Effect of aspirin on long-term management of depression

May 6, 2021

Analysis shows aspirin’s potential adverse effect on mood in older adults with pre-existing depression


Late-life depression is common, yet is often mistaken as a normal part of ageing. For older adults who are diagnosed, treatment is often inadequate.

Inflammation is long thought to play a role in depression. In 2020, the ASPREE -D (Depression) sub-study reported aspirin’s anti-inflammatory properties had no overall effect on mood in 19,114 healthy older adults in Australia and the US, mostly aged 70 or more.

However, a recent analysis of data from a small sub-group of ASPREE participants – those with depression, or a history of depression at enrolment into ASPREE – suggests aspirin might actually make depressive symptoms worse for some older adults.

This new and previously unknown potential effect of aspirin in healthy older adults was published in the journal Molecular Psychiatry.

Man with glasses is dressed in black jacket and blue shirt

Above: lead author, Prof Michael Berk, Alfred Deakin Professor Centre: School of Medicine Area: Barwon Health, led the ASPREE-D sub-study and this analysis.

Pre-existing depression:

ASPREE researchers examined data from 1879 participants who were depressed at entry into the aspirin trial, with 925 in the aspirin group and 954 in the placebo group.

Over an average of 4.7 years, differences in mood emerged.

Researchers found aspirin intake was associated with a significant increase of more severe and persistent symptoms of depression, as well as a reduction in mental health quality of life scores, compared to those in the placebo group.

The largest effect of aspirin on mood occurred during the first year after enrolment and in individuals with more severe depressive symptoms at study entry.

Findings were unaffected by gender, age, smoking status, alcohol consumption, abdominal circumference or body mass (BMI).

The number of hospitalisations for depression during the study period was the same for both groups.

Antidepressant use:

Glass water, pill box and an open hand with 3 tablets laid on the palm, in front of blue background

Image by Towfiqu Barbhuiya – unsplash

Of the 1879 participants depressed at enrolment, 456 took an antidepressant, with 25.2% in the aspirin group and 23.4% in the placebo group.

Antidepressants did not modify the effect of aspirin on mood. The analysis showed aspirin intake was still significantly associated with worsening depressive symptoms, suggesting a possible interaction between the two drugs.

While both groups showed an increase in antidepressant use over the duration of the trial, more participants in the aspirin group took antidepressants than in the placebo group (36.7% versus 33.9%).

Study conduct:

ASPREE participants were generally in good health, were living independently at enrolment into the trial, and were without known heart disease, persistent physical disability or dementia.  All participants were randomly assigned 100mg aspirin or a matched placebo tablet for the duration of the trial.  Participants, researchers and GPs were blinded to the assigned ASPREE tablet.

Information on the severity of depressive symptoms was collected using a validated self-reporting scale, the CESD-10, which participants completed at study entry and annually thereafter.

Study participants also self-rated their psychological wellbeing in a Quality of Life Short Form 12 (SF-12) questionnaire at enrolment and annually.

Researchers compared averaged CESD-10 and mental health component of SF-12 scores between aspirin and placebo groups at study entry and at each annual visit.

The average CESD-10 scores in the aspirin group changed significantly in the first year compared to the placebo group and continued to be slightly higher for the reminder of the trial.

Hear from the lead author:

Lead author Prof Michael Berk said findings from the analysis indicate that aspirin may worsen depressive symptoms for some older adults.

“While this study failed to demonstrate any benefit of aspirin into the course of depression, we have identified an adverse effect of aspirin in older adults with pre-existing depressive symptoms,” said Prof Berk.

“Additionally, aspirin does appear to interact with anti-depressant medication, possibly through altering the microbiome or gut permeability.”

Prof Berk said the study put mental health outcomes from prescribed medications under the spotlight.

“As our study was in older adults, who did not have a medical need to take aspirin, findings are only applicable to healthy adults, mostly aged over 70 years,” said Prof Berk.

“We encourage anyone experiencing symptoms of depression to speak to their doctor and to seek medical advice before stopping or starting daily low dose aspirin.”

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