Anti-inflammatory interventions for the treatment and prevention of depression among older adults: a systematic review and meta-analysis

Abstract

Recent evidence from clinical and animal studies with anti-inflammatory agents in depression is conflicting. One possible reason is the heterogeneity of baseline inflammation levels. Since older adults are generally associated with chronic low-grade inflammation and depression is one of the most common mental disorders in this population, this meta-analysis aimed to evaluate the therapeutic and preventative effects of anti-inflammatory interventions for depression among older adults. PubMed, Cochrane Library, Embase, and PsycINFO were searched for randomized controlled trials (RCTs) up to November 18, 2024. The primary outcomes were mean change scores of depression scores and incidences of depression after treatment. Pooled standard mean differences (SMDs) and odds ratios (ORs) including 95% confidence intervals (95% CI) were calculated. Of 3116 screened articles, 31 RCTs met the inclusion criteria, with 25 studies investigating efficacy and 7 studies investigating the incidence following anti-inflammatory treatment. Anti-inflammatory interventions were statistically significantly more effective than placebo in reducing depressive scores for older adults with depression (SMD = -0.57, 95% CI = -0.98 to -0.15, p = 0.008). Sub-group analyses supported the use of omega-3 fatty acids (SMD = -0.14, 95% CI = -0.27 to -0.02, p = 0.03) and botanical drug or dietary intervention (SMD = -0.86, 95% CI = -1.58 to -0.13, p = 0.02) among older participants. While limited by substantial heterogeneity among included studies, these results reveal the moderate beneficial effects of anti-inflammatory interventions for the treatment and prevention of depression among older adults. Future high-quality RCTs are warranted to determine which anti-inflammatory interventions are most preferential for older patients with depression.

Fig. 1. PRISMA flow chart of study selection.

Of the 3116 relevant studies, 472 were excluded due to duplication, 2508 were excluded because their titles and abstracts did not meet the criteria, and 105 studies were excluded following full-text screening. 31 RCTs were finally included. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses. *One article reported both the score changes of depressive symptoms and the numbers of patients with severe depressive symptoms after treatment, thus this study was included in the meta-analyses of the treatment and prevention of depression.

Fig. 2. Forest plots showing summary effect sizes for the primary efficacy outcomes.

A Meta-analysis of anti-inflammatory interventions vs. placebo in older patients with depression. B Meta-analysis of anti-inflammatory interventions vs. active control in older patients with depression. C Meta-analysis of anti-inflammatory interventions vs. placebo in non-depressed elderly adults. SD standard deviation, CI confidence interval.

Fig. 3. Forest plots showing summary effect sizes for the prevention outcomes of anti-inflammatory interventions in older adults.

CI confidence interval.

Fig. 4. Antidepressant activity of anti-inflammatory interventions vs. placebo.

SD standard deviation, CI confidence interval, NSAID nonsteroidal anti-inflammatory drugs, FA fatty acid.

Fig. 5. Forest plots showing summary effect sizes for the secondary efficacy outcomes.

A Meta-analysis of anti-inflammatory interventions on mental health quality in older participants. B Meta-analysis of anti-inflammatory interventions on response rate in older participants. SD standard deviation, CI confidence interval.

Fig. 6. All-cause discontinuation of anti-inflammatory interventions of the included studies.

CI confidence interval, NSAID nonsteroidal anti-inflammatory drugs, FA fatty acid.