Precision Medicine or Pretending? Depressing News for Genomic Testing

EBM Focus - Volume 17, Issue 27

Reference: JAMA. 2022 Jul 12;328(2):151-161

Precision medicine sounds cool. But precisely what are we doing with it? Outside of cancer treatment and certain genetic conditions, there is little evidence of clinical benefit for using genomic testing to guide medical care or medication selection. Thanks to advertising and social media algorithms, however, it’s not uncommon for patients to ask for genetic testing to help pick “the right” antidepressant medication for them. But does this actually help? The theory is that knowing how an individual will metabolize specific antidepressants will lead to better treatment outcomes through more precise medication selection or titration.

The PRIME trial enrolled nearly 2000 people (75% male) with major depressive disorder getting care through the Veterans Administration. Investigators used the PHQ9 and other validated questionnaires to measure treatment success over a 24-week period. In this unblinded pragmatic trial, providers were allowed to prescribe antidepressants as they typically would, but they had access to genomic test results for patients randomized to the genomic testing group. The study results as reported are a little confusing. They demonstrate a modest but significant difference in remission rates between groups over 24 weeks, but not at 24 weeks. What does that even mean? We think it likely reflects nonsignificant improvements seen at several time points along the way. But even the “modest, nonpersistent effect on remission rates” that the authors report is suspect, given that it’s an unblinded study at high risk of placebo effect, there were several important protocol amendments including a change to the primary outcome, and the amended primary outcome reads more like a composite.

So will genomic testing impact prescribing of antidepressants? Probably. Should it? Probably not. Perhaps this is precisely what is wrong with a ‘more is better’ approach to information acquisition in this day and age.

Clinical Take-Home Point: Don’t waste time and money on genomic testing to direct antidepressant prescribing.

EBM Pearl: Protocol amendments are red flags. Trust your gut if you feel confused by study methods or the reporting of results. It’s worth the effort to take a closer look.

DynaMed EBM Focus Editorial Team

This EBM Focus was written by Katharine DeGeorge, MD, MS, Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Dan Randall, MD, Deputy Editor at DynaMed; Carina Brown, MD, Assistant Professor at Cone Health Family Medicine Residency; Nicole Jensen, MD, Family Physician at WholeHealth Medical; Vincent Lemaitre, PhD, Senior Medical Writer at DynaMed; and Sarah Hill, MSc, Associate Editor at DynaMed.