Effect of Aspirin vs Placebo on the Prevention of Depression in Older People: A Randomized Clinical Trial

Abstract

Importance: Depression is associated with increased inflammation, which may precede its onset, especially in older people. Some preclinical data suggest potential antidepressant effects of aspirin, supported by limited observational data suggesting lower rates of depression in individuals treated with aspirin. There currently appears to be no evidence-based pharmacotherapies for the primary prevention of depression.

Objective: To determine whether low-dose aspirin (100 mg) reduces the risk of depression in healthy older adults.

Design, setting, and participants: This double-blinded, placebo-controlled randomized clinical trial was a substudy of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which examined if aspirin increased healthy life span, defined as survival free of dementia and disability. The prespecified secondary outcome was depression. Individuals of all races/ethnicities older than 70 years in Australia, as well as white individuals older than 70 years and black and Hispanic individuals older than 65 years in the United States, were included.

Interventions: Participants were randomized to aspirin (100 mg daily) or placebo, with a median (interquartile range) follow-up of 4.7 (3.5-5.6) years.

Main outcomes and measures: The primary outcome was a proxy measure of major depressive disorder defined as a score of 8 or more on the Center for Epidemiologic Studies Depression 10-item (CES-D-10) scale.

Results: Of the 19 114 participants enrolled in the trial, 9525 received aspirin and 9589 received a placebo. The mean (SD) age was 75.2 (4.0) years in the aspirin group and 75.1 (4.5) years in the placebo group; 9531 (56.4%) were women. Participants' demographics and clinical characteristics at baseline were similar between groups. A total of 79 886 annual CES-D-10 measurements were taken, with a mean of 4.2 measurements per participant. There were no significant differences at annual visits in the proportions of CES-D-10 scores of 8 or more between the aspirin and placebo groups. The incidence rate of new CES-D-10 scores of 8 or more was 70.4 events per 1000 person-years in the aspirin group and 69.1 in the placebo group (hazard ratio, 1.02 [95% CI, 0.96-1.08]; P = .54).

Conclusions and relevance: Low-dose aspirin did not prevent depression in this large-scale study of otherwise healthy older adults.

Trial registration: ClinicalTrials.gov Identifier: NCT01038583.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Berk has received grant/research support from the National Institutes of Health, 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, as well as a National Health and Medical Research Council senior principal research fellowship during the conduct of the study; has been a speaker for AstraZeneca, Lundbeck, Merck, and Pfizer; has served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Lundbeck Merck, Pfizer and Servier; has received personal fees from Grunbiotics, Livanova, Norwegian Psychiatry Association, Janssen Cilag, Otsuka, Medisquire, HealthEd, Medplan Communications, and Royal Australian and New Zealand College of Psychiatrists outside the submitted work; and has a patent to modulation of physiological processes and agents useful for the same pending, a patent to modulation of diseases of the central nervous system and related disorders pending, and a patent to xanthone-rich plant extracts or compounds therefrom for modulating diseases of the central nervous system and related disorders, issued. Dr Shah receives research support from Eli Lilly and Co Inc, Genentech Inc, Merck and Co Inc, H. Lundbeck A/S, Navidea Biopharmaceuticals, Takeda Development Center Americas Inc, and Toyama Chemical Co, Ltd, as a site principal investigator or a site subinvestigator. Dr Nelson has participated in trials that have received funding from SmithKline Beecham, AstraZeneca, Bayer, Sanofi-Aventis, Merck Sharp & Dohme, Pfizer, Servier Laboratories, and Bristol-Myers Squibb; has served on advisory boards for Sanofi-Aventis, Novartis, Schering-Plough Solvay Pharmaceuticals, and Amgen; has prepared educational material for Servier Laboratories, AstraZeneca, Bristol-Myers Squibb, and MediMark; and has received conference and travel support from Bayer HealthCare AG, Merck Sharpe and Dohme, Novartis, and Sanofi-Aventis. Dr Fitzgerald is supported by a National Health and Medical Research Council practitioner fellowship (1078567); has received equipment for research from MagVenture A/S, Medtronic Ltd, Neuronetics, and Brainsway Ltd, and funding for research from Neuronetics; is on scientific advisory boards for Bionomics Ltd and LivaNova; and is a founder of TMS Clinics Australia. Dr Woods reported grants from the National Institutes of Health, National Health and Medical Research Council, and Victorian Cancer Agency and nonfinancial support from Monash University during the conduct of the study. Dr Nelson reported personal fees from Bayer Healthcare outside the submitted work. Dr Shah reported grants from National Institutes of Health during the conduct of the study. Dr Reid reported grants from National Health and Medical Research Council and the National Institute on Aging during the conduct of the study. Dr Storey reported grants from the National Institutes of Health and National Health and Medical Research Council during the conduct of the study. Dr Wolfe reported grants from the National Institutes on Aging and National Health and Medical Research Council during the conduct of the study. Dr Dodd reported grants from Harry Windsor Foundation and grants from National Health and Medical Research Council outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Consolidated Standards of Reporting Trials Diagram for the Aspirin for the Prevention of Depression Trial

CES-D-10 indicates Center for Epidemiologic Studies Depression 10-item scale.

Figure 2.. Cumulative Incidence of Incident Depression

An episode of major depressive disorder was defined as Center for Epidemiologic Studies Depression 10-item scale score of 8 or more. Shown is the cumulative incidence of incident depression (ie, first episodes of depression among those in whom it was not present at baseline) observed during the trial.