Efficacy of serotonergic antidepressant treatment for the neuropsychiatric symptoms and agitation in dementia: A systematic review and meta-analysis

Tien Wei Hsu; Brendon Stubbs; Chih Sung Liang; Tien Yu Chen; Ta Chuan Yeh; Chih Chuan Pan; Che Sheng Chu

doi:10.1016/j.arr.2021.101362

Efficacy of serotonergic antidepressant treatment for the neuropsychiatric symptoms and agitation in dementia: A systematic review and meta-analysis

Tien Wei Hsu, Brendon Stubbs, Chih Sung Liang, Tien Yu Chen, Ta Chuan Yeh, Chih Chuan Pan, Che Sheng Chu^*

^*Corresponding author for this work

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

20 Citations (Scopus)

Abstract

Objective: Serotonergic dysfunction may be involved in the etiology of overall neuropsychiatric symptoms (NPS) and agitation in patients with dementia; therefore, we aim to perform a systematic review and meta-analysis to investigate the efficacy of serotonergic antidepressants in such populations. Methods: We systematically searched PubMed, Medline, Embase, and Cochrane Library to obtain randomized controlled trials (RCTs) from the date of their inception until December 11, 2020 to examine the effect of serotonergic antidepressants on the outcomes of interest in patients with dementia. Data were pooled using a random-effects model. Co-primary outcomes were mean changes in overall NPS and agitation as a specific symptom of NPS. Secondary outcomes were mean changes in depressive symptoms, cognition, and care burden. Results: Fourteen randomized controlled trials were eligible (n = 1,374; mean age = 76.8 years; mean proportion of female = 61.9 %). Serotonergic antidepressants significantly reduced the overall NPS (k = 12, n = 1276, Hedges’ g = −0.49, 95 % confidence intervals [CIs] = -0.74 to -0.24, p < 0.001) and agitation severity (k = 9, n = 749, Hedges’ g = −0.28, 95 % CIs = −0.43 to −0.14, p < 0.001), both with small effect size in patients with dementia. For secondary outcome, serotonergic antidepressants also significantly improved depressive symptoms, cognition, and care burden with small to very small effect sizes (depressive symptoms, k = 8, n = 938, Hedges’ g = −0.32, 95 % CIs = −0.49 to −0.15, p < 0.001;cognition, k = 6, n = 983, Hedges’ g = 0.15, 95 % CIs = 0.002 to 0.29, p = 0.046; care burden, k = 7, n = 961, Hedges’ g = −0.24, 95 % CIs = −0.41 to −0.07, p = 0.005). Subgroup analysis showed that both selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs significant reduced agitation and depressive symptoms (For agitation, SSRIs, k = 6, n = 605, Hedges’ g = −0.25, 95 % CIs = −0.41 to −0.09, p=0.002; non-SSRIs, k = 3, n = 144, Hedges’ g = −0.41, 95 % CIs = −0.74 to −0.08, p = 0.016; For depression, SSRIs, k = 6, n = 736, Hedges’ g = −0.29, 95 % CIs = −0.48 to −0.09, p=0.004; non-SSRIs, k = 343, n = 144, Hedges’ g = −0.43, 95 % CIs = −0.78 to −0.09, p = 0.016), whereas only SSRIs reduced overall NPS (k = 9, n = 1109, Hedges’ g = −0.49, 95 % CIs = −0.78 to −0.20, p = 0.001) and care burden (k = 5, n = 740, Hedges’ g = −0.29, 95 % CIs = −0.50 to −0.08, p=0.007). Conclusion: The present meta-analysis indicates that serotonergic antidepressants effectively alleviate overall NPS, agitation, depressive symptoms, and care burden, and improve cognitive function.

Original language	English
Article number	101362
Journal	AGEING RESEARCH REVIEWS
Volume	69
DOIs	https://doi.org/10.1016/j.arr.2021.101362
Publication status	Published - Aug 2021

Keywords

Agitation
Antidepressant
Dementia
Neuropsychiatric symptoms
Selective serotonin reuptake inhibitor

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10.1016/j.arr.2021.101362

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@article{a3092d2a9ec34b38bd6fb4c7cbbca6f2,

title = "Efficacy of serotonergic antidepressant treatment for the neuropsychiatric symptoms and agitation in dementia: A systematic review and meta-analysis",

abstract = "Objective: Serotonergic dysfunction may be involved in the etiology of overall neuropsychiatric symptoms (NPS) and agitation in patients with dementia; therefore, we aim to perform a systematic review and meta-analysis to investigate the efficacy of serotonergic antidepressants in such populations. Methods: We systematically searched PubMed, Medline, Embase, and Cochrane Library to obtain randomized controlled trials (RCTs) from the date of their inception until December 11, 2020 to examine the effect of serotonergic antidepressants on the outcomes of interest in patients with dementia. Data were pooled using a random-effects model. Co-primary outcomes were mean changes in overall NPS and agitation as a specific symptom of NPS. Secondary outcomes were mean changes in depressive symptoms, cognition, and care burden. Results: Fourteen randomized controlled trials were eligible (n = 1,374; mean age = 76.8 years; mean proportion of female = 61.9 %). Serotonergic antidepressants significantly reduced the overall NPS (k = 12, n = 1276, Hedges{\textquoteright} g = −0.49, 95 % confidence intervals [CIs] = -0.74 to -0.24, p < 0.001) and agitation severity (k = 9, n = 749, Hedges{\textquoteright} g = −0.28, 95 % CIs = −0.43 to −0.14, p < 0.001), both with small effect size in patients with dementia. For secondary outcome, serotonergic antidepressants also significantly improved depressive symptoms, cognition, and care burden with small to very small effect sizes (depressive symptoms, k = 8, n = 938, Hedges{\textquoteright} g = −0.32, 95 % CIs = −0.49 to −0.15, p < 0.001;cognition, k = 6, n = 983, Hedges{\textquoteright} g = 0.15, 95 % CIs = 0.002 to 0.29, p = 0.046; care burden, k = 7, n = 961, Hedges{\textquoteright} g = −0.24, 95 % CIs = −0.41 to −0.07, p = 0.005). Subgroup analysis showed that both selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs significant reduced agitation and depressive symptoms (For agitation, SSRIs, k = 6, n = 605, Hedges{\textquoteright} g = −0.25, 95 % CIs = −0.41 to −0.09, p=0.002; non-SSRIs, k = 3, n = 144, Hedges{\textquoteright} g = −0.41, 95 % CIs = −0.74 to −0.08, p = 0.016; For depression, SSRIs, k = 6, n = 736, Hedges{\textquoteright} g = −0.29, 95 % CIs = −0.48 to −0.09, p=0.004; non-SSRIs, k = 343, n = 144, Hedges{\textquoteright} g = −0.43, 95 % CIs = −0.78 to −0.09, p = 0.016), whereas only SSRIs reduced overall NPS (k = 9, n = 1109, Hedges{\textquoteright} g = −0.49, 95 % CIs = −0.78 to −0.20, p = 0.001) and care burden (k = 5, n = 740, Hedges{\textquoteright} g = −0.29, 95 % CIs = −0.50 to −0.08, p=0.007). Conclusion: The present meta-analysis indicates that serotonergic antidepressants effectively alleviate overall NPS, agitation, depressive symptoms, and care burden, and improve cognitive function.",

keywords = "Agitation, Antidepressant, Dementia, Neuropsychiatric symptoms, Selective serotonin reuptake inhibitor",

author = "Hsu, {Tien Wei} and Brendon Stubbs and Liang, {Chih Sung} and Chen, {Tien Yu} and Yeh, {Ta Chuan} and Pan, {Chih Chuan} and Chu, {Che Sheng}",

note = "Funding Information: This work was supported by grant number VGHKS107-026 from Kaohsiung Veterans General Hospital . Publisher Copyright: {\textcopyright} 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = aug,

doi = "10.1016/j.arr.2021.101362",

language = "English",

volume = "69",

journal = "AGEING RESEARCH REVIEWS",

issn = "1568-1637",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Efficacy of serotonergic antidepressant treatment for the neuropsychiatric symptoms and agitation in dementia

T2 - A systematic review and meta-analysis

AU - Hsu, Tien Wei

AU - Stubbs, Brendon

AU - Liang, Chih Sung

AU - Chen, Tien Yu

AU - Yeh, Ta Chuan

AU - Pan, Chih Chuan

AU - Chu, Che Sheng

N1 - Funding Information: This work was supported by grant number VGHKS107-026 from Kaohsiung Veterans General Hospital . Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/8

Y1 - 2021/8

N2 - Objective: Serotonergic dysfunction may be involved in the etiology of overall neuropsychiatric symptoms (NPS) and agitation in patients with dementia; therefore, we aim to perform a systematic review and meta-analysis to investigate the efficacy of serotonergic antidepressants in such populations. Methods: We systematically searched PubMed, Medline, Embase, and Cochrane Library to obtain randomized controlled trials (RCTs) from the date of their inception until December 11, 2020 to examine the effect of serotonergic antidepressants on the outcomes of interest in patients with dementia. Data were pooled using a random-effects model. Co-primary outcomes were mean changes in overall NPS and agitation as a specific symptom of NPS. Secondary outcomes were mean changes in depressive symptoms, cognition, and care burden. Results: Fourteen randomized controlled trials were eligible (n = 1,374; mean age = 76.8 years; mean proportion of female = 61.9 %). Serotonergic antidepressants significantly reduced the overall NPS (k = 12, n = 1276, Hedges’ g = −0.49, 95 % confidence intervals [CIs] = -0.74 to -0.24, p < 0.001) and agitation severity (k = 9, n = 749, Hedges’ g = −0.28, 95 % CIs = −0.43 to −0.14, p < 0.001), both with small effect size in patients with dementia. For secondary outcome, serotonergic antidepressants also significantly improved depressive symptoms, cognition, and care burden with small to very small effect sizes (depressive symptoms, k = 8, n = 938, Hedges’ g = −0.32, 95 % CIs = −0.49 to −0.15, p < 0.001;cognition, k = 6, n = 983, Hedges’ g = 0.15, 95 % CIs = 0.002 to 0.29, p = 0.046; care burden, k = 7, n = 961, Hedges’ g = −0.24, 95 % CIs = −0.41 to −0.07, p = 0.005). Subgroup analysis showed that both selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs significant reduced agitation and depressive symptoms (For agitation, SSRIs, k = 6, n = 605, Hedges’ g = −0.25, 95 % CIs = −0.41 to −0.09, p=0.002; non-SSRIs, k = 3, n = 144, Hedges’ g = −0.41, 95 % CIs = −0.74 to −0.08, p = 0.016; For depression, SSRIs, k = 6, n = 736, Hedges’ g = −0.29, 95 % CIs = −0.48 to −0.09, p=0.004; non-SSRIs, k = 343, n = 144, Hedges’ g = −0.43, 95 % CIs = −0.78 to −0.09, p = 0.016), whereas only SSRIs reduced overall NPS (k = 9, n = 1109, Hedges’ g = −0.49, 95 % CIs = −0.78 to −0.20, p = 0.001) and care burden (k = 5, n = 740, Hedges’ g = −0.29, 95 % CIs = −0.50 to −0.08, p=0.007). Conclusion: The present meta-analysis indicates that serotonergic antidepressants effectively alleviate overall NPS, agitation, depressive symptoms, and care burden, and improve cognitive function.

AB - Objective: Serotonergic dysfunction may be involved in the etiology of overall neuropsychiatric symptoms (NPS) and agitation in patients with dementia; therefore, we aim to perform a systematic review and meta-analysis to investigate the efficacy of serotonergic antidepressants in such populations. Methods: We systematically searched PubMed, Medline, Embase, and Cochrane Library to obtain randomized controlled trials (RCTs) from the date of their inception until December 11, 2020 to examine the effect of serotonergic antidepressants on the outcomes of interest in patients with dementia. Data were pooled using a random-effects model. Co-primary outcomes were mean changes in overall NPS and agitation as a specific symptom of NPS. Secondary outcomes were mean changes in depressive symptoms, cognition, and care burden. Results: Fourteen randomized controlled trials were eligible (n = 1,374; mean age = 76.8 years; mean proportion of female = 61.9 %). Serotonergic antidepressants significantly reduced the overall NPS (k = 12, n = 1276, Hedges’ g = −0.49, 95 % confidence intervals [CIs] = -0.74 to -0.24, p < 0.001) and agitation severity (k = 9, n = 749, Hedges’ g = −0.28, 95 % CIs = −0.43 to −0.14, p < 0.001), both with small effect size in patients with dementia. For secondary outcome, serotonergic antidepressants also significantly improved depressive symptoms, cognition, and care burden with small to very small effect sizes (depressive symptoms, k = 8, n = 938, Hedges’ g = −0.32, 95 % CIs = −0.49 to −0.15, p < 0.001;cognition, k = 6, n = 983, Hedges’ g = 0.15, 95 % CIs = 0.002 to 0.29, p = 0.046; care burden, k = 7, n = 961, Hedges’ g = −0.24, 95 % CIs = −0.41 to −0.07, p = 0.005). Subgroup analysis showed that both selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs significant reduced agitation and depressive symptoms (For agitation, SSRIs, k = 6, n = 605, Hedges’ g = −0.25, 95 % CIs = −0.41 to −0.09, p=0.002; non-SSRIs, k = 3, n = 144, Hedges’ g = −0.41, 95 % CIs = −0.74 to −0.08, p = 0.016; For depression, SSRIs, k = 6, n = 736, Hedges’ g = −0.29, 95 % CIs = −0.48 to −0.09, p=0.004; non-SSRIs, k = 343, n = 144, Hedges’ g = −0.43, 95 % CIs = −0.78 to −0.09, p = 0.016), whereas only SSRIs reduced overall NPS (k = 9, n = 1109, Hedges’ g = −0.49, 95 % CIs = −0.78 to −0.20, p = 0.001) and care burden (k = 5, n = 740, Hedges’ g = −0.29, 95 % CIs = −0.50 to −0.08, p=0.007). Conclusion: The present meta-analysis indicates that serotonergic antidepressants effectively alleviate overall NPS, agitation, depressive symptoms, and care burden, and improve cognitive function.

KW - Agitation

KW - Antidepressant

KW - Dementia

KW - Neuropsychiatric symptoms

KW - Selective serotonin reuptake inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85106254728&partnerID=8YFLogxK

U2 - 10.1016/j.arr.2021.101362

DO - 10.1016/j.arr.2021.101362

M3 - Review article

AN - SCOPUS:85106254728

SN - 1568-1637

VL - 69

JO - AGEING RESEARCH REVIEWS

JF - AGEING RESEARCH REVIEWS

M1 - 101362

ER -

Efficacy of serotonergic antidepressant treatment for the neuropsychiatric symptoms and agitation in dementia: A systematic review and meta-analysis

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