Review Statins use and risk of depression: A systematic review and meta-analysis Ajay K. Parsaik a,b , Balwinder Singh b , M. Hassan Murad c,d , Kuljit Singh e , Soniya S. Mascarenhas f , Mark D. Williams g , Maria I. Lapid g , Jarrett W. Richardson g , Colin P. West h,i , Teresa A. Rummans g,j,n a Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, United States b Mayo Alzheimer's Disease Research Center, Mayo Clinic, Rochester, MN, United States c Knowledge and Evaluation Research, Mayo Clinic, Rochester, MN, United States d Division of Preventive Medicine, Mayo Clinic, Rochester, MN, United States e Department of Cardiology, Queen Elizabeth Hospital, Woodville South, SA, Australia f Health Care Management, London Training College, London, UK g Department of Psychiatry, Mayo Clinic, Rochester, MN, United States h Division of General Internal Medicine, Mayo Clinic, Rochester, MN, United States i Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States j Department of Psychiatry, Mayo Clinic, Jacksonville, FL, United States article info Article history: Received 20 August 2013 Received in revised form 17 October 2013 Accepted 30 November 2013 Available online 17 December 2013 Keywords: Statins Depression Systematic review Meta-analysis abstract Importance: Statin use has been associated with depression; however studies of the association between statin use and depression have yielded mixed results. Objective: To determine whether statin use is associated with depression and to evaluate the evidence supporting this association. Data sources: Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched through December 28, 2012. Study selection: We included studies that evaluated exposure to statins, reported the development of depression, and relative risks or odds ratios (ORs) or provided data for their estimation. Two reviewers screened 981 abstracts independently using a standardized form, reviewed full text of 59 selected articles, and included 7 studies in this metaanalysis. Data extraction and synthesis: Study design, statin exposure, development of depression, and study quality were extracted by 2 independent reviewers. A pooled OR with 95% confidence interval (CI) was estimated using the random-effects model and heterogeneity was assessed using Cochran's Q test and the I 2 statistic. Results: Seven observational studies (4 cohort, 2 nested case-control, and 1 cross-sectional) from 5 countries enrolling 9187 patients were included. Statin users were 32% less likely to develop depression than nonusers (adjusted OR, 0.68; 95% CI, 0.52–0.89). Modest heterogeneity was observed between the studies (I 2 ¼55%, P ¼0.01), which could be accounted for by one study, exclusion of which removed the heterogeneity (P ¼0.40, I 2 ¼2%) and further strengthened the antidepressant effect of statin (adjusted OR, 0.63; 95% CI, 0.43–0.93). Heterogeneity could not be explained by study design or study population. The quality of supporting evidence was fair. Conclusions and relevance: This systematic review and meta-analysis suggests that statin use is associated with lower risk for depression. However, higher-quality studies are needed to confirm the magnitude of this association. & 2013 Elsevier B.V. All rights reserved. Contents 1. Introduction ......................................................................................................... 63 2. Methods ............................................................................................................ 63 2.1. Study eligibility ................................................................................................ 63 Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/jad Journal of Affective Disorders 0165-0327/$ - see front matter & 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jad.2013.11.026 n Correspondence to: Department of Psychiatry, Mayo Clinic, 200 1st Street, SW, Rochester, MN, United States. Tel.: þ1 507 284 2511; fax: þ1 507 538 0878. E-mail address: rummans.teresa@mayo.edu (T.A. Rummans). Journal of Affective Disorders 160 (2014) 62–67