Systematic review of clinical effectiveness of interventions for treatment resistant late-life depression.
Ageing research reviews May 1, 2025 Beatriz Pozuelo Moyano, Denise Gomez Bautista, Karla Jocelyn Porras Ibarra et al. 12 citations
Nearly half of older adults with major depression have treatment-resistant late-life depression (TRLLD). A systematic review of randomized controlled trials up to March 2024 found that aripiprazole (based on two studies), venlafaxine, ketamine, and lithium were associated with reduced depressive symptoms after treatment. Among non-pharmacological approaches, repetitive transcranial magnetic stimulation, sequential bilateral theta burst stimulation, and cognitive remediation also showed significant improvements. However, the quality of evidence ranged from very low to medium, and most studies had small sample sizes. Aripiprazole augmentation appears effective with an acceptable side effect profile, but other treatments lack strong evidence. Large-scale trials are needed for firm conclusions.