REVIEW OF: Perlis RH et al, Depress Anxiety 2020;37(9):834–841

STUDY TYPE: Randomized controlled trial

By tailoring medications to a patient’s genetic profile, pharmacogenomics promises less medication trial and error, fewer side effects, and better overall outcomes. But does knowing a patient’s pharmacogenetic profile really improve treatment for some of the most common illnesses that we see, like depression? So far the controlled trials have been largely negative, but they’ve mainly focused on the Genesight panel. This trial tested the Genecept panel, which includes most of the genes in the Genesight panel but adds a few pharmacodynamic elements that have only preliminary evidence for use (eg, BDNF, melanocortin, and major histocompatibility complex).

This randomized controlled trial enrolled 314 adults with moderate to severe major depressive disorder who had already failed 1–3 antidepressant medications in the current depressive episode. Half the patients received treatment that was actively guided by the test, while the other half received treatment as usual. The primary outcome, change in Hamilton Depression Rating Scale score, was measured over eight weeks of treatment. The patients and researchers performing the rating scales were blinded to the treatment arm assignment, but the treating provider was not blinded.

At the end of the trial, the changes in depression scores (p = 0.53), rates of response (p = 0.17), and rates of remission (p = 0.23) were all no different between the two groups. Most of the secondary outcomes also showed no difference between the groups, including a self-report rating scale, the Clinical Global Impression-Improvement scale, and patient rating of side effects.

The authors did find that patients were more likely to remit when their medications were concordant with their test results. This finding, however, was only positive on post-hoc analysis, which means it is prone to false positives and should be interpreted with caution.

TCPR’s Take
Genecept joins the list of companies that have failed to show any benefit associated with genetic testing, even in patients who did not respond to one or more antidepressants. While this does not support the routine use of genetic testing, it doesn’t mean the tests do nothing. Consistent with earlier studies, patients fared worse when their medications were misaligned with their genetic results, but those misalignments are likely too rare to make a measurable difference.