Adjunctive antipsychotic treatment appears to help elderly with treatment-resistant depression

Among patients over 60 with treatment-resistant depression, adding the antipsychotic drug aripiprazole (Abilify) to their treatment appears to be a more effective strategy than switching antidepressants.

Researchers reported these findings on March 3, 2023 in the New England Journal of Medicine.

“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,” said author Eric J. Lenze, MD, principal investigator and head of the Department of Psychiatry at Washington University School of Medicine in St. Louis, Missouri. “It would be beneficial to have an evidence-based strategy we can rely on to help patients feel better as quickly as possible. 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. 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.”

As background, the authors noted that aripiprazole was approved by the U.S. Food and Drug Administration/FDA in 2002 to treat schizophrenia. It has become commonly used off-label as an add-on treatment for clinical depression in younger patients who do not respond to antidepressant monotherapy.

The researchers conducted a two-step, open-label trial enrolling adults 60 years of age or older with treatment-resistant depression.

In step 1, they randomized subjects to augmentation with aripiprazole of existing antidepressant medication, augmentation with bupropion or a switch from existing antidepressant medication to bupropion.

Subsequently, the subjects who did not benefit from or were ineligible for step 1 were randomized in step 2 to augmentation with lithium or a switch to nortriptyline.

Each step lasted 10 weeks.

The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (Higher scores indicate greater well-being).

In step 1, the investigators enrolled 619 subjects, assigning 211 to aripiprazole augmentation, 206 to bupropion augmentation and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively.

The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (P=0.014, with a prespecified threshold P value of 0.017).

In step 2, the investigators enrolled 248 subjects and assigned 127 to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively.

The authors concluded, “In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar.”