Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Is Statin Treatment Linked with Depression Risk?

J Affect Disord; 2019 Mar; Köhler-Forsberg, et al

The association between statin treatment and antidepressant use is unspecific (equivalent association between statins and most other drugs), according to a recent study. Furthermore, the association between statin use and depression diagnoses is mediated by residual confounding, bias, or by downstream effects of the statin prescription (seeing a physician more often). Researchers identified all statin users in the period from 1996 to 2013 among individuals in a national database born between 1920 and 1983. 1 non-user was matched to each statin user based on age, sex and a propensity score taking several potential confounders into account. They found:

  • A total of 193,977 statin users and 193,977 non-users were followed for 2,621,282 person-years.
  • Statin use was associated with 1) increased risk of antidepressant use (hazard rate ratio [HRR]=1.33), 2) increased risk of any other prescription drug use (HRR=1.33), 3) increased risk of receiving a depression diagnosis (HRR=1.22)—but not after adjusting for antidepressant use (HRR=1.07), 4) reduced cardiovascular mortality (HRR=0.92), and 5) reduced all-cause mortality (HRR = 0.90).

Köhler-Forsberg O, Gasse C, Petersen L, Nierenberg AA, Mors O, Østergaard SD. Statin treatment and the risk of depression. J Affect Disord. 2019;246(1):706-715. doi:10.1016/j.jad.2018.12.110.


This study reinforces smaller studies, which demonstrate that antidepressants for depression, when combined with a statin for hyperlipidemia, conveyed additive antidepressant effects. Using a large-scale population approach, researchers found that after starting a statin, there was an increased chance that the hyperlipidemic patient would later be prescribed an antidepressant. Theoretically, being placed on a statin increases a patient’s medical utilization and clinical visits that, in turn, may drive up a wide array of prescribing and assignment of other diagnoses, such as major depressive disorder (MDD). Ultimately, despite some initial evidence that statins may improve depression, there appears to be no cumulative benefit. This study, however, indicates that clinicians should continue to look for novel treatment strategies for one of the most disabling conditions worldwide.—Thomas L. Schwartz, MD; Senior Associate Dean of Education, Interim Chair/Professor of Psychiatry, SUNY Upstate Medical University.