Title: Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression. The New England Journal of Medicine, 2023. Lenze, Eric J. and Mulsant, Benoit H. and Roose, Steven P. et al
Type of Study: This study was an RCT that studied the benefit of augmenting or switching antidepressants in older patients who are treatment-resistant to depression as an extensive study like this has not been done before.
Overview: The researchers conducted a two-step open-label trial that involved adults 60 years of age and older who were treatment resistant to depression. Treatment-resistant depression was defined as a lack of remission of major depression after two or more trial use of antidepressants which was determined using PHQ-9. A score of 10 or more was needed for participants to take part in this study. 6,119 patients were approached for this trial, 1055 passed prescreening stages, and from there 867 participants underwent randomization. Participants were randomly assigned to a Step 1, 1:1:1 ratio to augmentation of their existing medication with aripiprazole starting at 2.5mg per day and increasing to a max dose of 15 mg per day. Augmentation of their existing medication with extended-release bupropion (starting at 150 mg per day, with a target of 300 mg per day and a maximum of 450 mg per day) (bupropion-augmentation group), or a taper of their current antidepressant and a switch to extended-release bupropion.
Outcome: The study lasted from 2/22/2017 to 12/31/2019. Step 1 had 619 patients enrolled and from there 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. The well-being scores improved by 4.3 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. Remission was seen in 8.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. For step 2, 248 patients were enrolled 127 were assigned to lithium augmentation and 121 were switched to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively. Remission occurred in 18.9% of patients in the lithium augmentation group, and 21.5% in the switch to nortriptyline group.
Conclusion: The researchers found that augmenting existing antidepressants with aripiprazole improved the well-being significantly over 10 weeks than a switch to bupropion and was associated higher incidence of remission. Lithium augmentation and a switch to nortriptyline were effective, and safe in patients who did not have a response to their assigned treatment in step 1. The results suggest that aripiprazole augmentation can be a better overall antidepressant strategy than bupropion augmentation or a switch to bupropion. The study does have certain limitations such as the study had no placebo group. Adherence to treatment strategies was in the range of 50-70%. Additionally, findings do not apply to other augmentation or other options. The other limitation was that patients were aware of what step they were in and could’ve been reacting positively to receiving two drugs than one.
