Antidepressant augmentation improved well-being compared with switch in adults with TRD

In older adults with treatment-resistant depression, antidepressant augmentation improved well-being significantly over 10 weeks compared with switching medications and was associated with higher incidence of remission.

“Major depression is common in older adults and often persists despite appropriate treatment with first-line antidepressants,” Eric J. Lenze, MD, head of the department of psychiatry at Washington University School of Medicine, and colleagues wrote in the New England Journal of Medicine. “Pharmacologic strategies for treatment-resistant depression include augmentation ... and the replacement of an antidepressant with one from a different class.”

Lenze and colleagues aimed to assess benefits and risks of augmenting or switching antidepressants in older adults with TRD.

They conducted a two-step, open-label trial at five universities (four in the United States, one in Canada) including participants aged 60 years and older. In step one, 619 individuals were randomized on a 1:1:1 basis to receive either aripiprazole augmentation (n = 211), bupropion augmentation (n = 206) or switching from existing antidepressants to bupropion (n = 202). Those deemed ineligible or did not show improvement in step one were subsequently enrolled in step two and randomized on a 1:1 basis to receive either augmentation with lithium (n = 127) or a switch to nortriptyline (n = 121). Each step lasted approximately 10 weeks, with the primary outcome a change from baseline in psychological well-being, assessed by the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales, where higher scores indicate greater well-being. Remission of depression was a secondary outcome.

For step one, researchers found 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 bupropion switch group was 2.79 points (95% CI, 0.56-5.02); between-group differences were not significant for aripiprazole augmentation compared with bupropion augmentation or for bupropion augmentation compared with bupropion switch. In aripiprazole augmentation cohort, remission occurred in 28.9% of participants, 28.2% in the bupropion-augmentation group and 19.3% in the bupropion switch group.

For step two, data showed well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, 1.92-3.91). Remission occurred in 18.9% of lithium-augmentation participants and 21.5% in the nortriptyline switch group.

“These findings warrant further examination to inform prevention strategies,” Lenze and colleagues wrote.