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Issue Links: Learning Objectives

Topics: Depression | Research Update

Review of: Köhler O, Gasse C, Petersen L, et al. The effect of concomitant treatment with SSRIs and statins: a population-based study. American Journal of Psychiatry 2016;173(8):807–815.

Study Type: Naturalistic cohort study

Is depression a disorder of inflammation? This intriguing hypothesis has been floating around in the literature over the past few years. Thus far, the findings are suggestive but not definitive. For instance, one marker of inflammation, C-reactive protein, was found to be higher in people with psychological distress and depression (Wium-Andersen MK et al, JAMA Psychiatry 2013;70:176–184). In addition, small clinical trials have shown that adding anti-inflammatory medications (such as celecoxib and the statin lovastatin) to antidepressants is more effective than adding placebo. But we need more data before we start routinely prescribing these meds to our depressed patients.

While statins are used primarily to lower cholesterol, they also have direct anti-inflammatory effects. In order to explore whether statins might augment the effects of SSRIs, researchers from Denmark mined data from the Danish National Prescription Registry, a national database that collects information on all prescription medications picked up at pharmacies across the country. Between 1997 and 2012, a total of 872,216 patients started SSRIs, of whom 113,108 (13%) also took a statin drug at the same time. The two groups were compared on the following outcomes: rate of psychiatric hospital contacts (any reason), psychiatric hospital contacts related to depression, suicidality, and overall mortality.

Results

Compared to SSRIs alone, those in the combined SSRI and statin group were 36% less likely to present to a psychiatric hospital specifically for depression. They were also 25% less likely to show up at a psychiatric hospital for any reason. Statin users had no increased risk of suicidality, an important finding given that earlier data suggested a connection between lowered cholesterol and suicide risk.

TCPR’s Take

This is a strong study because it analyzed data from literally all people in Denmark who had been on an SSRI over a 15-year period. Therefore, we can be certain that any findings from this sample are absolutely generalizable to the Danish population as a whole. However, since it is an observational study, it’s not clear that statin use actually caused less depression; there may be other factors responsible. For example, patients who received statins may have made healthy lifestyle changes to combat high cholesterol, such as exercising more. We know that exercise is good for mood, so this could be one confounding factor among others. The authors statistically controlled for many confounders, but they did not control for diet or exercise.

Practice implications

The study is intriguing, but it’s probably too soon to start augmenting SSRIs with statins as a treatment for depression. We need more clinical trial data. On the other hand, you might want to share the results of this study with your patients who are considering going on statins for hyperlipidemia but are ambivalent. These data are a check mark in the ­positive column.