Antidepressant Augmentation Improves Well-Being in Older Adults with Treatment-Resistant Depression: NEJM

USA: New research published in the New England Journal of Medicine has shed light on the benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression.

There has been limited research conducted on the advantages and drawbacks of augmenting or switching antidepressants in older adults who are experiencing treatment-resistant depression.

The two-step, open-label trial involved 619 patients aged 60 years or older who had treatment-resistant depression. In step 1, patients were randomly assigned to receive a 1:1:1 ratio augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion.

Patients who did not benefit from or were ineligible for step 1 were then randomly assigned in step 2 to a 1:1 ratio augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks.

The primary outcome of the study was the change from baseline psychological well-being, assessed using the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales.

The study revealed the following clinical findings:

1. In Step 1, Well-being scores improved by 4.83 points in the aripiprazole-augmentation group, 4.33 points in the bupropion-augmentation group, and 2.04 points in the switch-to-bupropion group.
2. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points, which was statistically significant.
3. The study also found that remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group.
4. In Step 2, well-being scores improved by 3.17 points in the lithium-augmentation group and 2.18 points in the switch-to-nortriptyline group.
5. Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group. The rates of falling were similar in the two groups.

The study's lead author, Dr. Eric J Lenze, emphasized the importance of considering the risks and benefits of different treatment options for older adults with treatment-resistant depression. He noted that while aripiprazole augmentation was associated with a higher incidence of remission and greater improvement in well-being, it also carried the risk of weight gain and metabolic abnormalities.

Dr. Lenze concluded that "Older adults with treatment-resistant depression require careful evaluation and individualized treatment planning that considers the risks and benefits of each intervention. The study highlights the need for further research to optimize treatment approaches in this population.”

Reference:

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. Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression. N Engl J Med. 2023 Mar 23;388(12):1067-1079. doi: 10.1056/NEJMoa2204462. Epub 2023 Mar 3. PMID: 36867173.