Antidepressants Helping or Hurting

My Notes From the Depression Sessions

An Interview With Dr. Daniel Kalish DC

The Truth about Antidepressants: Helping or Hurting?

I have been studying this for over 20 years the first ten years were on hormone related conditions, adrenal, thyroid, female hormones things like that gut related stuff. About 12 years ago I started to focus more on the brain and toxins and how they impact the brain, how trauma impacts the brain and how we can work with brain disorders in conjunction with the hormone issue. I look at that as a neuroendocrine system but were going to talk about the neuro side, the neurotransmitters.

One of the leading problems for clinicians now which wasn’t the case 20 years ago is increased levels of toxins in the environment so were seeing levels of brain damage that didn’t used to exist whether it’s Autism in kids or adults with Parkinson’s etc. All these neurological conditions are exploding including depression I think clinicians of the next generation are going to be confronting brain related toxin issues it’s not just about stress and hormones anymore we have to deal with this too.

How the neurotransmitters work is one the nerve cells and there is what’s called the pre-synaptic neuron and the post-synaptic neuron they communicate using these chemical messengers we call neurotransmitters. You can think about it as kind of a water balloon inside the neuron or nerve cell you have these vesicles and inside the vesicles you have these neurotransmitter chemicals. There are different kinds serotonin, dopamine, epinephrine, norepinephrine, the idea is their stored inside the pre-synaptic cell. When your brain wants to have a thought, a feeling or something is going to happen to you you squirt them out into the space between the cells and they hit the post synaptic neuron receptor sites. The chemical leaves the first cell and hits the second cell and then that cell fires, that’s how we think, that’s how we feel, that’s the biochemistry of all our brain function. Just like a car you step on the gas it ignites a spark it’s an electrical conduction system basically, it is continuous one neuron firing the next in an intricate spider web. There can also be one neuron squirting out a bunch of serotonin that triggers a lot of them all at the same time.

Serotonin is the main neurochemical that we usually look at but there is four total when you talk about the drugs, serotonin is the most popular right now in terms of medications people are using it’s a feel good chemical. When you are low in serotonin you could get sad, depressed, not sleep so well, anxious, when your levels are good you feel good, your energy is good, you have a better sex drive, a better mood, sleep is better. The other three chemicals are dopamine, epinephrine and norepinephrine those together as a group are called catecholamine’s and they are as equally important as serotonin. Their considered excitatory neurotransmitters, they excite us and get us motivated while serotonin is inhibitory it calms us down and you need a balance of all these different chemicals to feel good every day.

Serotonin means Sero is by blood and tonin is tonifier when they first discovered serotonin one of it’s actions is it constricts blood vessels and before they understood it was a neurotransmitter that was operating in your brain they could see it outside the brain in the blood vessels causing things to constrict. Serotonin is both inside your brain and outside your brain, the serotonin outside your brain is mostly made in the gut and these cells in the digestive tract produce 95-96% of all the serotonin in the body so your gut makes it. In the gut itself it makes this peristalsis action or contraction of the gut that’s it’s job there, if you have a ton of serotonin you get loose stools or diarrhea and if you don’t have enough serotonin you could get constipated this is just serotonin in the gut unrelated to the brain levels. If people have IBS or those kind of problems sometimes they have constipation and diarrhea they go back and forth because their serotonin levels are going up and down. Entamoeba histolytica is a microscopic parasite a protozoa in your gut that actually produces it’s own serotonin so if you get the parasite it will cause you to have really rapid bowel movements.

SSRI’s suck the serotonin back into the cell that made it then the body puts it back into the vesicles where it’s protected, the SSRI’s lock the reuptake so the serotonin stays outside the cells where it’s more biologically active. Normally the serotonin hits the receptor the brain cell fires, the serotonin does it’s job and goes back to the first cell but when you take an SSRI the uptake of the second cell is blocked leaving serotonin to build up in between the cells causing more brain cells to fire. One of the reasons your brain pulls the serotonin back is because it’s protected when it’s inside the cell when it’s held outside the cell in between the cells it’s broken down by these enzymes called MAO and COMT they are all waiting to breakdown the serotonin and if they see it outside the cell they grab it and break it down. The reason your body has this intricate recycle system is because it wants to stimulate and protect, if you force the serotonin to stay outside the cell over time it’s going to get degraded or broken down at a much more rapid rate. Eventually you can force the serotonin to stay outside the cell but the overall serotonin in the system is going to drop, every year your on an SSRI the levels are going to drop. This means that you will have to increase the amount of SSRI that you are taking and this is well known with psychiatrists that they struggle with because one medication may stop working entirely and they will switch you to another drug that will work on a different series of transmitters.

For depression the numbers are staggering 1955 there were 38,000 people in the U.S. that were diagnosed as depressed the most recent numbers are nine million. Were not talking about a little bit depressed were talking enough to be disabled it’s the number two leading cause for people not being able to show up for work anymore. I think there is a trend to diagnose it more because there is a lot more medications for it but not enough to explain those numbers, world wide the numbers are increasing. I think part of the reason is toxins in the environment and the ability of neurotoxins to get into the brain and damage brain cells and diet. The toxins is interesting because of SNIPS single-nucleotide polymorphism, you could have a grandfather that was a farmer who raised crops but used a lot of chemicals who would pass on his neurotoxic load to either the child or the grandchild, sometimes they skip a generation. The children of today are dealing with the legacy of what their parents may have been exposed to and also their grandparents and that’s another significant problem.

There are multiple reasons why this can be depleted one could be diet where your not eating the right amount of protein or good quality protein or your digestion is not working well, if you can’t break down and digest your protein well your not going to be able to make these proteins. Another is intense amounts of emotional stress and a digestive problem so you would use up or burn up a lot of these chemicals and become depleted. There is a damage type where there is either neurotoxins or brain trauma, this is an important thing now with veterans they estimate that there are 450,000 veterans coming back from the war in the middle east who have traumatic brain injuries. This is also true for hockey players, football, boxers it’s all coming out in the news now that head trauma can cause the same damage as toxins.

We mentioned the bulk of the serotonin is produced in the digestive tract itself but the amazing thing is after you produce it in your gut it goes into your platelets. Platelets are if you cut your finger and it starts to bleed the platelets are responsible for coagulating so you don’t bleed out, they start to form a clot so the platelets are holding onto this serotonin because it’s a vasoconstrictor. You get a cut the platelets show up with the serotonin and they dump all the serotonin out so your wound can heal. There are multiple studies showing that when your on an antidepressant for three weeks 80-90% of the serotonin outside the brain is depleted because the reuptake ports that suck the serotonin back in they exist on the platelets too so your stripping out the serotonin outside the body as well as stripping it outside the brain so the SSRI’s are stripping it out of the inside and the outside of the brain. This is one of the reasons they have so many side effects leaving you at risk for all kinds of problems.

Peripheral serotonin has to do with the blood brain barrier that keeps some stuff inside the brain and doesn’t allow other stuff into your brain and interestingly one of the things it doesn’t allow inside the brain is serotonin. The same for dopamine, epinephrine and norepinephrine so if you make serotonin or these other chemicals outside the brain it stays outside the brain which means the serotonin inside the brain is exclusively made inside the brain. This is important for lab testing if your measuring the serotonin in the urine that bares a distant and complicated relationship to the serotonin to the brain because the serotonin in the brain is broken down into these little chemical particles and then it is excreted from the body so a lot of lab testing done is fraught with problems because of the blood brain barrier. When serotonin is broken down the little particles in the brain the metabolites are broken down the same in the brain as they are in the body. The serotonin outside the brain just goes to your kidneys and gets dumped out by the kidneys as serotonin so there is serotonin coming out in the urine but it’s the serotonin that is made locally not the serotonin that’s made in the brain. When your urine testing there is a very complicated relationship between the serotonin in the urine and the serotonin in the brain and that is new science that’s largely unexplored, for the most part. If you want to test the serotonin in the brain you have to get into the brain or the cerebral spinal fluid to see how much serotonin is in the brain and those are very accurate.

In the 1950s they were doing research studies on tuberculosis trying to help TB patients to overcome tuberculosis and they started to use these different kinds of drugs. They noticed these TB patients were getting abnormally happy obviously having TB is depressing, but they started to see a mood change and that’s how we got the first antidepressant drug. In those early days they had a different mechanism of action and they were called enzyme inhibitors or MAO inhibitors. When we talk about those enzymes that break down the serotonin or epinephrine, the original set of drugs they inhibited the enzyme so they blocked the enzymes from breaking down the chemicals so you would end up with more chemicals in the brain. It wasn’t until 1988 or so when they released Prozac that they started to use these drugs for a different purpose, rather than preventing the enzymes from breaking down they started using drugs that blocked the uptake. The conclusion is about the same either way you end up with more chemicals in the space between the cells by a different mechanism.

I was thinking about this the other day that if I brought my car to the car mechanic and they said there’s about a 10% chance this is going to work would you spend fifteen hundred dollars getting the breaks redone on something that had a 10% chance, you would think twice about it. All the research shows the SSRI medications are effective between 8 and 13% of the time range depending on which study you look at. The original purpose of these drugs is to be used when people have a major depression and major depression is pretty well defined these are people who don’t get up and put on their clothes anymore, they don’t leave the house, they don’t cook, maybe they don’t even bathe or shower, oftentimes they need to be institutionalized. In that small segment of people the drugs can be effective but when you start to bleed out and you start to use other groups who are mildly depressed or maybe not clinically depressed at all then you get into this 8-13% range. The interesting thing is most of the studies have a complete, people that receive some benefit are going to range between 50-75% in the study usually it’s around 50 on average, how is that happening well around 10% is from the drugs around 30-40% is from the placebo effect. In other words 3-4 times higher percentage placebo effect than the actual effect of the medication itself. I like the placebo effect I think it’s people healing, you go to a doctor you like this person, you trust them, they prescribe an antidepressant and you believe, it’s belief. I used to think a placebo was a negative but I think it’s the human spirit deciding it’s going to get better and placebo effect is actually growing over time. Placebo effect is getting stronger all the time people are believing more in this the effect of the drug stays about the same and the placebo is growing.

Antidepressants work for some people we just want to make sure we give them to the right group. There are four theories for how they work, the first one makes the most sense that your low in serotonin or dopamine or one of the others and you take this drug called a monoamine hypothesis and your low in serotonin you take the drug your serotonin gets better and that’s why they work. One of the major disconnects with the low serotonin idea is if that’s what’s happening why does it take so long for these drugs to work, days, weeks, months for some people it’s consistent that it takes a while for these drugs to kick in and start to work. If these drugs bring the serotonin levels up quickly why does it take so long to help, there is a group of scientists researching this and they think the problem is high serotonin. If you have high serotonin the theory is that there is down regulation of the receptors with the serotonin neuron you have these receptors on the second cell. You have the presynaptic nerve so the neuron is making the serotonin and it’s squirting it out into the space between the cells and the reuptake is being blocked. Usually what would happen is the serotonin gets made it hit’s the first cell, it gets recycled back into the cell that made it and stays here, when you need it again it squirts out and recycled again. These medications inhibit the uptake, their blocking the uptake process, it’s like a vacuum cleaner that’s clogged so the serotonin stays outside the cell for a longer period of time. When it’s outside the cell some bad things happen enzymes break it down which overall can deplete your serotonin levels, for a short period of time it’s going to improve your serotonin levels and make the person have a better response in terms of how their neurons are fired. The high serotonin people think what’s really happening is that the serotonin levels were never low in the first place they have actually been high the whole time and the high serotonin is the original problem so why do these drugs work is they make the serotonin even higher. Imagine that you have high serotonin you take these medications that raise up the serotonin even more, these receptors down regulate they see a high serotonin getting even higher and so they slow down. It’s like a car speeding up and you put the breaks on causing them to be serotonin resistant according to this theory we don’t know if this is true or not yet.

The third group these are like neuroscientists that are trying to figure out this puzzle of why this is happening. They think high serotonin is the problem but it’s down-regulation of what’s called an auto-receptor. Imagine this presynaptic neuron and you need to have a general sense of what’s going on in the outside space between the cells, you have an auto-receptor that reads the levels of the serotonin outside the cell to tell you what’s happening. If your a serotonin neuron and you make 100 units of serotonin you have to know that happened so you have a receptor and make the serotonin and most of the serotonin goes out and starts to do stuff. Then the serotonin comes back and tells the cell you just made enough serotonin you can stop now the auto-receptor is gauging the levels of the cell. They believe the levels are too high to begin with and you give a drug the levels go up even more and the receptors go whoa the levels were bad before but now their really bad so they shut down serotonin and tells the cell to make less. The fourth theory we have this competing idea that there is low serotonin and 2 groups of neuroscientists saying no it’s high serotonin but they disagree on why, different receptors and the last group that think all these people are wrong. The fourth group thinks that it’s damage to the receptors that’s actually the problem and don’t think it matters if your serotonin is high or low what matters is what’s happening with the postsynaptic neuron. If your a football or hockey player and you get hit in the head a lot or your a veteran and your in an explosion you get damage to the postsynaptic neurons.

One of the things that I think is happening to a lot of us is you have a neurotoxin damaging the postsynaptic neuron, inflammation from poor diet and inflammation of the gut can also cause this. In this model it’s damage to the postsynaptic neuron that matters, lets say you have 100 postsynaptic neurons and 50 of them are gone this theory says that if we increase the serotonin, double it we can get these 50 that are left to fire twice as often and restore normal function. This theory could explain why people with normal serotonin can be depressed because you can have normal serotonin but damage to the receptor and be depressed because that’s where the effect happens. This last theory explains a lot of different variables because it says that even if you have normal serotonin you could still have a problem but increasing the serotonin get’s better firing, it gets the remaining neurons to fire properly. There are some basics to repair these neurons, removing neurotoxins, doing detoxification protocols, trying to protect the brain cells to flush out toxins and start to rebuild. We also do a lot of work if it’s indicated in trying to restore normal neurotransmitter levels with different nutrients. What I think is really going on and I thought about this for 12 years, I think there are some people that are actually low in serotonin. They go on a paleo diet and their depression is gone, you get rid of a gut bug, stop eating gluten and their depression is gone, probably just restoring something that was deficient but that doesn’t work with everybody. I definitely think this is pretty complex and the body is usually pretty simple when you actually find out what’s going on and the damage to the receptors is definitely going on, we see that all the time I think it’s a combination of both and some genetics.

These drugs aren’t without their pretty powerful effects one of the long term effects, imagine your whole brain and you have 1000 units of serotonin in your brain what the drugs are doing is changing the location of the serotonin from inside the cell to outside the cell forcing it to stay outside the cell so there is no net increase in the amount of serotonin you still have 1000 units it’s just in a different place. Because we move it outside the cell with these medications the enzymes are breaking it down at a much greater rate so every year your on these drugs the total amount is dropping steadily because the enzymes are chewing it up. The reason we even have a recycling system to bring it back in is when it’s inside the neuron the enzymes are not able to get at it it’s protecting it. There is a wonderful book on this called Anatomy of an Epidemic by Whitaker and he goes into a lot of the long term studies if you look at the studies over a course of 6-8-12 weeks you see certain effects of these medications. When you look at it over long periods of time it’s different and when you look at medicated versus unmedicated people over long periods of time it’s different as well. What happens pretty clearly and consistently throughout all the research people who take medications for initial depression are at about double the risk of having a second or later depressive episode. People who are very depressed and do not take any medication at all within 6-12 months typically come out of that depression even though their not treated in any way it just gets better on it’s own. Those people that are not medicated have half as much chance of becoming depressed later and some of it is because these medications decrease the amount of serotonin in the brain overall and it’s also potentially related to Steve Hyman’s work in terms of what happens to those receptors when we take these medications.

Quote from Dr. Hyman: The mechanisms by which drugs of abuse produce dependence are better understood than the mechanisms by which antidepressants, antipsychotics and lithium produced their therapeutic effects. Basically he is saying cocaine, speed, heroin we understand these drugs better than we understand these prescription medications.

For those that have been on antidepressants for years you don’t want to just stop taking these medications suddenly because that can make you worse. You definitely have to find a team of people to work with usually a psychiatrist and someone who’s more alternatively or integrative, sometimes you can find an integrative psychiatrist but that’s pretty hard. You need someone who can handle medications and someone who can handle supplements and do the work that you need to do to bring these levels back up. We always want to get the chemical levels back up using various supplement protocols then once the brain is starting to heal and repair the psychiatrist can taper them off the drugs and that can be a multi year process it can take people a year or two before they can achieve all that. Supplements means specific vitamins, minerals, amino acid therapy and cofactors, it turns out some nutrients are critical B6, calcium, vitamin C and then there’s amino acids like 5HTP and tyrosine depending on what chemical imbalance is being created by the medications.

Meditation does make a difference, if you take away the major depression category are we trying to medicate normal human experience, it’s normal to be sad if someone dies, it’s normal to be upset if you split up in a relationship. For the most part I see these drugs being used to make people who are overweight and tired happier and make people who are going through emotional trauma happier and I think it’s robbing us of our humanness and our human experience. I think things like spiritual practice and spiritual disconnection is at the foundation and the reason why people are turning to these drugs their trying to solve a spiritual emotional crisis with a medication which really wasn’t designed for that purpose in the beginning. I feel like meditation, if your not into that then an emotional connection, emotional work and having a community of support makes people resistant to these kinds of problems.

I do patient consults two days a week and work with people over the phone. I am putting together a four week course for patients that will be starting August first it’s an online program that goes over all brain related issues and repair

Dr. Kalish web page for patients is

For the doctor training programs it’s


Disclaimer: The information contained on this site is for educational purposes only and should not be used as a substitute for diagnosis or treatment rendered by a licensed physician. It is essential that you discuss with your doctor any symptoms or medical problems that you may be experiencing.

M. Scherker medical researcher