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.

Duration of new antidepressant use and factors associated with discontinuation among community-dwelling persons with Alzheimer’s disease

“…Finnish clinical care guidelines for BPSDs suggests that need for antidepressant use should be evaluated every three to 6 months, as some BPSD symptoms can resolve by itself [24]. Due to a risk of adverse events such as falls [26], fractures, all-cause mortality, and upper gastrointestinal bleeding [8] and modest efficacy for BPSD [6,7], duration of antidepressant use should be limited when treating BPSD. Antidepressant use should be discontinued if there is no more current indication for use, due to lack of benefit, and at emergence of adverse effects or events.…”

“…However, these drugs are also used for other indications such as neuropathic pain, insomnia, and migraine. Among persons with AD, antidepressants are used for treatment of behavioral and psychological symptoms of dementia (BPSD) although their effectiveness in this indication is modest [6,7].…”

Steps Towards Developing Effective Treatments for Neuropsychiatric Disturbances in Alzheimer’s Disease: Insights From Preclinical Models, Clinical Data, and Future Directions

“…In combination, patients with both apathy and depressive behavior are less independent and have lower ADL compared to AD patients with only apathy, depressive behavior, or none of the symptoms (Benoit et al, 2012). Thus, recognizing, discriminating, and treating apathy and depressive behavior are important but in AD pharmacological treatment of apathy (Rea et al, 2014) and depressive symptoms (Orgeta et al, 2017) have proven difficult; most likely, explained by the lack of knowledge about circuits involved in the symptom development.…”

Depression and antidepressant prescribing in the elderly

“…16 Evidence for effective treatment of depression in Alzheimer's is scant with a recent meta-analysis of seven randomised controlled trials finding no significant difference between antidepressant treatment and placebo. 17 Though high-quality evidence of benefit is lacking, we would suggest that a trial of antidepressant medication is advisable and pragmatic in suitable circumstances.…”