Consumer Warning for Genetic Tests Claiming to Predict Response to Medications: Implications for Psychiatry

To the Editor: On Nov. 1, 2018, the Food and Drug Administration (FDA) released a consumer warning about genetic tests that claim to predict patients’ responses to specific medications (https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624794.htm). The warning applies to pharmacogenomic tests used in all fields of medicine but holds particular importance for psychiatry given the increasing use of commercially marketed pharmacogenomic tests. Although manufacturers market pharmacogenomic tests to clinicians as being able to predict (and thus improve) antidepressant outcomes, the currently available evidence does not support such claims (1), as further articulated by the FDA statement that:

the relationship between DNA variations and the effectiveness of antidepressant medications has never been established. Moreover, … changes to patients’ medication based on genetic test results that claim to provide information on the personalized dosage or treatment regimens for some antidepressant medications … could potentially lead to patient harm.

The FDA released this warning 1 day after approving the first direct-to-consumer autosomal DNA test (23andMe Personal Genome Service Pharmacogenetic Reports; https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624753.htm). Although 23andMe makes no claim to inform pharmacotherapy outcomes, it reports allelic variants of genes relevant to pharmacokinetics and pharmacodynamics. The purpose of this FDA approval with simultaneous FDA warning might appear paradoxical, with the FDA approving the validity of the genetic test procedures while not approving the clinical use of such tests to guide treatment (e.g., the tests can identify genetic variants, but identifying the variants has no established generalizable clinical utility).

The FDA’s pharmacogenomic test warning, temporally juxtaposed with its approval of an at-home consumer genomics test, merits recognition about potential test misuse. We previously expressed concern that proprietary commercial pharmacogenomic tests lack sufficient evidence to support widespread clinical use (2–4). Existing manufacturer-sponsored pharmacogenomic clinical trials are not sufficiently powered to detect associations at levels of significance found in genome-wide association studies, are unreplicated, and suffer from design limitations that fail to demonstrate better outcomes than those achieved by psychopharmacologically knowledgeable practitioners (3–5).

The FDA statement is aligned with the conclusion drawn in a pharmacogenomic comprehensive review, published in the September 2018 issue of the Journal, which reported that “there are insufficient data to support the widespread use of combinatorial pharmacogenetic testing in clinical practice” (6). Accordingly, the FDA’s consumer warning is timely and of great importance, clearly communicating to providers and the public the state of the evidence. Further, in a time where clinicians and consumers are hopeful that pharmacogenetics could guide personalized medicine in psychiatry as decisively as in oncology, we must still be skeptical of hyperbolic research findings that promote false hope with unproven treatment approaches. In addition, the FDA statement may provide clinicians with clear, authoritative, evidence-based guidance to share with patients who request pharmacogenomic testing, as such requests become increasingly common given the energetic marketing efforts of pharmacogenomic companies.