Efficacy of Antidepressants in Management of Depressive Symptoms in Dementia: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Background: Dementia is associated with a complex array of neuropsychiatric manifestations which require consideration as they worsen the course of illness, especially in neurodegenerative etiologies. Depression and subsyndromal depressive symptoms are common in dementia, usually managed with antidepressants, but evidence is weak. Objective: The objective is to study the efficacy of antidepressants compared to placebo in management of depressive symptoms in dementia. Methodology: Electronic databases such as PubMed, MEDLINE, PsychINFO, ClinicalTrials.gov, BASE, and MedNar were searched from their date of inception to March 18, 2024, with appropriate search-terms. Randomized controlled trials (RCTs) that are double-blind in nature with placebo as comparator of dementia patients (Alzheimer’s disease [AD], Frontotemporal, Lewy body, and Parkinson disease dementia) treated with antidepressants for at least ≥ 4 weeks with severity of depressive symptoms measured on standardized rating scales were included. Studies with nonrandomized/nondouble-blind design, active drug or brain stimulation methods as comparator and nonneurodegenerative etiologies of dementia were excluded. Cochrane tool for risk of bias assessment, Covidence and Microsoft Excel for data extraction and review manager version 5.4.1 for data analysis were used. Results: Our search yielded 13(N) RCTs for systematic review, majority of which reported on AD (n = 12), selective serotonin reuptake inhibitors as intervention (n = 7), and high risk of bias (n = 9). Efficacy analysis using forest-plot with seven RCTs showed no statistically significant treatment effect (standardized mean differences [SMD] = −0.04, 95%confidence interval [−0.36, 0.27], Z = 0.26, P = 0.79) between intervention and placebo group. Substantial significant heterogeneity (I 2 = 74%, P < 0.001) was noted across studies. Discussion: Antidepressants administered for 6–13 weeks and different rating scales used to measure outcome in RCTs were possible reasons for heterogeneity. We conclude that antidepressants have not been found to be efficacious compared to placebo in management of depressive symptoms in dementia. Findings cannot be generalized to other etiologies as our analysis found limited data majorly on AD and RCTs with high risk or some concerns in the bias, thus throws a light on need for robust RCTs in this area.