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

European Task Force for treatment resistant depression in older people

doi:10.1016/j.arr.2025.102710

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

European Task Force for treatment resistant depression in older people

Research output: Contribution to journal › Review article › peer-review

2 Citations (Scopus)

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS AND IMPLICATIONS: 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.

Original language	English
Article number	102710
Pages (from-to)	102710
Journal	AGEING RESEARCH REVIEWS
Volume	107
Early online date	28 Feb 2025
DOIs	https://doi.org/10.1016/j.arr.2025.102710 https://doi.org/10.1016/j.arr.2025.102710
Publication status	Published - May 2025

Keywords

Late life depression
Older people
Randomized controlled trials
Resistant depression
Treatment

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@article{45f7f5beef36431ca154a2e36f8158d7,

title = "Systematic review of clinical effectiveness of interventions for treatment resistant late-life depression",

abstract = "BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS AND IMPLICATIONS: 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.",

keywords = "Late life depression, Older people, Randomized controlled trials, Resistant depression, Treatment",

author = "{European Task Force for treatment resistant depression in older people} and Moyano, {Beatriz Pozuelo} and Bautista, {Denise Gomez} and {Porras Ibarra}, {Karla Jocelyn} and Christoph Mueller and {von Gunten}, Armin and Pierre Vandel and Setareh Ranjbar and Robert Howard and Young, {Allan H} and Robert Stewart and Suzanne Reeves and Vasiliki Orgeta",

year = "2025",

month = may,

doi = "10.1016/j.arr.2025.102710",

language = "English",

volume = "107",

pages = "102710",

journal = "AGEING RESEARCH REVIEWS",

issn = "1568-1637",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Systematic review of clinical effectiveness of interventions for treatment resistant late-life depression

AU - European Task Force for treatment resistant depression in older people

AU - Moyano, Beatriz Pozuelo

AU - Bautista, Denise Gomez

AU - Porras Ibarra, Karla Jocelyn

AU - Mueller, Christoph

AU - von Gunten, Armin

AU - Vandel, Pierre

AU - Ranjbar, Setareh

AU - Howard, Robert

AU - Young, Allan H

AU - Stewart, Robert

AU - Reeves, Suzanne

AU - Orgeta, Vasiliki

PY - 2025/5

Y1 - 2025/5

N2 - BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS AND IMPLICATIONS: 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.

AB - BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS AND IMPLICATIONS: 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.

KW - Late life depression

KW - Older people

KW - Randomized controlled trials

KW - Resistant depression

KW - Treatment

UR - http://www.scopus.com/inward/record.url?scp=86000137067&partnerID=8YFLogxK

U2 - 10.1016/j.arr.2025.102710

DO - 10.1016/j.arr.2025.102710

M3 - Review article

C2 - 40024346

SN - 1568-1637

VL - 107

SP - 102710

JO - AGEING RESEARCH REVIEWS

JF - AGEING RESEARCH REVIEWS

M1 - 102710

ER -

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

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