Systematic review of clinical effectiveness of interventions for treatment resistant late-life depression.
Beatriz Pozuelo Moyano, Denise Gomez Bautista, Karla Jocelyn Porras Ibarra, Christoph Mueller, Armin Von Gunten, Pierre Vandel, Setareh Ranjbar, Robert Howard, Allan H. Young, Robert A. C. Stewart, Suzanne Reeves, Vasiliki Orgeta
Ageing Research Reviews May 1, 2025 DOI: 10.1016/j.arr.2025.102710 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Peer reviewed |
|---|---|
| Population | Older adults with treatment-resistant late-life depression |
| Interventions | antidepressants antipsychotics mood stabilizers ketamine psychotherapy electroconvulsive therapy repetitive transcranial magnetic stimulation computerized cognitive remediation |
| Topics | Depression |
| Keywords | Late life depression Older people Randomized controlled trials Geriatric mental health Depression therapy Clinical trials Antipsychotic medication |
| Citations | 12 |
| Key findings | Aripiprazole augmentation appears effective for treatment-resistant late-life depression based on two studies, but evidence for other treatments is limited and of low quality. |
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.
Comparable studies
Other systematic reviews and meta-analyses on depression, most cited first.