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

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.