Antidepressant augmentation with aripiprazole improves well-being in treatment-resistant depression: NEJM

They said that there is a lack of data and evidence extensively explaining the benefits and risks of augmenting or switching antidepressants in older adults with a treatment-resistant depression history.

Researching further, we conducted a two-step, open-label trial: In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who had not benefitted from step 1 were assigned to step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline, they said.

The duration of each step was ten weeks, and the primary and secondary outcomes measured were changed from baseline in psychological well-being and remission of depression, respectively.

The study results could be summarised as follows:

• A total of 619 patients were enrolled.
• Two hundred eleven patients were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. In these, there was an improvement in well-being scores 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.
• There were no significant between-group differences for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion.
• In the aripiprazole-augmentation group, bupropion-augmentation group, and switch-to-bupropion group, 28.9 %, 28.2 %, and 19.3 % had remission.
• Bupropion augmentation had the highest rate of falls.

Step 2 results:

• 248 patients were enrolled
• One hundred twenty-seven in lithium augmentation and 121 to a switch to nortriptyline.
• There was an improvement in Well-being scores by 3.17 points and 2.18 points, respectively, with a difference of 0.99.
• 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group had remission.
• There were similar rates of falling in the two groups.

The Patient-Centered Outcomes Research Institute funded the study.

This two-part observational study found that antidepressant augmentation improved the well-being of older adults with treatment-resistant depression compared with medication switching.

Further investigation is warranted based on the findings of the study.

Further reading:

Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression. DOI: 10.1056/NEJMoa2204462