[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 35.173.48.53. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Views 9,504
Citations 0
Original Investigation
June 3, 2020

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

Author Affiliations
  • 1The Institute for Mental and Physical Health and Clinical Translation Strategy Research Centre, Deakin University School of Medicine, Geelong, Australia
  • 2School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
  • 3Department of Psychiatry, University of Melbourne, Parkville, Australia
  • 4Orygen Youth Health Research Centre, Parkville, Australia
  • 5Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
  • 6Rush Alzheimer’s Disease Center, Department of Family Medicine, Rush University Medical Center, Chicago, Illinois
  • 7School of Public Health, Curtin University, Perth, Australia
  • 8Biostatistics Unit, Faculty of Health, Deakin University, Geelong, Australia
  • 9Berman Center for Outcomes and Clinical Research, Hennepin Healthcare Research Institute, Minneapolis, Minnesota
  • 10Discipline of General Practice, Adelaide Medical School, University of Adelaide, Australia
  • 11Epworth Centre for Innovation in Mental Health, the Epworth Clinic, Epworth Healthcare, Camberwell, Australia
  • 12Monash Alfred Psychiatry Research Centre, Central Clinical School, Monash University, Melbourne, Australia
JAMA Psychiatry. Published online June 3, 2020. doi:10.1001/jamapsychiatry.2020.1214
Key Points

Question  Does low-dose aspirin reduce the risk of depression in healthy older adults?

Findings  In this randomized clinical trial of 19 114 older adults in Australia and the United States, those taking low-dose aspirin (100 mg daily) did not have a lower rate of prevalent depression compared with those taking a placebo, per measurements taken at any of the postrandomization annual visits.

Meaning  In this study, low-dose aspirin did not prevent depression in healthy older adults.

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

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    3 Comments for this article
    EXPAND ALL
    Clarification of statement in this article's abstract
    Jack Modell, MD | Contract research organization
    The authors note, "There currently appears to be no evidence-based pharmacotherapies for the primary prevention of depression." While this statement is true with regard to prevention of depression in the general population, which indeed may be what is intended by "primary prevention," bupropion extended-release (Wellbutrin XL) was approved in 2006 for the prevention of seasonal depressive episodes in [non-depressed] patients with a diagnosis of seasonal affective disorder (https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021515s036lbl.pdf). To my knowledge (please correct me if I am mistaken), this is currently the only approved pharmacotherapy for prevention of depressive episodes prior to their onset.
    CONFLICT OF INTEREST: None Reported
    Lack of pharmacokinetic basis for research.
    Iouri Banakh, MClinPharm | Peninsula Health, Frankston Hospital
    Low dose aspirin has antiplatelet effects, but not anti-inflammatory effects due to the first pass effect by the liver. The results of this study were completely predictable and of little scientific value. A larger dose that gets through to the main circulation would have actually answered the question if aspirin provides a benefit in reducing depression. It is disappointing to see such research published when basic pharmacokinetics of the drug have not been considered or mentioned in the methods or background.
    CONFLICT OF INTEREST: None Reported
    RE: Effect of aspirin vs placebo on the prevention of depression in older people
    Tomoyuki Kawada, MD | Nippon Medical School
    Berk et al. conducted a double-blinded, placebo-controlled randomized clinical trial to evaluate the relationship between low-dose aspirin (100 mg) and risk (benefit) of depression in healthy older adults. The authors defined major depressive disorder as a score of 8 or more on the Center for Epidemiologic Studies Depression 10-item (CES-D-10) scale. There were no significant differences in the proportions of CES-D-10 scores of 8 or more between the aspirin and placebo groups. Namely, hazard ratio (95% confidence interval [CI]) of aspirin use for depression was 1.02 (0.96-1.08), and low-dose aspirin did not prevent depression in healthy older adults. I have some concerns about their study.

    Fundamentally, CES-D-10 scale is not a tool for making diagnosis of major depression. Instead, it reflects depressive symptoms caused by several intrinsic and extrinsic factors. This is not related to the cut-off point, and there is a gap between structured interview and CES-D-10 scale score.

    First, I suspect that the authors speculated the mechanism of the association between aspirin use and (the risk reduction of) depression via prevention of (micro-) infarct and/or early-stage of neuro-degeneration. As many actors are related to depression/depressive symptom, the lack of association cannot be confirmed in this trial. Anyway, structured interview seems to be indispensable to verify the association.

    Second, Kim et al. conducted a meta-analysis to evaluate the association between aspirin use and depression. Pooled odds ratio/relative risk (RR) (95% CI) of aspirin use for depression was 1.10 (1.05-1.16) without heterogeneity. In cases of prospective studies, pooled RR (95% CI) of aspirin use for depression was 1.11 (1.08-1.14). Furthermore, a duration of aspirin use ≥5 years and a dosage ≥500 mg daily was significantly associated with depression. In this review, aspirin use had an adverse effect on depression, and there is no benefit of aspirin use for depression incidence. I recommended to conduct a meta-analysis of a randomized clinical trials to verify the association.


    References
    1. Berk M, Woods RL, Nelson MR, et al. Effect of aspirin vs placebo on the prevention of depression in older people: A randomized clinical trial. JAMA Psychiatry. 2020 doi:10.1001/jamapsychiatry.2020.1214
    2. Kim HB, Kim JS, Jung JG. The association between aspirin use and depression: a systematic review and meta-analysis of observational studies. Pharmacoepidemiol Drug Saf. 2020;29(6):613-622. doi:10.1002/pds.5011
    CONFLICT OF INTEREST: None Reported
    READ MORE
    ×