Finally, New Hope for the Treatment of LLTRD

Late-life treatment resistant depression (LLTRD) is defined as having failed 2 adequate trials of antidepressant treatments, and is common (up to 50%) in older adults suffering from depression 1 Lenze EJ Sheffrin M Driscoll HC et al. Incomplete response in late-life depression: getting to remission. Dialogues Clin Neurosci. 2008; 10: 419-430 Crossref PubMed Google Scholar . Under or untreated LLTRD is associated with poor long-term outcomes such as cognitive dysfunction, disability, and increased risk for suicide 2 Byers AL Yaffe K. Depression and risk of developing dementia. Nat Rev Neurol. 2011; 7: 323-331 Crossref PubMed Scopus (715) Google Scholar , 3 Diniz BS Butters MA Albert SM Dew MA Reynolds 3rd, CF Late-life depression and risk of vascular dementia and Alzheimer's disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry. 2013; 202: 329-335 Crossref PubMed Scopus (808) Google Scholar , 4 Wolkowitz OM Reus VI Mellon SH. Of sound mind and body: depression, disease, and accelerated aging. Dialogues Clin Neurosci. 2011; 13: 25-39 Crossref PubMed Google Scholar . With the recent publication of the results from the OPTIMUM study, the evidence-based treatment of TRD 5 Lenze EJ Mulsant BH Roose SP et al. Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression. N Engl J Med. 2023; 388: 1067-1079 Crossref PubMed Scopus (8) Google Scholar has essentially been defined. This study entered 619 patients >60 years with TRD that were first randomly assigned (Step 1) to one of the following for 10 weeks: 1) augment their current antidepressant with aripiprazole (up to 15 mg/day), 2) augment their current antidepressant with bupropion (up to 450 mg/day), or 3) switch their current antidepressant to bupropion 450 mg/day. If the remission criteria of a MADRS score <10 were not met after Step 1, patients entered Step 2 and were randomly assigned to receive lithium augmentation or nortriptyline adjusted to a therapeutic plasma level. 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. Aripiprazole augmentation was associated with lower fall risk compared to bupropion augmentation. In Step 2, there were no differences in remission rates or falls. Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group.