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 ethnic 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 two 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, 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.
1. Lin KM, Poland RE. Ethnicity, culture, and psychopharmacology. In: Bloom FE, Kupfer DI, eds. Psychopharmacology: The Fourth Generation of Progress. New York: Raven Press; 1995.
2. Lin KM, Smith MW. Psychopharmacotherapy in the context of culture and ethnicity. In: Ruiz P, ed. Review. Ethnicity and Psychopharmacology. Washington, DC: American Psychiatric Association; 2000:1-36.
3. Miranda J, Chen D, Davis N, eds. Mental Health: Culture, Race, and Ethnicity: A Supplement to Mental Health: A Report of the Surgeon General. Rockville, MD: US Dept of Health and Human Services, Substance Abuse and Mental Health Services Administration, Center for Mental Health Services, NIH, National Institute of Mental Health; 2001.
4. Lin KM, Poland RE, Nakasaki G. Psychopharmacology and Psychobiology of Ethnicity. Washington, DC: American Psychiatric Press; 1993.
5. Kalow W. Pharmacogenetics of Drug Metabolism. New York: Pergamon Press; 1992.
6. Lin KM, Poland RE, Lau JK, Rubin RT. Haloperidol and prolactin concentrations in Asians and Caucasians. J Clin Psychopharmacol. 1988;8:195-201.
7. Guess HA, Kleinman A, Kusek JW, Engel LW, eds. The Science of the Placebo: Toward an Interdisciplinary Research Agenda. London: British Medical Journal Books; 2002.
8. Smith M, Lin KM, Mendoza R. “Non-biological” issues affecting psychopharmacotherapy: cultural considerations. In: Lin KM, Poland R, Nakasaki G, eds. Psychopharmacology and Psychobiology of Ethnicity. Washington, DC: American Psychiatric Press; 1993.
9. Julius RJ, Novitsky MA Jr, Dubin WR. Medication adherence: a review of the literature and implications for clinical practice. J Psychiatr Pract. 2009;15:34-44.
10. Kleinman A. Rethinking Psychiatry: From Cultural Category to Personal Experience. New York: Free Press; 1988.
11. Lewis-Fernández R, Díaz N. The cultural formulation: a method for assessing cultural factors affecting the clinical encounter. Psychiatr Q. 2002;73:271-295.
12. Pritchard JK, Rosenberg NA. Use of unlinked genetic markers to detect population stratification in association studies. Am J Hum Genet. 1999;65:220-228.
13. Spina E, Santoro V, D’Arrigo C. Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update. Clin Ther. 2008;30:1206-1227.
14. Zanger UM, Turpeinen M, Klein K, Schwab M. Functional pharmacogenetics/genomics of human cytochromes P-450 involved in drug biotransformation. Anal Bioanal Chem. 2008;392:1093-1108.
15. Kalow W, Meyer UA, Tyndale RF. Pharmacogenomics. 2nd ed. Boca Raton, FL: Taylor & Francis Group; 2005.
16. Ingelman-Sundberg M. Pharmacogenetics of cytochrome P-450 and its applications in drug therapy: the past, present, and future. Trends Pharmacol Sci. 2004;25:193-200.
17. Mendoza R, Wan YJ, Poland RE, et al. CYP2D6 polymorphism in a Mexican American population. Clin Pharmacol Ther. 2001;70:552-560.
18. Wan YJ, Poland RE, Han G, et al. Analysis of the CYP2D6 gene polymorphism and enzyme activity in African-Americans in southern California. Pharmacogenetics. 2001;11:489-499.
19. Luo H, Wan Y. Polymorphisms of genes encoding phase I enzymes in Mexican Americans—an ethnic comparison study. Curr Pharmacogenom. 2006;4:345-353.
20. Zhou C, Verma S, Blumberg B. The steroid and xenobiotic receptor (SXR), beyond xenobiotic metabolism. Nucl Recept Signal. 2009;7:e001.
21. Branch R, Salih S, Homeida M. Racial differences in drug metabolizing ability: a study with antipyrine in the Sudan. Clin Pharmacol Ther. 1978;24:283-286.
22. Lewis P, Rack PH, Vaddadi KS, Allen JJ. Ethnic differences in drug response. Postgrad Med J. 1980;56:46-49.
23. Lin KM, Lau JK, Smith R, et al. Comparison of alprazolam plasma levels in normal Asian and Caucasian male volunteers. Psychopharmacology (Berl). 1988;96:365-369.
24. Ajir K, Smith M, Lin KM, et al. The pharmacokinetics and pharmacodynamics of adinazolam: multi-ethnic comparisons. Psychopharmacology (Berl). 1997;129:265-270.
25. Sørensen JM. Herb-drug, food-drug, nutrient-drug, and drug-drug interactions: mechanisms involved and their medical implications. J Altern Complement Med.