The association between aspirin use and depression: a systematic review and meta‐analysis of observational studies

Abstract

Purpose Many clinical trials and observational studies have been conducted under the premise that the anti‐inflammatory effect of aspirin may prevent depression. These studies, however, showed inconsistent results. To inspect the association between aspirin use and depression, we conducted a meta‐analysis of observational studies. Methods In August 2019, two authors independently searched PubMed, EMBASE, and PsycINFO to retrieve observational epidemiological studies presenting an association between aspirin use and depression. Case‐control and cohort studies were included, and odds ratios (ORs) or relative risks (RRs) with 95% confidence intervals (CIs) for the risk of depression were estimated using a random‐effects model. In addition, number needed to harm (NNH) was calculated to measure the rates of depression. Results In total, 12 observational studies—five case‐control studies and seven prospective cohort studies—were included in this meta‐analysis. The random‐effects model demonstrated a significant association between aspirin use and depression (OR/RR 1.10; 95% CI: 1.05‐1.16) with insignificant heterogeneity (I2 = 23.3%). The risk estimates of depression from prospective cohort studies were similar (RR 1.11; 95% CI: 1.08‐1.14), and heterogeneity was not observed (I2 = 0.0%). In the subgroup meta‐analysis, a duration of aspirin use ≥5 years and a dosage ≥500 mg daily were also associated with depression. The NNH for depression with aspirin use >5 years was 103 (95% CI 91‐111) indicating that observed event is rare. Conclusions Aspirin use was associated with depression in the present meta‐analysis. One of the major limitations is the lack of detail and consistency with respect to exposure verification in the included papers. Another limitation is the lack of randomized controlled studies and prospective cohort studies.

Non-steroidal anti-inflammatory drug target gene associations with major depressive disorders: a Mendelian randomisation study integrating GWAS, eQTL and mQTL Data

“…Although, our study indicated a protective effect of NEU1, the use of acetylsalicylic acid to target MDD and its impact on MDD remains controversial in population-based studies [59][60][61]. Recently, an RCT involving 19,114 older adults showed that taking low-dose aspirin (acetylsalicylic acid) at 100 mg/day did not lower depression rates when compared with placebo [59].…”

Associations of Cardiovascular Agents and Metformin with Depression Symptoms: A Cross-Sectional Analysis from the HUNT Study, Norway

“…However, the authors of these studies emphasized the possibility that participant characteristics, particularly the inclusion of individuals with fewer medical comorbidities, could influence the findings [ 64 , 65 ]. Additionally, meta-analytic evidence based on observational data showed associations between ASA use and increased depression risk [ 30 ]. However, the meta-analysis included large-sample studies, participants aged ≥ 65 years, high-dose ASA users, diverse depression instruments (self-report vs clinical diagnosis), and study populations (CVDs vs no-CVDs).…”

“…Thus, inflammatory pathways may be an additional target in depression treatment [25][26][27]. Consequently, various anti-inflammatory, cardiovascular, and antidiabetic agents have been explored for putative antidepressant effects [24,[28][29][30][31][32]. To date, clinical and observational studies addressing relationships between pharmacotherapies for CVDs or DM and depression symptoms have been limited and inconsistent.…”

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“…A recent meta-analysis and a systematic review attained contradictory conclusions concerning the correlation between aspirin and depression, proving the need for more extensive trials. One of them found a positive association, although infrequent, with a number needed to harm of 103 [ 35 ]. The other one demonstrated a link between aspirin and a reduced risk of developing depression [ 36 ].…”