13%), and people from southern Spain (5%), but they are relatively rare (less than 1%) in other populations.15-19