What the study found
The study found that biomarker-guided assignment to sertraline and bupropion, two antidepressants, did not produce significant overall differences when the assigned drug matched versus did not match a person's biomarkers. It did find better symptom reduction for some biomarker-defined groups, especially people with positive markers for both drugs or for either drug compared with people with two negative markers.
Why the authors say this matters
The authors conclude that this is the first study using biobehavioral markers to prospectively guide assignment to two widely used antidepressants. They say the findings provide foundations for larger personalized treatment studies of major depressive disorder.
What the researchers tested
The researchers developed algorithms from a multisite study to predict response to sertraline and bupropion in major depressive disorder. They then tested these markers in an independent, prospective clinical trial of unmedicated people with major depressive disorder using a biomarker-guided sequential multiple-assignment design, which is a study design that assigns treatments in stages based on earlier responses or markers.
What worked and what didn't
In the training sample, leave-one-out cross-validation models performed well, with area under the curve values from 0.66 to 0.86. In the preregistered clinical trial, no significant differences were seen for drug assignment consistent versus inconsistent with biomarkers, but symptom reduction trajectories differed for people with positive markers for both medications or either drug compared with those with two negative markers; the abstract reports a 66.8% boost in response rate.
What to keep in mind
The abstract does not describe detailed limitations beyond the mixed trial results and the need for larger personalized treatment studies. The findings are reported for unmedicated individuals with major depressive disorder in a single prospective trial, so the available summary does not state how broadly they apply.
Key points
- The trial tested biomarker-guided assignment to sertraline and bupropion for major depressive disorder.
- Overall, matching treatment to biomarkers did not significantly change outcomes.
- Some biomarker-defined groups showed better symptom reduction than the group with two negative markers.
- The training models showed area under the curve values from 0.66 to 0.86.
- The authors say this is the first prospective study using biobehavioral markers to guide these two antidepressants.
Disclosure
- Research title:
- Biomarker-guided antidepressant assignment showed mixed benefits
- Authors:
- Peter Zhukovsky, Manuel Kuhn, Lauren R. Borchers, Boyu Ren, Sarah E. Woronko, Mohan Li, Choi Sze Tracy Lam, Ethan M. Zhang, Kerry J. Ressler, Brian P. Brennan, Gordana Vitaliano, Diego A. Pizzagalli
- Institutions:
- Centre for Addiction and Mental Health, Charité – Universitätsmedizin Berlin, Freie Universität Berlin, Harvard University, Harvard University, Harvard University, Harvard University, Harvard University, Harvard University, Harvard University, Harvard University, Humboldt-Universität zu Berlin, McLean Hospital, McLean Hospital, McLean Hospital, McLean Hospital, McLean Hospital, McLean Hospital, McLean Hospital, McLean Hospital, McLean Hospital, McLean Hospital, McLean Hospital, McLean Hospital, University of California, Irvine, University of Toronto
- Publication date:
- 2026-07-06
- OpenAlex record:
- View
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