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The effect of concomitant treatment with selective serotonin reuptake inhibitors and statins: A population-based study

Small clinical trials have indicated that statins improve antidepressant treatment effects. We performed a register-based study including 872,216 individuals who initiated treatment with selective serotonin reuptake inhibitors (SSRIs). Individuals using SSRIs+statins were associated with a lower risk for hospitalization with depression, as compared to SSRIs alone, suggesting that concomitant treatment with SSRIs and statins may have better antidepressant treatment effects.

Ole Köhler, MD, PhD student at Psychosis Research Unit, Aarhus University Hospital, Risskov

About the study

Small clinical trials have indicated that the cholesterol-lowering drugs statins may improve the antidepressant treatment effects of selective serotonin reuptake inhibitors (SSRIs). This effect may be mediated by the anti-inflammatory properties of statins.

By applying the Danish nationwide registers, we sought to investigate whether the combination of SSRIs+statins had superior antidepressant effects compared to SSRIs alone. We included 872,216 individuals, who began SSRI treatment between 1997-2012. Of these, a total of 113,108 (13.0%) used statins concomitantly. We compared risk time on SSRI+statins versus risk time on SSRIs only.

When compared to SSRI use only, we found that the combination of SSRIs+statins was associated with a lower risk for any psychiatric hospitalization (hazard rate ratio=0.75; 95%-CI=0.69; 0.82) and with a lower risk for hospitalization with depression (hazard rate ratio=0.64; 95%-CI=0.55; 0.75). These effects were also significant for the most frequently used SSRI+statin combination, namely citalopram+simvastatin.

Importantly, the combination of SSRI+statins had no significant negative effects on all-cause mortality (hazard rate ratio=1.04; 95%-CI=0.96; 1.12) or suicidal behaviour (hazard rate ratio=0.85; 95%-CI=0.61; 1.18).

All of the analyses were adjusted for several potential confounders. Furthermore, the abovementioned results were supported by propensity-score matched analyses. We were able to propensity-score match 22,478 individuals using SSRIs+statins in a 1:1 matching fashion with 22,478 individuals using SSRIs only.

Hence, our results indicate that the combination of SSRIs+statins may have better antidepressant effects compared to SSRIs alone. Ideally, SSRI+statin combinations (for instance citalopram+simvastatin) should be tested against SSRI monotherapy (citalopram) in large randomized clinical trials in the future.

The paper “ The effect of Concomitant Treatment With SSRIs and Statins: A Population-Based Study” was published in the American Journal of Psychiatry, 2016 May 3 [Epub ahead of print]

Facts about the study

  • Register-based study including 872,216 individuals; 759,108 using SSRIs only, and 113,108 individuals using SSRIs and statins.
  • SSRIs+statins were associated with a lower risk of hospitalization due to depression and any psychiatric hospitalization.
  • We performed sub-analyses on a propensity-score matched study population, yielding similar results.
  • Clinical trials need to further investigate whether SSRIs+statins have better antidepressant effects compared to SSRIs alone.

Further information:

Ole Köhler, MD, PhD student at Psychosis Research Unit, Aarhus University Hospital, Risskov

E-mail: karkoe@rm.dk.