Systematic review of clinical effectiveness of interventions for treatment resistant late-life depression.
Ageing research reviews – May 01, 2025
Source: PubMed
Summary
When depression persists in older people despite standard treatments, new approaches offer hope. Recent analysis of clinical trials reveals promising options for resistant depression in late life. Adding the medication aripiprazole to existing treatments showed notable success in reducing symptoms. Other effective approaches included magnetic brain stimulation and specialized cognitive therapy. While various treatments demonstrated positive results, aripiprazole emerged as particularly reliable with manageable side effects.
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.