The accrual and analysis of genomic sequencing data have identified specific genetic variants that are associated with major depressive disorder. Moreover, substantial investigations have been devoted to identifying gene-drug interactions that affect the response to antidepressant medications by modulating their pharmacokinetic or pharmacodynamic properties. Despite these advances, individual responses to antidepressants, as well as the unpredictability of adverse side effects, leave clinicians with an imprecise prescribing strategy that often relies on trial and error. These limitations have spawned several combinatorial pharmacogenetic testing products that are marketed to physicians. Typically, combinatorial pharmacogenetic decision support tools use algorithms to integrate multiple genetic variants and assemble the results into an easily interpretable report to guide prescribing of antidepressants and other psychotropic medications. The authors review the evidence base for several combinatorial pharmacogenetic decision support tools whose potential utility has been evaluated in clinical settings. They find that, at present, there are insufficient data to support the widespread use of combinatorial pharmacogenetic testing in clinical practice, although there are clinical situations in which the technology may be informative, particularly in predicting side effects.
Bibliographical noteFunding Information:
Dr. Carpenter has served as a consultant for Magstim, and she has received research grants and equipment for clinical trials (through a contract with Butler Hospital) from Cervel, Janssen, Neosync, and Neuronetics. Dr. Kalin has received research support from NIMH (grants R01 MH046729, P50MH100031, R01 MH081884, R01MH107563); he has served as a consultant for Actify Neurotherapies, CME Outfitters, the Pritzker Neuropsychiatric Disorders Research Consortium, and the Skyland Trail Advisory Board; and he serves as coeditor of Psychoneuroendocrinolgy (Elsevier). Dr. Rodriguez has received research support from NIMH (grant R01MH105461), the Brain and Behavior Research Foundation, and the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program, and she has served as a consultant for Allergan, BlackThorn Therapeutics, and Rugen Therapeutics. Dr. McDonald has received research support from Cervel Neurotherapeutics, the National Institute of Neurological Disease and Stroke (NINDS), NeoSync, Neuronetics, NIMH, the Patient-Centered Outcomes Research Institute, Soterix, and the Stanley Foundation; he has served as a consultant on the Neurological Devices Panel of the Medical Devices Advisory Committee, Center for Devices and Radiological Health, U.S. Food and Drug Administration,andheisanadhocmemberofseveralNIMHandNINDSstudy sections; he has served as a speaker for the Telecare Corporation; he receives royalties from Oxford University Press and is a section editor for Current Psychiatry Reports; he receives stipends as the Director of Review Course for the American Association of Geriatric Psychiatry and as section editor for Current Psychiatry Reports; he is also on the editorial boards of the American Journal of Geriatric Psychiatry and the Journal of ECT. Dr. Widge has received research support from the Brain and Behavior Research Foundation, Harvard University, NIH, and the U.S. Department of Defense; he has received device donations from Medtronic; he has served as a consultant for Medtronic; and he has multiple patent applications pending in psychiatric diagnostics and novel brain stimulation methods. Dr. Nemeroff has received research support from NIH and the Stanley Medical Research Institute; he has served as a consultant for Bracket (Clintara), Fortress Biotech, Intra-Cellular Therapies, Janssen Research and Development, Magstim, Navitor Pharmaceuticals, Prismic Pharmaceuticals, Sumitomo Dainippon Pharma, Sunovion Pharmaceuticals, TC MSO, Taisho Pharmaceutical, Takeda, and Xhale; he is a stockholder in AbbVie, Antares, BioGen Holdings, Celgene, Corcept Therapeutics Pharmaceuticals, OPKO Health, Seattle Genetics, and Xhale; he has served on scientific advisory boards for the American Foundation for Suicide Prevention, the Anxiety Disorders Association of America, Bracket (Clintara), the Brain and Behavior Research Foundation, the Laureate Institute for Brain Research, Skyland Trail, and Xhale; he has served on boards of directors for the American Foundation for Suicide Prevention, the Anxiety Disorders Association of America, and Gratitude America; income sources or equity of $10,000 or more include American Psychiatric Publishing, Bracket (Clintara), CME Outfitters, Takeda, and Xhale; and he holds patents on a method and devices for transdermal delivery of lithium (US 6,375,990B1) and a method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7,148,027B2). Dr. Zeier reports no financial relationships with commercial interests.