Effects of Statins Against Depression

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EFFECTS OF STATINS AGAINST DEPRESSION

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Effects of statins against depression Keywords: statins, depression, pharmacy, mechanism

ABBREVIATIONS MDD = Major Depressive Disorder; NSAIDs = nonsteroidal anti-inflammatory drugs; LDL = lowdensity

Introduction Major depressive disorder (MDD) is a serious and often recurrent mental disorder with aprevalence and a lifetime incidence of up to 20% in which it has a high comorbiditywith medical

conditions.

Several

been

studied

lithium,

some and

are

currently

thyroid

used

CRP = C-reactive protein; LFA-1

However,The evidence base for the efficacy of these drug combinations is limited. In

pituitary-adrenal; RCT =

antipsychotics,

and

asantidepressants.

antigen-1; HPA = hypothalamo-

includes

have

lipoprotein; IL = Interleukin;

= leukocyte function

This

drugs

hormones.

addition, theyare often associated with significant side effects, including weight gain, tremor,

nausea,sedation,

and

sometimes

cause

effects

on

the

cardiometabolic

Randomized Clinical Trial;

system.However, statins are generally effective and safer any adverse effects that may

NMDA = Nmethyl-D-aspartate;

occur,even possessing the benefit of lowering cholesterol, an effect that is likely to be

BDNF = brain-derived

beneficialfor a substantial fraction of patients. It is worth mentioning that statins have

neurotrophic factor; HDRS = Hamilton Depression Rating Scale; SSRI = Selective Serotonin Reuptake Inhibitor;

pleiotropiceffects on several (neuro) biological systems that are believed to be involved in theetiopathogenesis synapticplasticity,

of

depression,

oxidative

stress

including and

putative

excitotoxicity

effects in

the

on

neurotransmission,

central

protectiveeffects on the cardiovascular and immunomodulatory effects.

nervous

system,

Mechanism The antidepressant mechanisms of statins could also be related to their effects on atherosclerosis. The presence of lesions in the white matter in the cerebral arteries represents the hallmark of the vascular system. According to the analysis statins can prevent depression, particularly in older people. If statins prevent cerebrovascular changes they can prevent the development of depression. It is worth mentioning that in meta-analysis studies it is suggested that there is an antidepressant effect due to the blockade of the NMDA receptor in patients with depression. Furthermore, statins increase brain- derived neurotrophic factor (BDNF) in the hippocampus and meta-analysis studies have shown that low BDNF is a marker of MDD in humans and that BDNF levels increase with successful treatment. Finally, statins positively regulate the expression of dopamine D1 and D2 receptors in the rat prefrontal cortex, and alterations in D1 and D2 receptors have been associated with the etiology of MDD. In summary, there are several plausible neurobiological effects of statins on inflammation, glucocorticoids, serotonin, NMDA receptors, BDNF, and dopamine receptors that potentially contribute to their antidepressant effects. Many of the proposed "antidepressant" mechanisms of statins, especially those that affect the CNS (eg, neurotransmission, plasticity, and others), are difficult or impossible to study in vivo in humans. Therefore, it will be difficult to

discern

which

of

the

pleiotropic

effects

exerted

by

statins

are

essential

or

necessary

for

an

"antidepressant" effect in humans.

Figure 1: Potential mechanisms explaining antidepressant effects of statins.

With current evidence, it cannot be firmly concluded or refuted that statins have antidepressant effects. Currently, the most promising findings are statins combined with SSRIs in patients with overt MDD. In future studies, it will be very informative to include biomarkers to help understand the mechanisms by which statins could exert their potential antidepressant effect.

All credits of scientific information are for the authors of the scientific article creation!

Scientific information reference: Köhler-Forsberg, O., Otte, C., Gold, S. M., & Østergaard, S. D. (2020). Statins in the treatment of depression: Hype or hope?

Pharmacology & Therapeutics, 107625. doi:10.1016/j.pharmthera.2020.107625

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