Efficacy of Antidepressants for Depression in Alzheimer's Disease: Systematic Review and Meta-Analysis

Abstract

Background: Depression is common in people with Alzheimer's disease (AD) affecting overall outcomes and decreasing quality of life. Although depression in AD is primarily treated with antidepressants, there are few randomized controlled trials (RCTs) assessing efficacy and results have been conflicting.

Objectives: To systematically review evidence on efficacy of antidepressant treatments for depression in AD.

Methods: Systematic review and meta-analysis of double blind RCTs comparing antidepressants versus placebo for depression in AD. We searched MEDLINE, CINAHL, EMBASE, PsycINFO, the Cochrane Controlled Trials Register and on line national and international registers. Primary outcomes were treatment response and depressive symptoms. Secondary outcomes were cognition, acceptability, and tolerability. Risk of bias was also assessed.

Results: Seven studies met inclusion criteria. Three compared sertraline with placebo; one compared both sertraline and mirtazapine to placebo; imipramine, fluoxetine, and clomipramine were evaluated in one study each. In terms of response to treatment (6 studies, 297 patients treated with antidepressants and 223 with placebo), no statistically significant difference between antidepressants and placebo was found (odds ratio (OR) 1.95, 95% CI 0.97-3.92). We found no significant drug-placebo difference for depressive symptoms (5 studies, 311 patients, SMD -0.13; 95% CI -0.49 to 0.24). Overall quality of the evidence was moderate because of methodological limitations in studies and the small number of trials.

Conclusion: Despite the importance of depression in people with AD, few RCTs are available on efficacy of antidepressants, limiting clear conclusions of their potential role. There is a need for further high quality RCTs.

Keywords: Alzheimer’s disease; Antidepressants; depression; effectiveness; meta-analysis; randomized controlled trials.

Fig.1

Flow diagram of the review.

Fig.2

Forest plot of comparison of antidepressants versus placebo: Response to treatment (6–13 weeks).

Fig.3

Forest plot of comparison of antidepressants versus placebo: Mean depression scores (6–13 weeks).

Fig.4

Forest plot of comparison of antidepressants versus placebo: Cognition MMSE scores (6–13 weeks).

Fig.5

Forest plot of comparison of antidepressants versus placebo: Acceptability Number of drop-outs (6–13 weeks).

Fig.6

Forest plot of comparison of antidepressants versus placebo: Tolerability Number of adverse events (6–13 weeks).

Fig.7

Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies.