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Low-dose aspirin did not prevent depression among older adults, according to a substudy of the ASPREE trial.

Among 19,114 adults 65 and over, incidence of depression was 70.4 events per 1,000 person-years among patients randomized to 100-mg daily aspirin and 69.1 per 1,000 person-years for patients on placebo, at a median 4.7 years follow-up, reported Michael Berk, MBBCH, PhD, of Deakin University in Victoria, Australia, and colleagues.

Overall, no significant difference was observed in the risk of depression between groups, measured as a score of 8 or more on the Center for Epidemiologic Studies Depression 10-item (CES-D-10) scale (HR 1.02, 95% CI 0.96-1.08, P=0.54), although there was an increased rate of bleeding among the aspirin group, they wrote in .

This study was undertaken to test the "inflammatory hypothesis for depression," Berk told 番茄社区app in an email, noting that the dose of aspirin used in this study was relatively low, and that many other anti-inflammatory strategies, including cox inhibitors, minocycline (Minocin), and statins "remain promising."

"Inflammation is a complex process with many elements, and we don't have a good understanding regarding the precise optimal targets in inflammation," Berk said.

The relationship between depression and chronic physiological conditions is mood disorders have been linked with elevated levels of circulating inflammatory proteins, and patients with chronic inflammatory conditions are also more likely to have depression.

Although the study showed low-dose aspirin was not protective against depression in older adults, it is not necessarily the last word on the inflammatory hypothesis for depression, commented Charles Raison, MD, of the University of Wisconsin Madison, who was not involved in this study.

There may be subgroups of people with depression with elevated baseline inflammation for whom anti-inflammatory agents might be more effective, Raison said. Aspirin also has off-target effects that may have negated any benefit, but without measuring things like blood viscosity and C-reactive proteins, both of these hypotheses remain unclear, he added.

"Depression is heterogenous and there is some evidence you have to have high inflammation to get the benefits of anti-inflammatory [agents]," Raison told 番茄社区app.

The ASPREE-D trial was conducted among older, healthy adults in Australia and the U.S., whose depression levels were assessed annually. Patients with a cardiovascular history, elevated bleeding risk, or uncontrolled hypertension were excluded.

The cohort (mean age 75; 56.4% female) was overwhelmingly white (93.5%) and English-speaking (95.6%). The proportion of patients in the aspirin versus placebo group with baseline scores of 8 or more was slightly lower (9.7% vs 9.9%) while the proportion diagnosed with depression was similar between groups (about 12%), the authors reported. The mean CES-D-10 score was 3.2 in both groups.

Overall, patients in both groups actually had higher scores on the CES-D-10 at their annual visits than at baseline, with the proportion of participants with scores of 8 or more nearly doubling at the end of follow-up, although the changes were not significant between groups, researchers reported.

No significant differences were observed between the aspirin and placebo cohorts in 12-Item Short Form Survey (SF-12) mental scores (difference 0.0-0.3 points) or hospitalizations associated with depression (0.35% vs 0.26%), throughout the follow up either, they noted.

The cohort recruited for this study had indicators of a higher baseline quality of life, such as reduced smoking rates, compared with the general older population, which may limit the generalizability of the study's findings, the authors reported. A 100-mg dose of aspirin may have also been too low to access any psychiatric benefit, they added.

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