Tien-Wei Hsu1, Brendon Stubbs2, Chih-Sung Liang3, Tien-Yu Chen4, Ta-Chuan Yeh5, Chih-Chuan Pan1, Che-Sheng Chu6. 1. Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. 2. Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK; Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK. 3. Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. 4. Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. 5. Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan. 6. Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Center for Geriatric and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Non-invasive Neuromodulation Consortium for Mental Disorders, Society of Psychophysiology, Taipei, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: cschu@vghks.gov.tw.
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.
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.
Authors: Kurt Kroenke; Sujuan Gao; Kelly M Mosesso; Susan E Hickman; Laura R Holtz; Alexia M Torke; Nina M Johnson; Greg A Sachs Journal: J Palliat Med Date: 2022-03-29 Impact factor: 2.947