Systematic review of clinical effectiveness of interventions for treatment resistant late-life depression.

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.

Study at a glance

Abstract

Treatment-resistant late-life depression (TRLLD) affects nearly half of older adults with major depression. This systematic review evaluates published evidence of effectiveness of both pharmacological and non-pharmacological treatments for TRLLD. A search of MEDLINE, EMBASE, CINAHL, PsycINFO, the Cochrane Library, and online trial registries up to March 2024 was conducted to identify randomized controlled trials (RCTs) evaluating pharmacological and non-pharmacological interventions for TRLLD. Seven studies assessed the effectiveness of pharmacological interventions (antidepressants, antipsychotics, mood stabilizers, or ketamine) and another seven examined non-pharmacological approaches (psychotherapy, electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS), and computerized cognitive remediation). Aripiprazole (2 studies), venlafaxine (1 study), ketamine (1 study), and lithium (1 study) were associated with a reduction in depressive symptoms post-treatment compared to the comparator treatment group. rTMS (2 studies), sequential bilateral theta burst stimulation (1 study) and cognitive remediation (1 study) also showed significant improvements in depressive symptoms post-treatment compared to a comparator treatment group. Quality of evidence varied from very low to medium among the included studies. Most studies reported data on small sample sizes. We identified a small number of RCTs evaluating treatments for TRLLD. Aripiprazole augmentation appears to be an effective treatment based on two studies, with an acceptable side effect profile. Other treatments may be effective, but the evidence is based on very low-quality evidence. Future large-scale RCTs are urgently needed to draw firm conclusions.