Do Statins have antidepressant effects?

Evidence supporting  inflammatory etiology of depression is gaining strength. Inflammation is considered as an operative pathway that links physical disorders with depression. The role of statins in depressive disorders is an interesting one in this context. Statins have become the best selling medication in the history  and hence it is important to know their effects on mood disorders.

Statins inhibit the enzyme HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis in the liver. CVD preventive effects of statin is seen more in those with raised CRP levels to the extent that some authors suggest that CRP is a better marker of CVD preventive effects of statins. Various observations like this suggest that statins have anti-inflammatory properties.

Statins as antidepressant augmenting agents 

In the last 4 years, attempts have been made to see the antidepressant effect of statins. (examples: Ghanizadeh 2013, Haghighi 2014, Gougol 2015 ). All these studies show that adding statin to SSRI augments the antidepressant response significantly. A meta analysis by Salagre et al 2016 confirms these findings. (standard mean difference (SMD) of -0.73; 95% CI -1.04 to -0.42; p \ 0.001)

Statins prevent depressive relapses?

The above experimental findings are supported by epidemiological observations as well. A notable study is the Danish one ( Kohler et al 2016) with 800,000 plus patients showing  that combined treatment with an SSRI and a statin was associated with a 36% decreased risk for hospitalization with depression (hazard rate ratio of 0.64; 95% CI 0.55–0.75) compared with treatment with an SSRI only.

Do statins have primary preventive effects?

Meta analysis of seven observational studies found that statin users were 32% less likely to develop depression compared with non-users (Parsaik et al 2014). Another meta analysis showed that those on statins are better in their mood states. (O’Neil et al 2012). But all observations studies are limited by confounders.

Is there risk of depression if LDL levels are too low?

Among elderly , there is some evidence to suggest that statin may cause cognitive decline and depressive symptoms. An inverse relationship  between LDL cholesterol and depression is suggested ( Mandas et al 2014). Previous reports of suicidal ideation and low cholesterol has been contested in later studies. However, it might still be that, severe depletion of cholesterol may have effects on membrane lipids that are crucial in syntactic signalling.

Class effect ?

It appears that statins observed effects in depression is a class property. However, some epidemiological studies show some difference between agents as well. It might be linked to their ability to cross BBB (for example, atorvastatin crossing easily than others).  The subgroup with higher CRP levels may respond better to combination of statin and SSRI. There is some suggestion that if CRP is elevated, tricyclics might be even more effective. However, this has not been studied yet.

Conclusion

Studies suggest that statin have anti-inflammatory property independent of  lipid lowering effect. This may explain the anti depressant like effect seen when added to SSRI. Factors like inflammatory markers, genetics, type of depression, Cvd comorbidity may impart differential effects. In general, evidence suggest that statins can be helpful in depression.

 

Further reading:

 

Do Statins Have Antidepressant Effects? Köhler-Forsberg O, Gasse C, Berk M, Østergaard SD.CNS Drugs. 2017 May;31(5):335-343

Interactions between pro-inflammatory cytokines and statins on depression in patients with acute coronary syndrome.Kim SW, Kang HJ, Bae KY, Shin IS, Hong YJ, Ahn YK, Jeong MH, Berk M, Yoon JS, Kim JM.Prog Neuropsychopharmacol Biol Psychiatry. 2017 Jul 6

Statins for the treatment of depression: A meta-analysis of randomized, double-blind, placebo-controlled trials.Salagre E, Fernandes BS, Dodd S, Brownstein DJ, Berk M.J Affect Disord. 2016 Aug;200:235-42. doi: 10.1016/j.jad.2016.04.04

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