Biotype-assigned augmentation approach in resistant late life depression (baard)

This federal Cooperative Agreement award from the National Institute of Mental Health (NIMH) under the Mental Health Research Grants program (CFDA 93.242) provides $1,370,657 to The Washington University to develop and validate a clinical decision support tool called the Biotype-Assigned Augmentation Approach in Resistant Late-Life Depression (BAARD).

The key objectives are to leverage existing data from ~700 older adults with treatment-resistant late-life depression (TRLLD) to: 1) develop and validate a prototype BAARD tool for predicting remission based on patient biotypes, and 2) conduct a prospective randomized controlled trial (RCT) to evaluate the BAARD tool's effectiveness in guiding treatment selection for TRLLD compared to standard care. The project involves sub-awards to the Centre for Addiction and Mental Health and the University of Pittsburgh to support the biomarker development and RCT components. The award period is from Sep 2024 to Sep 2026.

Abstract

Up to half of depressed older adults do not respond to an initial antidepressant, and fewer than 20% achieve remission. Using a robust multi-site clinical trial network, we have completed two landmark randomized controlled trials (rcts) showing that augmentation of current antidepressant with aripiprazole (ARI) or bupropion (BUP) results in a 29% remission rate in trlld. In response to RFA-MH-24-120, we will use this and other existing clinical trial data to design and evaluate a clinical decision support tool, the biotype-assigned augmentation approach in resistant late-life depression (baard), to improve treatment selection using precision biomedical information. With integrated expertise in geroscience, psychopharmacology, cognition, molecular subtyping, neuroimaging, computational psychiatry, and qualitative research methods represented on our research team, we will use existing demographic, clinical, cognitive, genetic, proteomic, and high quality neuroimaging on ~700 participants to develop and test the baard tool. UG3 phase specific aims: design and validate the baard decision support tool. Aim 1, YR 1: develop the baard tool for treatment selection in trlld using data from two large multi-center trials ('IRL-grey' & 'optimum') and the embedded biomarker study ('OPT-neuro') (total n~700). Aim 2, YR 2: refine the baard biotype profile & analytic approach using data from individuals diagnosed with major depressive disorder (MDD) or treatment resistant depression (TRD) from the canadian biomarker integration network in depression (canbind, n~200) and UK biobank (UKB, n~2,400) studies, respectively. Go-no-go threshold for YRS 1-2: to proceed to the proposed UH3 RCT phase (n=300), our baard tool must achieve a combined predicted remission rate of ≥46% in cross-validation. This corresponds to a balanced accuracy of ≥75% for remission prediction in test data and will be assessed at the end of YR 1 and YR 2. UH3 phase specific aims: test the baard decision support tool in a prospective RCT. Aim 3, YRS 3-5: in the UH3 phase, we will randomize 300 adults aged ≥60 YRS with trlld (2:1) to baard tool- assigned treatment VS. Randomized treatment assignment (1:1 ARI:BUP) and compare remission rates based on the montgomery asberg rating scale score (madrs score