Clinical Study on Augmenting Medications for Treatment-Resistant Depression in Older Adults Shows Promise

March 3, 2023

The OPTIMUM study found that adding a medication, rather than switching medications, may help older adults with treatment-resistant depression.

The results of a clinical trial to find more effective treatment strategies for treatment-resistent depression in older adults were promising while highlighting the need for additional treatment options.

The results of a clinical trial to find more effective treatment strategies for treatment-resistent depression in older adults were promising while highlighting the need for additional treatment options.

A clinical trial including a researcher in the University of Arizona College of Medicine – Tucson’s Department of Psychiatry found that adding the medication aripiprazole to the antidepressant being taken by older patients with difficult-to-treat depression improved participant well-being and resulted in higher depression remission rates. The paper, “Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression,” was published today in the New England Journal of Medicine. 

portrait of jordan karp in a white doctor's coat

Jordan Karp, MD, is a professor and chair of the Department of Psychiatry in the College of Medicine – Tucson.

Overall, antidepressants are highly effective for the majority of people suffering from clinical depression. At least half of all people with depression feel much better after they begin taking the first medication they try, and almost half of the remainder not helped by a first drug improve when switched to a second drug. Still, that leaves a sizeable group with clinical depression that does not respond to two treatments.

“This study was designed to answer a continuing problem in our field,” said senior author Jordan F. Karp, MD, professor and chair of the Department of Psychiatry. “Any given treatment is likely to help only a subset of people, and ideally, we would like to know, in advance, who is most likely to be helped.”

Over two phases, the OPTIMUM study engaged 742 participants who were 60 years old and older and had depression which had not responded to at least two different antidepressant medications. In the first phase, 619 patients on antidepressants were divided into three groups. The first group stayed on their current antidepressant with aripiprazole (brand name Abilify) added to their medication regimen. The second group added bupropion (brand name Wellbutrin) along with their current antidepressant, and the third group tapered off of their antidepressant and were switched to bupropion.

At the end of the 10-week study, conducted by clinicians via phone or in-person visits, researchers found the best clinical and safety outcomes for the first group – the one with aripiprazole added to their current antidepressant medication. 

In the second phase, 248 participants received either lithium augmentation of their currently prescribed antidepressant or were switched to nortriptyline. The rate of alleviating depression in the second group was approximately 20% and there wasn’t a significant difference between augmenting with lithium or switching to nortriptyline. 

But even the best treatment strategy — adding aripiprazole to an antidepressant — was not markedly successful for many older patients with treatment-resistant depression.

“We found that adding aripiprazole led to higher rates of depression remission and greater improvements in psychological well-being – which means how positive and satisfied patients felt – and this is good news,” said the study’s contact principle investigator and first author Eric J. Lenze, MD, the Wallace and Lucille Renard Professor and head of the Department of Psychiatry at Washington University. “However, even that approach helped only about 30% of people in the study with treatment-resistant depression, underscoring the need to find and develop more effective treatments that can help more people.

“Often, unless a patient responds to the first treatment prescribed for depression, physicians follow a pattern in which they try one treatment after another until they land on an effective medication,” Dr. Lenze added. “It would be beneficial to have an evidence-based strategy we can rely on to help patients feel better as quickly as possible.”

The problem is particularly difficult in older adults, many of whom already are taking several medications for other conditions such as high blood pressure, cardiac issues or diabetes; switching to new antidepressants every few weeks or adding other psychiatric drugs can be complicated. In addition, because depression and anxiety in older adults may accelerate cognitive decline, there’s an urgency to find more effective treatment strategies, the researchers said.

“While the results of this pragmatic trial are promising and when implemented will improve the care of older adults with treatment-resistant depression, the fact that the majority of participants did not experience clinical benefit reveals the limitations of available effective treatments for this rapidly growing segment of our society,” Dr. Karp added.

The study was funded in part by the Patient-Centered Outcomes Research Institute (TRD-1511-33321), and the National Center for Advancing Translational Sciences and National Institute of Mental Health of the National Institutes of Health (5RO1 MH114980, K24 AT009198, R01 MH114981)


Jamie Manser
Department of Psychiatry