Depression, Statins and Cardiologists

by Duane Graveline, MD, MPH

Cardiologists know that treating depression will often benefit patients complaining of cardiovascular problems, but it's likely that they are completely unaware that statin drugs may be a major contributing factor.

According to a report from a National Heart, Lung and Blood Institute (NHLBI) Working Group, and published simultaneously in Annals of Behavioral Medicine and Psychosomatic Medicine, up to 20 percent of patients with heart disease meet the American Psychiatric Association's criteria for major depression, and identifying better treatments for depression in this population could lead to improved medical, financial and psychosocial outcomes.

At almost the same time, Goldstein and others of the Department of Physiology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel, report in Biol Psychiatry 60(5): 491-9 on the involvement of endogenous digitalis-like compounds in depressive disorders. Cholesterol is the major precursor of these endogenous digitalis-like compounds synthesized in our adrenals.

We might have predicted the effect of this new substance in something like heart failure because of the word digitalis, but who would have predicted its impact on bipolar disorder and other forms of depressive reactions?

These pleiotropic effects (more than one effect produced) are due to the cellular effects of statins on the sodium, potassium and ATPase cell wall channels in such a way as to induce calcium retention within the cells leading to altered response.

In a brain cell, mania can result from increased membrane excitability and depression from decreased transmitter release and these are only a few of the effects of these endogenous digitalis-like compounds synthesized from cholesterol.

What of the statin drugs with their ability to reduce natural cholesterol levels to values far below normal for the individual? Is there any real doubt that we now have another reason for the association of statin use with depression?

The drug industry proudly hails the ability of the stronger statins like atorvastatin, simvastatin, rosuvastatin and others to lower blood cholesterol some 40-50%.

We already know what this does to the cognitive ability of many people and the sexual function of many others. Now we find another major body system completely dependent upon adequate cholesterol levels.

In addition to this mechanism for altered emotional status we also have others and all are tied to cholesterol availability. The first of these is dolichol associated glycoprotein process for neurohormone synthesis. Every emotion and mood we have is governed by the makeup of sugars and protein fragments, linked like popcorn on a string, to make up our neurohormones.

The second involves our glial cell mediated production of "on-demand" cholesterol synthesis for memory synapses, critical to the development of psychological manifestations.

The third has to do with G-protein coupled receptors responsible for neurotransmitter coupling and felt to be the most important mechanism for perception of environmental factor cells.

All three of these are cholesterol dependent and therefore sensitive to statin use. The effects can be so subtle as to be hardly noticeable or so severe as to support the diagnosis of psychotic illness.

How could the designers of lucrative statin drugs over two decades ago know of these effects? They obviously could not and now after 25 years of use, have some very real economic reasons for not wanting to hear this.

One might say that the research community is now documenting adverse reactions to statin drug use that should have been defined and warned of long before marketing.

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

Updated July 2016

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