April 11, 2023

Relieving treatment-resistant depression in older adults

At a Glance

  • For older adults whose depression persisted while taking an antidepressant, adding aripiprazole had greater benefits than switching to another antidepressant.
  • The findings add much-needed evidence to help guide treatment decisions for older adults with hard-to-treat depression.
Man chatting with his grandson while fishing. Depression can be difficult to treat, particularly in older adults. My Agency / Shutterstock

Depression is common among older adults, and treatment with standard antidepressants doesn’t always work. When a person’s depression persists after trying at least two different antidepressant drugs, it is called treatment-resistant depression. In these cases, physicians may add a second medication. Alternatively, they might suggest switching to a different class of antidepressant. But there’s only limited evidence from clinical trials about which approaches might be best.

To learn more, a research team led by Dr. Eric J. Lenze of the Washington University School of Medicine in St. Louis conducted a clinical trial to assess different approaches to treatment-resistant depression in older patients. The study enrolled 619 people, ages 60 and older. All had major depression that did not improve after trying at least two courses of a conventional antidepressant.

In the main stage of the study, 619 patients were randomly assigned to one of three groups. The first group continued to take their prescribed antidepressant and added the antipsychotic drug aripiprazole (Abilify), which is often used to treat major depression. The second also continued their prescribed antidepressant but added the antidepressant bupropion (Wellbutrin). The third group gradually tapered off their current antidepressant and switched to bupropion.

The primary outcome was psychological well-being, which was assessed via a survey tool called the NIH Toolbox Positive Affect and General Life Satisfaction survey. The results were published on March 23, 2023, in the New England Journal of Medicine.

After 10 weeks of receiving treatment, the group with added aripiprazole had significantly greater improvements in well-being than the group that switched to bupropion. The group with added bupropion showed similar improvements to those with added aripiprazole; however, these improvements were not large enough compared to switching to bupropion to prove the approach was more effective.

The groups with added aripiprazole or bupropion both had more easing of depression symptoms than the switched group. Depression was relieved in 29% of those with added aripiprazole and in 28% of those with added bupropion, compared to 19% in the switched group.

A safety analysis found that the risk of falling was slightly higher in the group with added bupropion than the group with added aripiprazole. More study is needed to test whether such risks could be lowered by adjusting medication doses.

A second stage of the study included 248 patients who were ineligible for the first stage or hadn’t improved after 10 weeks of treatment. They were randomly assigned to receive two older antidepressant strategies: additional treatment with lithium or a switch to nortriptyline. After 10 weeks, well-being scores and symptom relief in the two groups showed similar modest improvements. Depression was relieved in 19% of patients receiving lithium and in 22% of those who switched to nortriptyline.

“Because depression and anxiety in older adults may accelerate cognitive decline, there’s an urgency to find more effective treatment strategies,” Lenze says.

“We found that adding aripiprazole showed the greatest combination of benefits and safety, in terms of depression remission, improvements in psychological well-being—which means how positive and satisfied patients felt—and adverse events such as falls,” he adds. “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.”

—by Vicki Contie

Related Links

References: Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression. Lenze EJ, Mulsant BH, Roose SP, Lavretsky H, Reynolds CF 3rd, Blumberger DM, Brown PJ, Cristancho P, Flint AJ, Gebara MA, Gettinger TR, Lenard E, Miller JP, Nicol GE, Oughli HA, Pham VT, Rollman BL, Yang L, Karp JF. N Engl J Med. 2023 Mar 23;388(12):1067-1079. doi: 10.1056/NEJMoa2204462. Epub 2023 Mar 3. PMID: 36867173.

Funding: NIH’s National Center for Advancing Translational Sciences (NCATS), National Center for Complementary and Integrative Health (NCCIH), and National Institute of Mental Health (NIMH); Patient-Centered Outcomes Research Institute.