Cultural and Ethnic Issues in Psychopharmacology

Environmental factors that affect pharmacological response

The regulation of the expression of CYP3A4 provides an illuminating example of how environmental factors exert significant influences on this and other enzymes that contribute significantly to drug metabolism. CYP3A4 is responsible for the metabolism of many antidepressants, benzodiazepines, antibiotics, immunosuppressants, and antiviral agents.^13,14 It has long been known that the gene encoding the enzyme is highly responsive to environmental influences that can lead to drug-drug, nutrient-drug, and medicinal herb-drug interactions.

Grapefruit juice and red wines have long been known to inhibit the activity of the enzyme, which can lead to potentially lethal toxicity with immunosuppressants and antivirals and to oversedation with benzodiazepines and nefazodone(Drug information on nefazodone).

On the other hand, St John’s wort dramatically induces the production of CYP3A4, which causes drugs to break down at a faster rate and dramatically reduces their concentration in the blood and the brain. The result may be reduced effectiveness and symptomatic relapse. The mechanism for such induction involves the steroid and xenobiotics receptor (SXR) involved in the regulation of the metabolism of steroids and phytochemicals. The SXR binds to the promoter region of the CYP3A4 gene and regulates its transcription. As the name implies, the SXR is activated by a wide range of foreign substances, including manufactured drugs, medicinal herbs, nutrients, and environmental toxins. In addition to CYP3A4, the SXR regulates a number of other drug-metabolizing enzymes and membrane protein transporters, and it serves as the master key for speeding up metabolism when the organism is exposed to potentially harmful foreign substances.²⁰

Dietary practices and the use of medicinal herbs vary widely across cultural groups, which represents another major reason for variations in drug responses across ethnic and cultural populations. For example, the metabolism of drugs such as antipyrine and clomipramine(Drug information on clomipramine) is significantly slower in Sudanese people and South Indians while they reside in their native countries; however, when they immigrate to Western countries and gradually adapt to the diet of the host society, their metabolism of these drugs speeds up and reaches levels found in white populations.^20,21 Similar mechanisms may be responsible for observed differences in the metabolism of alprazolam(Drug information on alprazolam), adinazolam, and clomipramine across populations. East Asians and Asian Americans metabolize these agents more slowly than do their white counterparts, probably a result of environmental rather than genetic factors.^22-24

Dietary differences and the use of medicinal herbs also vary significantly in different regions of the world and across different ethnic and cultural groups. Many medicinal herbs are potent inhibitors or inducers of CYP enzymes, which may also contribute toward observed cross-ethnic and cross-cultural variations in drug metabolism.²⁵

Summary

This article aims to provide a glimpse of recent developments that are relevant to cultural and ethnic influences on psychopharmacological responses. Instead of considering these influences as just factors of peripheral significance, they should be regarded as central in determining the success of treatment interventions. These factors crucially influence both the symbolic and instrumental dimensions of pharmacological effects.

Neglect of these issues can lead to miscommunication, distrust, medication nonadherence, diminished placebo response, and treatment failure. On the biological side, it is clear that culture and ethnicity determine both pharmacokinetic and pharmacodynamic processes, and hence the propensity for adverse effects and the likelihood of specific pharmacological effects. Both of these processes are genetically and environmentally determined.

While pharmacogenomics as a field is starting to show great promise in enabling us to predict both cross-ethnic and interindividual variations in treatment responses, the goal of individualized or personalized pharmacotherapy may be a number of years off. Nevertheless, the awareness of such variations will go a long way toward optimizing pharmacotherapeutic gains. Tools such as DSM-IV-TR cultural formulation guidelines should prove extremely useful in providing the foundation for such benefits to take place. As shown in Figure 2, simultaneous attention to the cultural and biological aspects of pharmacotherapeutic responses as well as to their interactions is crucial and indispensable.