Genetic screening for SSRI drug response among those with major depression: great promise and unseen perils.
This article examines evidence for the potential benefit of genetic testing for SSRI response, as well as potential ethical and practical implications of the implementation of this test into standard psychiatric practice. We reviewed three areas of the literature: the burden of treatment-resistant and treatment-intolerant major depressive disorders, the evidence for the value of genetic testing to predict drug response, and the ethical and practical issues of genetic testing in usual care. Treatment resistance and treatment intolerance are common for persons treated with selective serotonin reuptake inhibitors (SSRIs) and are associated with both financial and quality-of-life costs. There is strong evidence from association studies that some polymorphisms are associated with SSRI response. However, no randomized trials have yet tested the efficacy of genetic tests to improve outcome in those with treatment resistance or treatment intolerance to SSRIs. Given the nonspecific nature of the test proposed, several ethical concerns are also involved with administering the genetic tests to patients. A randomized trial comparing response in those treated with standard psychiatric care and in those treated with psychiatric care tailored as a result of genetic test results should be completed before the implementation of these tests can be considered. Additionally, the ethical and practical questions concerning the tests must be addressed now, so that the potential impact of these tests on patient care can be well understood prior to adoption in standard practice.
Rasmussen-Torvik
Laura J
LJ
Division of Epidemiology and Community Health and Division of Health Services Research and Policy, School of Public Health, University of Minnesota, Minneapolis, MN 55454, USA. rasm0218@umn.edu
McAlpine
Donna D
DD
D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004252:DNA Mutational Analysis; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D004992:Ethics, Medical; D030661:Genetic Privacy / Q000941:ethics; D005820:Genetic Testing / Q000941:ethics*; D005838:Genotype; D006801:Humans; D010349:Patient Compliance; D010597:Pharmacogenetics / Q000941:ethics; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D018687:Antidepressive Agents, Second-Generation; D019389:Cytochrome P-450 CYP2D6; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human