The BAARD Study : Evaluating a Computerized Approach to Treatment Selection in Older Adults With Treatment Resistant Depression. (BAARD)

Biotype-assigned Augmentation Approach in Resistant Late-Life Depression (BAARD): a Randomized Controlled Trial

The goal of this clinical trial is to test whether a personalized approach to treatment selection improves symptoms in older adults with treatment-resistant depression.

The main questions it aims to answer is:

Will using the BAARD predictive models to select medications lead to better depression outcomes, compared to randomly selecting medications?

Researchers will use the BAARD predictive models or random assignment to choose one of two medications to add to patients' current treatment. Patients will be asked to take either aripiprazole or bupropion along with their current medication.

Participants will:

Take Aripiprazole or Bupropion in addition to their current medication for 10 weeks.

Complete follow-up assessments every 1-2 weeks for checkups.

Study Overview

• Status: Not yet recruiting
• Conditions: Treatment Resistant Depression; Depression - Major Depressive Disorder; Late Life Treatment Resistant Depression
• Intervention / Treatment: Drug: Aripiprazole Augmentation; Drug: Bupropion Augmentation

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ginger E Nicol, MD; Phone Number: 314-747-1862; Email: nicolg@wustl.edu
• Study Contact Backup: Name: Teddi L Gray; Phone Number: 3147471862; Email: grayt@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 60 years and older

2. Diagnosis of treatment resistant depression, as verified by:

   1. Diagnosis of DSM-5 Major Depressive Disorder according to Structured Clinical Interview for DSM-5 Disorders (SCID) AND
   2. Baseline score of at least 10 on the 9-item Patient Health Questionnaire (PHQ-9) AND
   3. Either i. At least 2 prior antidepressant trials in the current episode of adequate dose and duration as determined with the Antidepressant Treatment History Form (ATHF), OR ii. one failed trial of a serotonin norepinephrine reuptake inhibitor (SNRI) of adequate dose and duration, including the current antidepressant, OR iii. failed at least 1 antidepressant trial of adequate dose and duration as determined with the ATHF in a prior episode and present in relapse while on another antidepressant of adequate dose and duration as determined with ATHF
3. Ability to provide informed consent and complete the study assessments Taking antidepressant at adequate dose for at least 4 weeks

Exclusion Criteria:

1. Dementia, as defined by Short Blessed Test score at least10 and/or documented diagnosis of dementia.
2. Lifetime diagnosis of DSM 5 Bipolar I or II Disorder, Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, Delusional Disorder, or current psychotic symptoms, or current (within 3 months) moderate to severe alcohol or substance use disorder as diagnosed by the SCID.
3. High risk for suicide, defined as a 4 or 5 on C-SSRS46 (indicating active suicidal ideation with current or recent intent or plan), and unable to be managed safely in the clinical trial. Urgent psychiatric referral will be made in these cases.
4. Contraindication to study medications (aripiprazole or bupropion XL), as determined by study physician, including history of intolerance or non-response to bupropion (or equivalent bupropion containing drug) as an augmentation agent at greater than or equal to 300 mg or aripiprazole as an augmentation agent at greater than or equal to 5 mg.
5. Physical conditions that, in the estimation of the study physician, prevent safe participation or suggest a high probability of death, or unstable medical illnesses that are not under medical management.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAARD-assigned; The BAARD predictive model will use individual participants' data to advise which of two treatments to select, aripiprazole or bupropion.	Drug: Aripiprazole Augmentation; Aripiprazole augmentation will be started at 2 mg and increased based on symptoms and tolerability up to a maximum dose of 15 mg.; Other Names: Aripiprazole; Drug: Bupropion Augmentation; Bupropion augmentation will be started at 150 mg and increased based on symptoms and tolerability up to a maximum dose of 450 mg.; Other Names: Bupropion
Active Comparator: Randomly assigned; The randomly assigned arm will randomly assign one of two treatments to select, aripiprazole or bupropion.	Drug: Aripiprazole Augmentation; Aripiprazole augmentation will be started at 2 mg and increased based on symptoms and tolerability up to a maximum dose of 15 mg.; Other Names: Aripiprazole; Drug: Bupropion Augmentation; Bupropion augmentation will be started at 150 mg and increased based on symptoms and tolerability up to a maximum dose of 450 mg.; Other Names: Bupropion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission from Depression as measured by Montgomery-Asberg Depression Rating Scale (MADRS) score ≤10	The MADRS is a 10-item instrument used to assess depression severity. In this trial the MADRS will be used to assess remission of depression, defined as a MADRS score ≤10. The total MADRS score ranges from 0-60, with higher scores indicating increased severity of depression.	Week 10

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Ginger E Nicol, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): March 15, 2029
• Study Completion (Estimated): September 15, 2029

Study Registration Dates

• First Submitted: September 3, 2026
• First Submitted That Met QC Criteria: September 3, 2026
• First Posted (Actual): September 9, 2026

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinolones; Quinolines; Ketones; Piperazines; Propiophenones; Aripiprazole; Bupropion
• Other Study ID Numbers: 202603103; 1UG3MH137353-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No