The Effect of Concomitant Treatment With SSRIs and Statins: A Population-Based Study

Am J Psychiatry. 2016 Aug 1;173(8):807-15. doi: 10.1176/appi.ajp.2016.15040463. Epub 2016 May 3.


Objective: Both preclinical studies and clinical trials have indicated that the combination of a selective serotonin reuptake inhibitor (SSRI) and a statin may have superior antidepressant effects compared with SSRI treatment alone. The authors sought to assess whether this beneficial effect can be generalized to a more heterogeneous population of SSRI users.

Method: In a nationwide cohort study that included all incident SSRI users in Denmark between 1997 and 2012, the authors compared people who had periods of concomitant use of SSRIs and statins with people who had periods of SSRI treatment alone. Outcomes included the rates of psychiatric hospital contacts (any cause), psychiatric hospital contacts due to depression, suicidal behavior, and all-cause mortality. Using Cox regression and competing risk analysis, the authors calculated crude and adjusted hazard ratios for these outcomes.

Results: The authors identified 872,216 incident SSRI users, of whom 113,108 (13.0%) used a statin concomitantly. Compared with SSRI treatment alone, the combined use of an SSRI and a statin was associated with a significantly lower risk for both psychiatric hospital contacts (adjusted hazard ratio=0.75 (95% CI=0.69, 0.82) and psychiatric hospital contacts due to depression (adjusted hazard ratio=0.64, 95% CI=0.55, 0.75). Compared with SSRI treatment alone, the concomitant use of SSRIs and statins was not associated with significant increases in all-cause mortality (adjusted hazard ratio=1.04, 95% CI=0.96, 1.12) or suicidal behavior (adjusted hazard ratio=0.85, 95% CI=0.61, 1.18).

Conclusions: In a large naturalistic cohort, concomitant treatment with SSRIs and statins resulted in robust advantages compared with SSRIs alone.

MeSH terms

  • Cohort Studies
  • Denmark
  • Depressive Disorder / drug therapy*
  • Drug Synergism
  • Drug Therapy, Combination
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Patient Admission / statistics & numerical data
  • Population Surveillance
  • Proportional Hazards Models
  • Risk
  • Serotonin Uptake Inhibitors / therapeutic use*


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Serotonin Uptake Inhibitors