Abstract
Current pharmacotherapies for psychiatric disorders are generally incompletely effective. Many patients do not respond well or suffer adverse reactions to these drugs, which can result in poor patient compliance and poor treatment outcome. Adverse drug reactions and non-response are likely to be influenced by genetic polymorphisms. Pharmacogenetics holds some promise for improving the treatment of mood disorders by utilising information about genetic polymorphisms to match patients to the drug therapy that is the most effective with the fewest side effects. Pharmacogenomics promises to facilitate the development of new drugs for treatment. However, these technologies raise many ethical, economic and regulatory issues that need to be addressed before they can be integrated into psychiatry, and medicine more generally. We discuss ethical and policy issues arising from pharmacogenetic testing and pharmacogenomics research, such as informed consent, privacy and confidentiality, research on vulnerable persons and discrimination; and economic viability of pharmacogenetics and pharmacogenomics. We conclude with recommendations for the regulation and distribution of pharmacogenetic testing services and pharmacogenomic drugs.
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References
Thase ME, Rush AJ (1997) When at first you don’t succeed: sequential strategies for antidepressant nonresponders. J Clin Psychiatry 58:23–29
Pickar D, Rubinow K (2001) Pharmacogenomics of psychiatric disorders. Trends Pharmacol Sci 22:75–83
Steimer W, Muller B, Leucht S, et al (2001) Pharmacogenetics: a new diagnostic tool in the management of antidepressive drug therapy. Clin Chim Acta 308:33–41
Wolf CR, Smith G, Smith RL (2000) Science, medicine, and the future: pharmacogenetics. BMJ 320:987–990
Chen S, Cho W-H, Blouin RA, et al (1996) The cyochrome P450 2D6 (CYP2D6) enzyme polymorphism: screening costs and influence on clinical outcomes in psychiatry. Clin Pharmacol Ther 60:522–534
Issa AM (2000) Ethical considerations in clinical pharmacogenomics research. Trends Pharmacol Sci 21:247–249
Lindpaintner K (2002) The impact of pharmacogenetics and pharmacogenomics on drug discovery. Nat Rev Drug Discov 1:463–469
Lindpaintner K (2003) Pharmacogenetics and the future of medical practice. J Mol Med 81:141–153
Issa AM (2002) Ethical perspectives on pharmacogenomic profiling in the drug development process. Nat Rev Drug Discov 1:300–308
Kirchheiner J, Brosen K, Dahl ML, et al (2001) CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages. Acta Psychiatr Scand 104:173–192
Lerer B, Macciardi FM (2002) Pharmacogenetics of antidepressant and mood-stabilizing drugs: a review of candidate-gene studies and future research directions. Int J Neuropsychopharmacol 5:255–275
Mancama D, Kerwin RW (2003) Role of pharmacogenomics in individualising treatment with SSRIs. CNS Drugs 17:143–151
Serretti A, Artioli P (2003) Predicting response to lithium in mood disorders: role of genetic polymorphisms. Am J Pharmacogenomics 3:17–30
Robertson JA, Brody B, Buchanan A, et al (2002) Pharmacogenetic challenges for the health care system. Health Aff (Millwood) 21:155–167
Melzer D, Raven A, Detmer DE, et al (2003) My very own medicine: what must I know? Cambridge, Cambridge University Press
Rothstein MA, Epps PG (2001) Ethical and legal implications of pharmacogenomics. Nat Rev Genet 2:228–231
Hurko O (2001) Genetics and genomics in neuropsychopharmacology: the impact on drug discovery and development. Eur Neuropsychopharmacol 11:491–499
Arranz MJ, Munro J, Osborne S, et al (2001) Applications of pharmacogenetics in psychiatry: personalisation of treatment. Expert Opin Pharmacother 2:537–542
Horrobin DF (2001) Realism in drug discovery-could Cassandra be right? Nat Biotechnol 19:1099–1100
Johnson JA, Evans WE (2002) Molecular diagnostics as a predictive tool: genetics of drug efficacy and toxicity. Trends Mol Med 8:300–305
Poolsup N, Li Wan Po A, Knight TL (2000) Pharmacogenetics and psychopharmacotherapy. J Clin Pharm Ther 25:197–220
Sadee W (1999) Pharmacogenomics. BMJ 319:1–4
Catalano M (1999) The challenges of psychopharmacogenetics. Am J Hum Genet 65:606–610
Schmitz G, Aslanidis C, Lackner KJ (2001) Pharmacogenomics: implications for laboratory medicine. Clin Chim Acta 308:43–53
Buchanan A, Califano A, Kahn J, et al (2002) Pharmacogenetics: ethical issues and policy options. Kennedy Inst Ethics J 12:1–15
Ensom MHH, Chang TKH, Patel P (2001) Pharmacogenetics: the therapeutic drug monitoring of the future? Clin Pharmacokinet 40:783–802
Meyer UA (2002) Introduction to pharmacogenomics: promises, opportunities, and limitations. In: Licinio J, Wong M-L (eds) Pharmacogenomics: the search for individualized therapies. Wiley-VCH, Los Angeles, pp 1–8
Beauchamp TL, Childress JF (2001) Principles of biomedical ethics. Oxford University Press, Oxford
Brody BA (1998) The ethics of biomedical research: an international perspective. Oxford University Press, Oxford
Nebert DW, Bingham E (2001) Pharmacogenomics: out of the lab and into the community. Trends Biotechnol 19:519–523
Robertson JA (2001) Consent and privacy in pharmacogenetic testing. Nat Genet 28:207–209
Moldrup C (2001) Ethical, social and legal implications of pharmacogenomics: a critical review. Community Genet 1:204–214
Vaszar LT, Rosen GD, Raffin TA (2002) Pharmacogenomics and the challenge to privacy. Pharmacogenomics J 2:144–147
Anderson DC, Gomez-Mancilla B, Spear BB, et al (2002) Elements of informed consent for pharmacogenetic research: perspective of the pharmacogenetics working group. Pharmacogenomics J 2:284–292
Thomas SM (2001) Pharmacogenetics: the ethical context. Pharmacogenomics J 1:239–242
Fuller BP, Kahn MJ, Barr PA, et al (1999) Privacy in genetics research. Science 285:1359–1361
Knoppers BM, Hirtle M, Lormeau S, et al (1998) Control of DNA samples and information. Genomics 50:385–401
Beskow LM, Burke W, Merz JF, et al (2001) Informed consent for population-based research involving genetics. JAMA 286:2315–2321
March R, Cheeseman K, Doherty M (2001) Pharmacogenetics-legal, ethical and regulatory considerations. Pharmacogenomics 2:317–327
Weijer C, Emanuel EJ (2000) Ethics: protecting communities in biomedical research. Science 289:1142–1144
Wong M-L, Licinio J (2001) Research and treatment approaches to depression. Nat Rev Neurosci 2:343–351
National Bioethics Advisory Commission (1999) Research involving persons with mental disorders that may affect decision making capacity. National Bioethics Advisory Commission, Rockville
Roberts LW, Roberts B (1999) Psychiatric research ethics: an overview of evolving guidelines and current ethical dilemmas in the study of mental illness. Biol Psychiatry 46:1025–1038
Hall LL (1999) Medication discontinuation and symptom provocation in research: a consumer and family perspective. Biol Psychiatry 46:1017–1020
Carpenter WT, Schooler NR, Kane JM (1997) The rationale and ethics of medication-free research in schizophrenia. Arch Gen Psychiatry 54:401–407
Arboleda-Florez J, Weisstub DN (1997) Ethical research with the mentally disordered. Can J Psychiatry 42:485–491
Parker LS (2002) Ethical issues in bipolar disorders pedigree research: privacy concerns, informed consent, and grounds for waiver. Bipolar Disord 4:1–16
Foster MW, Sharp RR, Mulvihill JJ (2001) Pharmacogenetics, race, and ethnicity: social identities and individualized medical care. Ther Drug Monit 23:232–238
Epps PG, Rothstein MA (2002) Pharmacogenomics: ensuring equity regarding drugs based on genetic difference. In: Licinio J, Wong M-L (eds) Pharmacogenomics: the search for individualized therapies. Wiley-VCH, Los Angeles, pp 515–523
Exner DV, Dries DL, Domanski MJ, et al (2001) Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. N Engl J Med 344:1351–1357
Anonymous (2001) Genes, drugs and race. Nat Genet 29:239–240
Wilson JF, Weale ME, Smith AC, et al (2001) Population genetic structure of variable drug response. Nat Genet 29:265–269
Shah J (2003) Economic and regulatory considerations in pharmacogenomics for drug licensing and healthcare. Nat Biotechnol 21:747–753
Freund CL, Wilfond BS (2002) Emerging ethical issues in pharmacogenomics: from research to clinical practice. Am J Pharmacogenomics 2:273–281
Turecki G (2001) Suicidal behavior: is there a genetic predisposition? Bipolar Disord 3:335–349
Lesch KP, Merschdorf U (2000) Impulsivity, aggression, and serotonin: a molecular psychobiological perspective. Behav Sci Law 18:581–604
Danzon P, Towse A (2002) The economics of gene therapy and of pharmacogenetics. Value Health 5:5–13
Veenstra DL, Higashi MK, Phillips KA (2000) Assessing the cost-effectiveness of pharmacogenomics. AAPS Pharm Sci 2:E29
Steimer W, Potter JM (2002) Pharmacogenetic screening and therapeutic drugs. Clin Chim Acta 315:137–155
Milne CP (2002) Orphan products pain relief for clinical development headaches. Nat Biotechnol 20:780–784
Department of Health and Aged Care (2001) The orphan drug program and improving community access to effective drugs for rare diseases. Department of Health and Aged Care, Canberra
Rai AK (2002) Pharmacogenetic interventions, orphan drugs, and distributive justice: the role of cost-benefit analysis. Soc Philos Policy 19:246–270
Wong M-L, Alvarado I, Licinio J (2002) Pharmacogenomics of major depression and antidepressant treatment. In: Licinio J, Wong M-L (eds) Pharmacogenomics: the search for individualized therapies. Wiley-VCH, Los Angeles, pp 379–395
Brock TP, Valgus JM, Smith SR, et al (2003) Pharmacogenomics: implications and considerations for pharmacists. Pharmacogenomics 4:321–330
Gurwitz D, Weizman A, Rehavi M (2003) Education: teaching pharmacogenomics to prepare future physicians and researchers for personalized medicine. Trends Pharmacol Sci 24:122–125
Varmus H (2002) Getting ready for gene-based medicine. N Engl J Med 347:1526–1527
Alcalde MG, Rothstein MA (2002) Pharmacogenomics: ethical concerns for research and pharmacy practice. Am J Health Syst Pharm 59:2239–2240
Greendale K, Pyeritz RE (2001) Empowering primary care health professionals in medical genetics: how soon? how fast? how far? Am J Med Genet 106:223–232
Burgess MM (2001) Beyond consent: ethical and social issues in genetic testing. Nat Rev Genet 2:147–151
Acknowledgements
The authors would like to thank Sarah Yeates for her valuable assistance in the researching of this paper, and Lucy Carter for her helpful discussions and input. This work was funded in part by a grant from beyondblue: The National Depression Initiative.
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Morley, K.I., Hall, W.D. Using pharmacogenetics and pharmacogenomics in the treatment of psychiatric disorders: some ethical and economic considerations. J Mol Med 82, 21–30 (2004). https://doi.org/10.1007/s00109-003-0496-x
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DOI: https://doi.org/10.1007/s00109-003-0496-x