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Effects of aspirin on the long-term management of depression in older people: a double-blind randomised placebo-controlled trial


Late-life depression is common and often inadequately managed using existing therapies. Depression is also associated with increased markers of inflammation, suggesting a potential role for anti-inflammatory agents. ASPREE-D is a sub-study of ASPREE, a large multi-centre, population-based, double-blind, placebo-controlled trial of aspirin vs placebo in older Australian and American adults (median follow-up: 4.7 years) of whom 1879 were depressed at baseline. Participants were given 100 mg daily dose of aspirin or placebo. Depressive symptoms were assessed annually using the validated, self-rated short version of the Center for Epidemiological Studies Depression scale. There was a significant increase in depressive scores (0.6; 95% CI 0.2 to 0.9; χ2 (1) = 10.37; p = 0.001) and a decreased score in the mental health component of a quality of life scale (–0.7; 95% CI –1.4 to –0.1; χ2 (1) = 4.74; p = 0.029) in the aspirin group compared to the placebo group. These effects were greater in the first year of follow-up and persisted throughout the study, albeit with small to very small effect sizes. This study failed to demonstrate any benefit of aspirin in the long-term course of depression in this community-dwelling sample of older adults over a 5-year period, and identified an adverse effect of aspirin in the course of depression in those with pre-existing depressive symptoms.

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Fig. 1: Depressive symptoms recurrence/persistence.
Fig. 2: Sub-group analyses.

Data availability

The individual participant data that underlie the results reported in this article will be made available to others, after de-identification. Requests for data access will be via the ASPREE Principal Investigators with details for applications provided through the web site,, and in accord with the NIH policy on data sharing, details available at Data availability will commence on publication of this article. The supporting Protocol and Statistical Analysis Plan is already available as an independently published article. The supporting documents will be available at These data will be available to investigators whose proposed use of the data has been approved by a review committee in order to achieve the aims in the approved proposal. These data will be available through a web-based data portal safe haven, based at Monash University, Australia.


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Author contributions

Study design and grant application: MB, MM, JJM, RLW, RCS, PBF, ES, AMM, SD, MRN, JEL, RLW. Data collection: MB, RLW, MRN, RCS, CMR, ES, SMF, AMM, NS, JJM. Statistical analysis: MM, RLW, JEL. Manuscript preparation and editing. MB, BA, RLW, JEL, CM, SD, RLW, MRN, RCS, CMR, PBF, ES, SMF, AMM, NS, JJM.



This paper was supported by a grant (U01AG029824) from the National Institute on Aging and the National Cancer Institute at the National Institutes of Health, by grants (1081901, 334047 and 1127060) from the National Health and Medical Research Council of Australia. MB is supported by a NHMRC Senior Principal Research Fellowship (1059660 and 1156072).

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Correspondence to Michael Berk.

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Conflict of interest

MB has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Lundbeck, Merck, Pfizer, and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Lundbeck Merck, Pfizer and Servier—all unrelated to this work. PBF has received equipment for research from MagVenture A/S, Medtronic Ltd, Neuronetics and Brainsway Ltd and funding for research from Neuronetics. He is on scientific advisory boards for Bionomics Ltd and LivaNova and is a founder of TMS Clinics Australia: all unrelated to this work. MRN received travel and advisory board support from Bayer AG who provided product for the ASPREE study.

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Berk, M., Agustini, B., Woods, R.L. et al. Effects of aspirin on the long-term management of depression in older people: a double-blind randomised placebo-controlled trial. Mol Psychiatry 26, 5161–5170 (2021).

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