Michael Berk1,2,3,4, Robyn L Woods2, Mark R Nelson5, Raj C Shah6, Christopher M Reid2,7, Elsdon Storey2, Sharyn Fitzgerald2, Jessica E Lockery2, Rory Wolfe2, Mohammadreza Mohebbi1,8, Seetal Dodd1, Anne M Murray9, Nigel Stocks10, Paul B Fitzgerald11,12, Catherine Mazza1, Bruno Agustini1, John J McNeil2. 1. The Institute for Mental and Physical Health and Clinical Translation Strategy Research Centre, Deakin University School of Medicine, Geelong, Australia. 2. School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. 3. Department of Psychiatry, University of Melbourne, Parkville, Australia. 4. Orygen Youth Health Research Centre, Parkville, Australia. 5. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia. 6. Rush Alzheimer's Disease Center, Department of Family Medicine, Rush University Medical Center, Chicago, Illinois. 7. School of Public Health, Curtin University, Perth, Australia. 8. Biostatistics Unit, Faculty of Health, Deakin University, Geelong, Australia. 9. Berman Center for Outcomes and Clinical Research, Hennepin Healthcare Research Institute, Minneapolis, Minnesota. 10. Discipline of General Practice, Adelaide Medical School, University of Adelaide, Australia. 11. Epworth Centre for Innovation in Mental Health, the Epworth Clinic, Epworth Healthcare, Camberwell, Australia. 12. Monash Alfred Psychiatry Research Centre, Central Clinical School, Monash University, Melbourne, Australia.
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 receivedaspirin 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.
RCT Entities:
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.
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