Antidepressants - what do they really do?
Note - some of our blog posts will be somewhat scientifically advanced. This is one of them. We have a number of patients who attend the clinic who read widely and besides.... I just couldn't help myself, this is really exciting news in science....
Depression.
Truly, there wouldn't be anyone in the country (ok let's take the western world) who doesn't know someone who has it.
And yes,... depression is increasing in our society. Last year (2017), the Lancet published a study showing that the disability-adjusted life years (DALYs) brought on by depression had increased between 1990 and 2016 [1].
We've all been told that depression is an imbalance in chemicals (neurotransmitters) in the brain. This has been the rationale behind the use of medications classified as antidepressants.
I wouldn't be able to tell you the number of times that I have sat with patients, faithfully drawing out the following diagram to explain how their medication is thought to work. Prozac, one of the SSRIs (Selective Serotonin Re-uptake Inhibitors) and others in this group of medications are thought to work in the following way.
There you go... a slightly cropped photo of exactly what I would draw if you were in the office (corner missing as I had to hold down the crinkly page! )
The idea is that when a nerve signal is passed from one nerve to the next (at the synapse), the signal changes from an electrical impulse to a chemical message. Serotonin (in this case) which exists in packets called vesicules,... is released into the gap (synaptic cleft) between the nerves. This propogates a continuation of the electrical impulse down the next nerve. Simple right? The electrical impulse arrives at the end of the nerve. To jump the gap to the next nerve, the body uses a chemical message. So the electricity arrives and causes the vesicles floating around at the nerve ending to be pushed up to the membrane, to fuse and release their contents and viola! serotonin is released in the gap causing a nerve signal to be passed on to the next nerve.
And then we know that the body is smart, and once the message has been passed on, that serotonin in the gap is sucked back up into the cell that put it there and repackaged and reused.
If we assume that depression is caused by not enough firing of these "serotonergic" nerves (nerves using serotonin to jump the synaptic gap) how would we increase nerve firing? Well one way would be to stop the body from recycling the serotonin in the gap at the speed that it usually does. SSRI mediations like Prozac are thought to block receptors that suck up the Serotonin and repackage it to go through the process all over again. (Our bodies are wonderfully efficient and will recycle all sorts of things).
And this is what I have been drawing for patients. For years I have been telling them this is what is happening when they take Prozac and medicines like it (the SSRIs). I have been telling them this, because this is what we believed in medicine.
But is this really what is happening? Is this really the explanation as to exactly how SSRIs work {for some people's} depression?
You know one of the facts of life,... is that what we believe actually does more than just explain the obvious question in front of us. The under pinnings of our beliefs determine how we approach the world.
Well recent research tells us that Serotonin and the SSRIs may be working (again... for some) for other reasons.
It turns out we may not actually know a lot about what we are doing,.. or more accurately what we are effecting when we use SSRIs.
A review article [2] published 2 months ago points to the mounting research showing that the teaming trillions of bacteria called out "microbiome" - and specifically those living in our guts, is crucial to whether people get depressed or not. How crucial? As this article reviews, you can literally cause a human (or an animal) to become depressed it you give them the bacteria from a depressed persons/animals gut.
But guess what? It has been shown that the SSRIs alter the microbiome into a more favourable profile. And in fact that the serotonin signalling pathways in the above drawing I standardly create,... are quite slow to change.
So what happens if giving this medication is actually helping people to be less depressed through an entirely different mechanism... by at least in part, changing their gut bugs?
Anything else this medication could be doing? Well you wouldn't believe it, but the answer is yes. It turns out that Serotonin is involved in changing the regulation of how much or little, our genes are expressed. In other words, our "epi" (upon) genetics.
But what does that mean? Epigenetics is simply the other elements (not the genetic code itself) that determine whether a gene is expressed or not.
We are beginning to understand that much of what we see in the way of things that we think of as being "due to genes" is actually due to the changes in the epigenetic signalling. A number of studies now have been showing that SSRIs influence this epigenetic system. A study this last year in November[6] showed that Fluoxetine (Prozac) epigenetically increases the amount of something called BDNF - Brain Derived Neurotrophic Factor. BDNF is a wonderful chemical that is increased when we exercise and supports the brain. Conversely studies have shown that low levels of BDNF are correlated with depression. So only in the past few years have we figured out that medications like Fluoxetine may be working by increasing BDNF.
As quoted from this paper....
These experiments highlight an important role for the serotonergic system in processes of histone remodeling [read epigenetic mechanism] related to depression.
Surely, that's got to be it?
Well no.
There is exciting new research that we will discuss in future blog posts. But briefly, human cells contain a "cytoarchitecture" (an internal frame work) made up of microtubules. And inside these microtubules light is whizzing around in tiny quantities (called biophotons). Research shows that Serotonin itself is literally affecting the microtubules inside cells [3,4] and is altering the light signalling [5]
And finally, a huge area of research shows that almost all disease has inflammation as an underlying cause. This last paper [5] gives a forth mechanism by which serotonin itself is working... by acting as an antioxidant and decreasing inflammation....
Quote from the paper...
Hence, we postulate two possible new roles for serotonin: (1) as an antioxidant, in order to counter-balance the oxidative effect of FAs, and (2) to participate in quantum interactions with MTs, in the same way as anaesthetics and psychoactive compounds have been recently shown to act.
Do the SSRIs effect microtubules and inflammation? Yes, this paper [6] shows that microtubular changes occur when SSRIs are used and there is clear evidence that SSRI's act as anti-oxidants. [7]
Well how exciting is that?!
What does this mean?
We already knew that 1) the microbiome, 2) Inflammation 3) the influences on our genes (epigenetics) and more recently suggestions that our 4) cellular light signalling mechanisms were all major determinants of our mental health. We now know that SSRIs are not just acting by changing neurotransmitter levels in the synaptic cleft. They are actually modulating these four systems.
So here's the thing. The increase in depression noted by the Lancet has occurred during the time that we have been using Prozac and medications like it. They are not preventing the problem. Meanwhile we all want to see a decrease in rates of depression.
The "pill for an ill" model of modern medicine is not going to do this for us and therefore is not working. So we need to go to the origin of the issue. We need to take an integrative approach to health. What will improve our microbiome, decrease inflammation, increase biophoton signalling and positively influence our epigenetics? The main answer is the food that we eat. We need to start looking after our soil and plants.
What we spray on them determines the health of our microbiome. Agricultural sprays designed to kill bugs aren't partial. They also kill bugs in our gut - (parts of the microbiome) when they arrive in our tummies on foods that we eat. They also cause inflammation.
What we do to our soil also determines the nutrients taken up by plants and therefore that are found in our foods. These nutrients determine how our genes are regulated (neutrigenomics or the epigeneitic modification of the activity of our genes due to nutrients). Research shows that food grown without agricultural sprays, generally has more minerals and nutrients and positive ratios of healthy fats (in the case of organic meat).
And it's time for us to start recognising the biophoton systems that we run on and what supports them. (more in future blog posts). The light in our cells, the things that fire us up and nourish our systems and give us positive energy, make the mitochondria in our cells able to produce ATP,... those sorts of things.
And if we do this, if we look after the soil, plants, each other and our earth...we will not only see rates of depression go down...
We will also be looking after creation. And that is a good thing all around.
[7] Bianchi M. al Fluoxetine administration modulates the cytoskeletal microtubular system of the rat hippocampus. Synapse. 2009 Apr;63(4):359-64. doi: 10.1002/syn.20614.
[8) Galecki P et al. The anti-inflammatory mechanisms of anti-depressants - SSRI's, SNRI's Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jan 3;80(Pt C):291-294.