Ethno-Psychopharmacology: Advances in Current Practice

Ethno-psychopharmacology, the psychiatric medicine subspecialty that addresses "cultural variations and differences ... influencing the effectiveness of prescription medicines used in the treatment of mental disorders," has made significant progress in the past two decades and now pre­sents intriguing new opportunities on the horizon, as emphasized in this volume. Twenty years ago, Keh-Ming Lin, one of this volume's coeditors, while reviewing the state of the emerging field of ethno-psychopharmacology research, noted the unresolved prevailing challenges at that time, including sample size, variations in pharmacological and pharmacokinetic properties of psychotropics, subcultural differences within each broadly defined ethnic group, lack of coordination among researchers from divergent settings, use of divergent research methodologies, and failure to assess the impact of nonpharmacological factors. He postulated, then, the need to clarify ethnic variations of pharmacokinetics and pharmacodynamics; to identify enzyme systems; and to identify the presence of genetically or environmentally determined factors, or both. New imaging techniques were emerging at the time, including SPECT, CTEEG, and newer and more direct assessment methods were stimulating fresh hope (1).

Now, 20 years later, this volume on ethno-psychopharmacology takes stock of the progress to date, focusing primarily on Asian patient populations—a timely choice, as Asia represents half of the world's population and few prior such studies have focused on this population—and with some reference to African-American and Hispanic populations.

Genetic, nongenetic, pharmacological, nonpharmacological, environmental, and nutritional factors are clearly and explicitly presented. Recent genetic and pharmacogenetic discoveries, such as genetic polymorphism and the encoding of receptors and transporter enzyme systems, coupled with the effects of nutrition factors as inducers or inhibitors; the elucidation of the role of cytochrome P450 and the differentiation of extensive metabolizers, poor metabolizers, intermediate metabolizers, and ultrarapid metabolizers, are opening new vistas regarding pharmacodynamics and pharmacokinetics.

Cytochrome enzymes CYP2D6, CYP3A4, CYP1A2, and CYP2C19 metabolize most psychotropics. Their clinical relevance is dramatically illustrated by genetic differences controlling these enzymes and resulting in marked variations among patient populations. A notable and clinically most relevant example is CYP2D6, with 50 mutations that directly affect the psychotropics' metabolism and are illuminatingly ethnic-specific. Examples of such clinically relevant and ethnically specific markers are CYP2D6*17, found in Africans, and CYP2D6*10, found in Asians. Both result in slower metabolism of CYP2D6 substrates (such as risperidone and paroxetine), thus developing higher plasma concentrations and requiring lower doses for therapeutic effect in this group of slow/poor metabolizers.

When the gene for the cytochrome enzyme CYP2D6 is duplicated or multiplied, as is often the case (as many as 13 copies), this duplication/multiplication phenomenon results in an increased number of enzymes available for metabolic processes, resulting in "ultrarapid metabolization." This occurs in 1% of Swedes, 5% of Spaniards, approximately 3% of Caucasian Americans, 19% of Arabs, and 29% of Ethiopians. These clusters will require higher doses of medications to achieve the therapeutic response. In prior scientific literature, this ultrarapid metabolization group was regarded as "noncompliant" because they did not respond to the standard medication doses administered. This, in hindsight, and in view of the recent ethnopharmacogenetic evidence, was a misnomer.

This fresh evidence provides researchers, educators, and clinical practitioners with updated models of complexity regarding drug, environment, genetic, social network, and cultural belief system interactions and with refined specificity for clinical pharmacologic interventions.

We live in a globalized world with significant population mobility and with abundant new opportunities for such research to grow and prosper and to compare ethnic populations in the Northern Hemisphere with those of their country of origin in the Southern Hemisphere, as well as across meridians, and to correct the disequilibrium of prior studies primarily focused on Caucasian subjects.

Ethno-Psychopharmacology: Advances in Current Practice challenges the reader also to envision further research possibilities in the genes, environment, social networks, culture, ethnicity, rituals and traditions, and transactions across the life cycle through systematic studies embedded in a biopsychosocial model that is standardized across participating centers. Such new undertakings, stimulated by the advances illustrated in this volume, are likely to enhance our scientific knowledge and the specificity of our clinical acumen, relieve suffering, improve the quality of life of those suffering from mental disorders, and renew psychiatric medicine's presence and valued contributions in the house of medicine.