OPTIMUM: Optimizing Depression Treatment in Older Adults

The OPTIMUM Study is no longer recruiting participants. If you would like to be contacted about future projects, click here.


One half or more of older adults fail to get relief from depression with antidepressant pharmacotherapy. Treatment-resistant depression (TRD) in older adults is highly deleterious, because persistence of depression is a leading cause of disability, suicide, dementia, and premature mortality. Making it worse is the lack of evidence-supported treatments at a stage in life when medications’ benefit vs. risk ratio crucial. This study aims to provide the evidence that older adults need to get effective treatment that works best for them, improving their quality of life while minimizing risks of medications.

The study aims to close the evidence gap on late-life depression in three ways:

1. We will examine the comparative benefits and risks of antidepressant strategies (augmentation and switching) in older adults with TRD. We will focus on the effects on the outcomes that matter most to older adults, like well-being, adverse events, and falls.

2. We will explore how aging changes the balance of benefits vs. risks. With aging comes a decline in brain and systemic health that may alter the benefit/risk ratio of antidepressant strategies.

3. We will maximize stakeholder engagement to ensure relevancy to providers and patients alike. Armed with the knowledge of differential benefits and risks, stakeholders could provide personalized precision care that maximizes the benefits of TRD treatment strategies for older adults with minimizing risks.


The OPTIMUM Study is the largest study of Late-Life TRD to date. Participants will be 1500 older adults aged 60+ with current major depression that has failed to respond to 2+ adequate antidepressant trials. We will recruit across five sites: St. Louis and rural Missouri; Los Angeles City and County; Western Pennsylvania; New York City; and Toronto and rural Ontario.

Participants will be randomized to 10 weeks of one of three Step 1 strategies: aripiprazole augmentation, bupropion augmentation, or switch to bupropion. Those who do not attain remission in Step 1 will be randomized to 10 weeks of one of two Step 2 strategies: lithium augmentation or switch to nortriptyline. Those who complete acute treatment will be followed in a one-year continuation. This pragmatic RCT will be carried out in real-world clinical settings. Primary care and mental health clinical partners will provide treatments, with decision support from the study team. 

OPTIMUM is a five-site study (Washington University, Columbia University, University of Pittsburgh, University of Toronto, and University of California, Los Angeles) funded by the Patient-Centered Outcomes Research Institute. OPTIMUM is recruiting 1,500 community-living men and women aged 60 and older with treatment-resistant depression, defined as major depression that persists despite two or more prior antidepressant trials of adequate dose and duration. Individuals with normal cognition as well as MCI are included.

Outcomes: Psychological well-being is the patient-centered effectiveness outcome and remission from depression is the clinician-focused effectiveness outcome. Secondary patient-reported outcomes include physical function and social participation. Safety will be monitored through serious adverse events as well as falls and fall-related injuries. As well, the study will test how aging influences the relative benefits and risks of antidepressants for TRD.  Additionally, a qualitative study of patient and clinician partners will provide the lived experience of TRD and antidepressant strategies.


OPTIMUM Publications:

Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM): Study Design and Treatment Characteristics of the First 396 Participants Randomized

OPTIMUM is funded by a grant from the Patient-Centered Outcomes Research Institute. Click here to see the OPTIMUM study on the PCORI site