Augmenting Vs. Switching Antidepressant for Treatment Resistant Depression in Older adults: Results from the Optimum Study

Abstract

This symposium will provide new information from a large, recently-completed comparative effectiveness trial called “OPTIMUM”, which studied augmentation vs. switch strategies for Treatment Resistant Depression (TRD) in older adults, yielding practical recommendations for treatment. Treatment resistance is common in older depressed adults, as ∼30% fail to remit with first-line antidepressant pharmacotherapies; namely SSRIs and SNRIs. Next-line strategies for TRD include augmentation with aripiprazole, augmentation with bupropion, and switch to bupropion. For those with higher levels of treatment resistance, older but well-known strategies are lithium augmentation and a switch to a secondary amine tricyclic (namely nortriptyline). Understanding the benefits vs. risk of these medication strategies is crucial for this population, which has high morbidity from depression but also significant risks from pharmacotherapy. The "Optimizing antidepressants for TRD in older adults" (OPTIMUM) study, funded by the Patient-Centered Outcomes Research Institute, is a 5-center collaboration that randomized 744 depressed individuals aged 60+ with TRD. It is the largest-ever clinical trial of TRD in older adults, with a similar design as the STAR*D and VAST-D studies that were conducted in younger adults. The OPTIMUM trial was a pragmatic trial conducted in the community, using measurement-based care support from the OPTIMUM team to guide patients through treatment. The study found that augmentation with aripiprazole and augmentation with bupropion had roughly similar effectiveness, and were more effective than switch to bupropion; in contrast, all three of these strategies were roughly equal in their risks such as falls and serious adverse events. In the second step of the trial, lithium augmentation and a switch to nortriptyline were roughly equivalent in both effectiveness and risks. After presenting the data on effectiveness and risk from this trial, the symposium speakers will distill these findings into practical recommendations for physicians in treating older adults and describe remaining, unmet challenges in our understanding of TRD treatment in older adults.