CNS Drugs

, Volume 33, Issue 7, pp 685–694 | Cite as

Association Between Statin Use and Depressive Symptoms in a Large Community-Dwelling Older Population Living in Australia and the USA: A Cross-Sectional Study

  • Bruno AgustiniEmail author
  • Mohammadreza Mohebbi
  • Robyn L. Woods
  • John J. McNeil
  • Mark R. Nelson
  • Raj C. Shah
  • Anne M. Murray
  • Michael E. Ernst
  • Christopher M. Reid
  • Andrew Tonkin
  • Jessica E. Lockery
  • Michael Berk
  • the ASPREE Investigator Group
Original Research Article



Statin use has been frequently associated with depressive symptoms in an older population. However, the nature of this association is uncertain in the literature. In this study, we aimed to investigate the association of statin intake and the prevalence of depressive symptoms in healthy community-dwelling older adults living in Australia and the USA.


We analysed baseline data from 19,114 participants, over 70 years of age (over 65 years of age, if from an ethnic minority). The association of self-reported statin use and prevalence of depressive symptoms, as measured by a validated depression scale [Center for Epidemiological Studies Depression Scale (CES-D 10)], was determined using logistic regression models. Multivariable logistic models were implemented to account for important demographics and other lifestyle and socioeconomic factors, such as sex, age, living status, education and smoking history.


A total of 5987 individuals were statin users. Of those, 633 (10.6%) had depressive symptoms (CES-D 10 cut-off ≥ 8), compared with 1246 (9.5%) of the non-statin users. In the unadjusted model, statin use was associated with an increase in prevalence of depressive symptoms (odds ratio 1.13, confidence interval 1.02–1.25, p = 0.02). However, after adjusting for important demographic and socioeconomic factors, the use of statins was not significantly associated with depressive symptoms (odds ratio 1.09, confidence interval 0.98–1.20, p = 0.11). In secondary analyses, only simvastatin was marginally associated with an increased prevalence of depressive symptoms. Statins were associated with a decreased prevalence of depressive symptoms in individuals with severe obesity (body mass index > 35 kg/m2) and an increased prevalence in participants between 75 and 84 years of age.


This study in a large community-dwelling older population did not show any association of statins with late-life depressive symptoms, after accounting for important socioeconomic and demographic factors. Confounding by indication is an important issue to be addressed in future pharmacoepidemiologic studies of statins.



The authors acknowledge the efforts of research personnel and the long-term involvement of participants of the ASPREE study.

Author Contributions

JJM, RLW, MRN, RCS, CMR and JEL contributed to the design of the original ASPREE randomised controlled trial. MB, RLW, MRN, RCS, CMR, AT, CB, JEL, MM and JJM contributed to the design of the ASPREE-D sub-study. All authors actively participated in designing the current study. BA and MM performed the data analysis. BA drafted the manuscript that has been read, edited and approved by all co-authors.

Compliance with Ethical Standards


The study is supported by the National Institute on Aging and the National Cancer Institute at the National Institutes of Health (Grant No. U01AG029824), the National Health and Medical Research Council of Australia (Grant Nos. 334047, 1127060), Monash University (Australia) and the Victorian Cancer Agency (Australia). Michael Berk is supported by a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship (APP1059660 and APP1156072) and Christopher M. Reid is supported by a NHMRC Senior Research Fellowship (APP1045862).

Conflict of interest

Bruno Agustini, Mohammadreza Mohebbi, Robyn L. Woods, John J. McNeil, Mark R. Nelson, Raj C. Shah, Anne M. Murray, Michael E. Ernst, Christopher M. Reid, Andrew Tonkin, Jessica E. Lockery and Michael Berk have not conflicts of interest that are directly relevant to the content of this article.

Ethics approval

The ASPREE study was conducted in accordance with the Declaration of Helsinki 1964 as revised in 2008, the NHMRC Guidelines on Human Experimentation, the federal patient privacy (HIPAA) law and the International Conference of Harmonisation Guidelines for Good Clinical Practice. ASPREE also follows the Code of Federal Regulations as it relates to areas of clinical research.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Bruno Agustini
    • 1
    Email author
  • Mohammadreza Mohebbi
    • 1
    • 2
  • Robyn L. Woods
    • 3
  • John J. McNeil
    • 3
  • Mark R. Nelson
    • 4
  • Raj C. Shah
    • 5
  • Anne M. Murray
    • 6
  • Michael E. Ernst
    • 7
    • 8
  • Christopher M. Reid
    • 3
    • 9
  • Andrew Tonkin
    • 3
  • Jessica E. Lockery
    • 3
  • Michael Berk
    • 1
    • 10
  • the ASPREE Investigator Group
  1. 1.IMPACT Strategic Research Centre (Innovation in Mental and Physical Health and Clinical Treatment Strategic Research Centre), School of MedicineDeakin UniversityGeelongAustralia
  2. 2.Biostatistics UnitDeakin UniversityGeelongAustralia
  3. 3.School of Public Health and Preventive MedicineMonash UniversityMelbourneAustralia
  4. 4.Menzies Institute for Medical ResearchUniversity of TasmaniaHobartAustralia
  5. 5.Department of Family Medicine and Rush Alzheimer’s Disease CenterRush University Medical CenterChicagoUSA
  6. 6.Berman Center for Outcomes and Clinical ResearchHennepin Healthcare Research Institute, Hennepin HealthcareMinneapolisUSA
  7. 7.Department of Pharmacy Practice and Science, College of PharmacyThe University of IowaIowaUSA
  8. 8.Department of Family Medicine, Carver College of MedicineThe University of IowaIowaUSA
  9. 9.School of Public HealthCurtin UniversityPerthAustralia
  10. 10.Orygen, National Centre of Excellence in Youth Health, Department of Psychiatry and the Florey Institute for Neuroscience and Mental HealthUniversity of MelbourneMelbourneAustralia

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