Augmenting Antidepressants With Aripiprazole Improves Symptoms in TRD

Augmenting an existing antidepressant regimen with aripiprazole is associated with more favorable outcomes compared with switching to bupropion among adults aged 60 years and older with treatment-resistant depression (TRD). These findings were published in The New England Journal of Medicine.

The Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM; ClinicalTrials.gov Identifier: NCT02960763) trial was an investigator-initiated, 2-step, open-label trial conducted at 5 sites in North America between 2017 and 2019. In step 1, patients (n=619) aged 60 years and older with TRD were randomly assigned in a 1:1:1 ratio to augment their current antidepressant regimen with aripiprazole (n=211) or bupropion (n=206) or switch to bupropion (n=202). Those who did not achieve remission at week 10 (n=125) or skipped step 1 (n=123) were randomly assigned in a 1:1 ratio to augment their regimen with lithium (n=127) or switch to nortriptyline (n=121) for 10 weeks.

The primary outcome of this study was achieving psychological well-being, defined as National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscores of 50 points or higher. Remission was defined as Montgomery-Åsberg Depression Rating Scale (MADRS) scores 10 points or lower.

The 5 study cohorts comprised patients with mean ages of 68.0 to 69.7 years, 68.2% to 70.9% were women, 82.0% to 91.3% were White, and they had mean ages of 29.0 to 34.5 years at major depressive disorder onset.

After 10 weeks of therapy, the greatest improvement from baseline in the psychological well-being outcome was observed among the aripiprazole augmentation group (mean difference [MD], 4.83 points), followed by the bupropion augmentation (MD, 4.33 points), lithium augmentation (MD, 3.17 points), nortriptyline switch (MD, 2.18 points), and bupropion switch (MD, 2.04 points) groups.

The greatest decrease in MADRS scores from baseline to 10 weeks was observed in the aripiprazole augmentation group (MD, -7.60 points), followed by the bupropion augmentation (MD, -7.23 points), nortriptyline switch (MD, -5.33 points), lithium augmentation (MD, -4.63 points), and bupropion switch (MD, -4.14 points) groups.

Compared with the bupropion switch group, both augmentation with aripiprazole (risk ratio [RR], 1.50; 95% CI, 1.06-2.13) and bupropion (RR, 1.49; 95% CI, 1.04-2.12) were associated with a greater likelihood of remission. Augmentation with lithium was not associated with a greater likelihood of remission compared with switch to nortriptyline (RR, 0.84; 95% CI, 0.53-1.36).

Findings from the post hoc sensitivity analysis were generally consistent with the primary results.

The per-patient rates of serious adverse events were highest for the bupropion switch group (mean, 0.12) and lowest for the aripiprazole augmentation group (mean, 0.07). The number of injurious falls per group ranged between 52 (bupropion augmentation) to 16 (nortriptyline switch).

The most common adverse events included dizziness or impaired balance, gastrointestinal distress, reduced salivation, tension or anxiety, and reduced or disturbed sleep.

The major limitation of this study was the lack of a nonactive comparator group.

“This pragmatic trial involving older persons with treatment-resistant depression showed greater improvement in psychological well-being and a numerically higher incidence of remission with aripiprazole augmentation than with a switch to bupropion,” the study authors wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.