The Use of Statins After a Cardiac Intervention Is Associated With Reduced Risk of Subsequent Depression: Proof of Concept for the Inflammatory and Oxidative Hypotheses of Depression?

Objective: Depression is associated with immune activation as well as oxidative stress. Statins have in vitro and in vivo antiinflammatory and antioxidative properties. We prospectively investigated whether the use of statins was associated with a reduced risk of development of depression in individuals who have had a cardiac event or intervention.

Method: Participants were recruited between May 2005 and March 2006 from the Geelong Hospital, Geelong, Australia, a tertiary hospital in regional Australia that serves a catchment area shown to be representative of the broader Australian community. Patients who were hospitalized for angioplasty, myocardial infarction, or coronary artery bypass graft surgery (N = 193) were followed up prospectively for 9 months to assess development of depression. Depression data were collected 3 months postdischarge (T1) by structured clinical interview (using the Mini International Neuropsychiatric Interview, version 5) and 9 months postdischarge (T2) by self-report (using the Hospital Anxiety and Depression Scale). Major depressive disorder, minor depression, and dysthymia were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Data on statins were collected from medical records. The association between statin therapy and depression was tested using both linear and logistic regression models controlling for clinical, psychological, and demographic confounders.

Results: At discharge, 157 participants (81.3%) were receiving statin therapy. Adjusting for possible confounders, taking statins at discharge had a protective effect on depression at T1, reducing the likelihood of dysthymia, minor depression, or major depression by 69% (95% CI, 0.097-0.972; P = .045). At the T2 end point, statin therapy again had a protective effect and was associated with a 79% reduction in the likelihood of depression (95% CI, 0.052-0.876; P = .032). The linear regression model to predict depression at T2 was significantly different from zero (F11,180 = 8.686, P < .001) and explained 36.3% of the variance in depression.

Conclusions: The use of statins was associated with significant reduction in the risk of depression in individuals who have had a cardiac event. This supports the role of oxidative and inflammatory processes in depression and opens the door to rational and novel pathophysiologically based therapies distinct from conventional antidepressants.

J Clin Psychiatry

Submitted: November 9, 2009; accepted March 15, 2010.

Online ahead of print: December 14, 2010 (doi:10.4088/JCP.09m05825blu).

Corresponding author: Michael Berk, MD, PhD, Department of Clinical and Biomedical Sciences, Barwon Health, University of Melbourne, PO Box 281, Geelong VIC 3220, Australia (mikebe@barwonhealth.org.au).