Aripiprazole Augmentation Improves Remission Rates for Treatment Resistant Depression

Published on: 

The results show 28.9% of the aripiprazole augmentation group achieved remission, compared to 28.2% of the bupropion augmentation group and 19.3% of the bupropion switch group.

A new analysis show augmenting to aripiprazole results in higher levels of remission for older adults with treatment resistant depression (TRD) compared to augmenting or switching to bupropion.1

A team, led by Eric J. Lenze, MD, Washington University School of Medicine in St. Louis, compared several treatment options for patients aged at least 60 years with treatment resistant depression.

In the past, research has seldomly focused on the benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression.

In the two-step, open-label trial, the investigators examined adult patients aged 60 years or older with TRD. To begin the trial, each participant was assigned to either augmentation of existing antidepressant medication with aripiprazole (n = 211), augmentation with bupropion (n = 206), or a switch from existing antidepressant medication to bupropion (n = 202). Participants who did not benefit from or were ineligible for step 1 were assigned to either augmentation with lithium (n = 127) or a switch to nortriptyline (n = 121) in step 2.

Both steps lasted approximately 10 weeks

Step One

The investigators sought primary outcomes of the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales.

They also sought secondary outcomes of the remission of depression.

The results show well-being scores increased by 4.83 points in the aripiprazole augmentation group, compared to 4.33 points for the bupropion augmentation group and 2.04 points for the bupropion switch group.

The difference between the aripiprazole augmentation group and the switch group was 2.79 points (95% confidence interval [CI], 0.56-5.02; P = 0.014, with a prespecified threshold P value of 0.017). However, the between-group differences were not significant for either aripiprazole augmentation compared to bupropion augmentation or for bupropion augmentation compared to a switch to bupropion.

Looking at remission rates, 28.9% of the aripiprazole augmentation group achieved remission, compared to 28.2% of the bupropion augmentation group and 19.3% of the bupropion switch group.

In addition, the rate of falls were highest in the bupropion augmentation cohort.

Step Two

The step 2 results show well-being scores improved by 3.17 points in the lithium group, compared to 2.18 points in the nortriptyline group (difference, 0.99; 95% CI, -1.92 to 3.91), while remission occurred in 18.9% of the first group and 21.5% in the second group. The falling rates were similar between the 2 groups.

“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,” the authors wrote. “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.”

Additional Comment

In an accompanying editorial. Gemma Lewis, PhD, and Glyn Lewis, PhD, analyzed the results.2

The pair noted the safety differences in the treatment, showing aripiprazole was associated with a lower rate of falls than bupropion augmentation, but the overall efficacy is not that impressive.

“These findings therefore supported aripiprazole augmentation as being a potentially better overall strategy for older persons who have not had a response to conventional antidepressants,” they said. “The percentage of patients who had remission in the aripiprazole-augmentation group was approximately 9 percentage points higher than in the switch-to-bupropion group. This modest benefit is worthwhile in this population, but overall outcomes were nevertheless still poor; only 29% of the patients in the augmentation groups had remission after treatment.”


Lenze, E. J., Mulsant, B. H., Roose, S. P., Lavretsky, H., Reynolds, C. F., Blumberger, D. M., Brown, P. J., Cristancho, P., Flint, A. J., Gebara, M. A., Gettinger, T. R., Lenard, E., Miller, J. P., Nicol, G. E., Oughli, H. A., Pham, V. T., Rollman, B. L., Yang, L., & Karp, J. F. (2023). Antidepressant augmentation versus switch in treatment-resistant geriatric depression. New England Journal of Medicine.

Lewis, G., & Lewis, G. (2023). Aripiprazole augmentation in older persons with treatment-resistant depression. New England Journal of Medicine.