Just as others have become concerned about the use of nonvalidated pharmacogenetic (or genetic) tests in psychiatry, I too share that concern.1-5 If you do not like academic psychiatrists (“Ivory Tower” types), my second confession will seem like a confession. I started promoting pharmacogenetic tests in the 1990s—before they were fashionable—and now I am embarrassed after going through the 3 phases of pharmacogenetic testing (fear, failure, and hype).5
Early in the 1990s, a couple of pharmacologists opened my eyes to cytochrome P450 (CYP), which is involved in clozapine metabolism. Then a patient taught me that a CYP-mediated drug-drug interaction between caffeine and clozapine was important.6 Thus, after 20 years of studying pharmacology and treating many complex patients, I reached the conclusion that drug-drug interactions are frequently important and that pharmacogenetic tests are occasionally indicated in psychiatry.
In the early 2000s (the fear phase), pharmaceutical companies were scared of pharmacogenetic tests. In the later 2000s (the failure phase), I figured out that I was not going to become famous, since the early pharmacogenetic tests failed. In the current hype phase, I am embarrassed that nonvalidated pharmacogenetic tests are aggressively promoted by some companies.
The onset of the year of embarrassment
In January 2015, I was scheduled to lecture my department residents on psychopharmacology when one of them asked my opinion about a pharmacogenetic test that tells which drugs are good or bad for each patient. Another senior psychiatry resident had started ordering the test and was encouraging other residents to do so. My pharmacological arguments about the limitations of that test did not impress the resident. Who can blame him?
A company gave him a free test (saving him at least $2000) that told him in simple terms which psychiatric medication to use in each patient. Yet a professor lectured him about the need to study pharmacology and told him the following regarding selection of psychiatric drugs:
1 Using science to select the right drug for a patient is beyond our current scientific knowledge;
2 Once you choose a drug, selecting the right dosage may be relatively easy for some drugs; however,
3 Drug dosing is influenced not only by genetics, but also by environmental and personal factors.
The year of embarrassment continues
This experience of failure to convince my psychiatry residents of the appropriate use of pharmacogenetics tests led me to design a PowerPoint presentation to teach residents which pharmacogenetic tests are indicated and the complexity involved in interpreting them.7 Pharmacogenetic tests in the clinical environment should be limited to:
1 HLA-B*15:02 testing before starting carbamazepine in patients with Asian ancestry
2 CYP2D6 and/or CYP2C19 genotyping under the following conditions: always before prescribing tricyclic antidepressants, preferably combined with blood levels; and occasionally when seeing lack of effectiveness or adverse drug reactions with SSRIs, venlafaxine, pimozide, atypical antipsychotics dependent on CYP2D6 for their metabolism (aripiprazole, brexpiprazole, iloperidone, and risperidone), clozapine, or atomoxetine
On the other hand, genetic testing is not needed for CYP1A2, CYP2B6, CYP3A4, or CYP3A; brain neurotransmitters and/or transporter genes; and diagnosis of schizophrenia, depression, or bipolar disorder.
Dr. de Leon is Professor of Psychiatry at the University of Kentucky College of Medicine in Lexington, KY. He reports no conflicts of interest concerning the subject matter of this article.
1. Klitzman R. The need for vigilance in the marketing of genomic tests in psychiatry. J Nerv Ment Dis. 2015;203:809-810.
2. Howland RH. Pharmacogenetic testing in psychiatry: not (quite) ready for primetime. J Psychosoc Nurs Ment Health Serv. 2014;52:13-16.
3. Dubovsky SL. The limitations of genetic testing in psychiatry. Psychother Psychosom. 2016;85:129-135.
4. Preskorn SH. Genetic and related laboratory tests in psychiatry: what mental health practitioners need to know. Curr Psychiatry. 2016;15:19-22, 58.
5. de Leon J. Pharmacogenetic tests in psychiatry: from fear to failure to hype (editorial). J Clin Psychopharmacol. 2016;36:299-304.
6. Odom-White A, de Leon J. Clozapine levels and caffeine. J Clin Psychiatry. 1996;57:175-176.
7. de Leon J. Pharmacogenetic testing in psychiatry. 2016. http://inhn.org/fileadmin/Programs/DE_Leon_Pharmcgenetic_testing.pdf. Accessed September 20, 2016.
8. The Secretary’s Advisory Committee on Genetics, Health and Society (SACGHS). Coverage and Reimbursement of Genetic Tests and Services, 2006. http://osp.od.nih.gov/office-clinical-research-and-bioethics-policy/genetics-health-and-society/sacghs-archives/documents. Accessed August 4, 2016.