Food First, Pharma Last: Part Two of our Interview with Chris Masterjohn

Welcome to the Mad in America podcast. My name is Brooke Siem, and I am the author of the award-winning memoir on antidepressant withdrawal, May Cause Side Effects. Today I am back with Chris Masterjohn, PhD. Chris is a nutritional scientist, former professor and founder of Mito.me. With a PhD in nutritional sciences and years of research in mitochondrial biology, his work focuses on translating peer-reviewed science into practical tools for human health.

At Mito.me, Dr. Masterjohn pioneered the first analysis designed to measure mitochondrial respiratory chain function directly, identifying individual energy bottlenecks and guiding personalized science-backed protocols to optimize the system responsible for over 90% of cellular energy production. His mission is to bring mitochondrial testing out of the rare disease space and into everyday health.

If you haven’t listened to part one, I recommend that you go back and give it a listen. We do get into a lot of the nitty-gritty science of Chris’s work and its connection to serotonin and antidepressants. We are going to do a little bit more of that here before getting into more practical strategies and how we can take Chris’s work and apply it to the day-to-day life of people recovering from withdrawal and psychiatric drugs.

The transcript below has been edited for length and clarity. Listen to the audio of the interview here.

Brooke Siem: Chris, thank you for taking the time to come back and talk with me.

Chris Masterjohn: Thank you for having me.

Siem: We’re just going to jump right into it because last time we were talking, we ran out of time just as we started to talk about the Sigma-1 receptor. The reason this is important is that when it comes to antidepressants, we spend a lot of time talking about serotonin and serotonin receptors and the serotonin system. But you have hypothesized that another receptor called the Sigma-1 receptor is quite involved when it comes to antidepressants, and it may help explain why withdrawal can be so difficult for some people. If you wouldn’t mind explaining a little bit about what the Sigma-1 receptor is and why it matters in this context, I’d really appreciate it.

Masterjohn: The Sigma-1 receptor is still poorly understood in terms of its overall function, but we at least know that it appears to be involved in the stress response because it is necessary for the response to cortisol. We can at least say that it sounds like something that should be activated cyclically and rhythmically, although irregularly, according to how stresses go up and down in a person’s life.

Now, we can look at what its function is from a number of different angles. For example, if you just knock it out in mice, meaning you delete the gene for it so they don’t possess a Sigma-1 receptor, they have a pretty interesting response. On the one hand, they are less likely to despair when put into restraint stress, so they’re less likely to give up, and they seem to fight back more effectively.

But on the other hand, they seem to have other signs of a dysregulated stress response. For example, they are more likely to be depressed, and they have a more chronically activated hypothalamic-pituitary-adrenal axis.

Siem: These are big words for our audience. Can you dumb that down for me?

Masterjohn: Okay. Cortisol, you could think of as your main stress hormone, and it is considered a glucocorticoid because it’s made in the adrenal cortex, which is part of the adrenal gland, and gluco because its main purpose throughout the body is to increase the amount of blood sugar you have so that you can drive more fuel to feed your brain during acute stress.

If the Sigma-1 receptor is involved in the response to cortisol or the response to stress, that would explain why, if animals don’t have it, they have a more chronically elevated stress response because their cells are not responding to the stress hormones, so they’re trying to compensate for that by making more stress hormones. Whether that leads to them being in a more stressed state or not is unclear. But it looks like they have various personality-like changes, some of which are good, but others which are largely irregular and negative.

So the simplest high-level way to explain that is that the Sigma-1 receptor is essential to the stress response. You want it to be intermittently activated by signals that are natural to the stress response. You don’t want it chronically activated, and you don’t want it chronically under-activated. Now, if you look at what it is doing inside the cell, what is it trying to do? It appears to do a whole host of things that are natural to certain types of cellular stress. One of the things it does is improve mitochondrial energy production in general. That makes sense because when you’re under stress, your body perceives that there’s a need to use energy quickly to fulfill the demands of the fight-or-flight response.

However, another thing it does is it helps the cell in a very similar way to how I described serotonin in the last podcast that we did. It helps the cell respond to a relative deficit of oxygen. It’s activating something that’s poorly understood in the mitochondria, that is allowing the mitochondria to do what it usually does with oxygen when there’s not enough available. In that sense, it shares a lot with serotonin. When you take SSRIs, you get too much extracellular serotonin. You block the ability to transport it inside the cell. Those responses are really going haywire on SSRIs.

When your body is perceiving that you have less oxygen than you need in the moment, more serotonin is released. Serotonin helps the mitochondria adapt to that state, and helps them rise to the occasion and helps distribute oxygen to them. The Sigma-1 receptor is doing something very similar to that. Part of that might actually be by increasing the amount of intracellular serotonin, both by increasing the synthesis of serotonin and also by increasing the transport of serotonin.

The cell has two ways of getting serotonin inside it. One is to transport it from outside the cell to inside the cell, which is blocked by SSRIs. The other is to make new serotonin from the amino acid tryptophan, which comes from the dietary protein that you eat, inside the cell.

Those are two ways for serotonin to get inside the cell. It has to be inside the cell to have the full spectrum of its beneficial effects on mitochondrial function. The Sigma-1 receptor is at least in part acting by making more of the serotonin transporter, although that’s blocked by the SSRIs, and also making more new synthesis of serotonin inside the cell. That’s at least part of why it’s playing a role in helping mitochondria respond to the oxygen deficit.

Now, as to what is supposed to bind to the Sigma-1 receptor, there’s been a search for the endogenous ligand. The ligand is something that binds to something. Endogenous means not a drug, but something that normally exists in your body without you having to put it there. There are a bunch of candidates, but no one really knows exactly what is usually the thing that binds to the Sigma-1 receptor. Now, we know that SSRIs go inside the cell. After they block serotonin from getting into the cell, they go into the cell instead. Once they’re there, some of them activate the Sigma-1 receptor quite strongly, and others don’t. There’s a 52-fold variation between the different SSRIs.

I think that is a big part of what causes heterogeneity or variation between people’s different experiences in SSRI discontinuation, as well as what works to help different people. I think that’s also why the animal experiments on what SSRIs do to brain serotonin levels are so discrepant.

I mentioned this last time, but people who make claims about what SSRIs do to the brain don’t have good evidence at their disposal. It’s just unfathomable to me that there are only a handful of animal studies that even address this topic, and they find opposite results between them.

I think the reason that the animal experiments conflict is because they’re done with different SSRIs, and the effects of different SSRIs on brain serotonin are different. The people that have published some papers on animal experiments that they’ve done are just making the assumption that the SSRIs all do the same thing to brain serotonin, and they will just use different SSRIs interchangeably in different animal experiments, and they get different results, but they can’t explain the details of what they’re seeing because they’re not recognizing that these two SSRIs are doing the opposite thing to brain serotonin. That’s a huge problem because all the hypotheses to try to deal with it are conceptualizing it as if its rebound effects from removing the impact on brain serotonin.

I don’t think the rebounding of serotonin or secondary neurotransmitter systems acting on the levers of personality and cognition, I don’t think that’s where the answers lie. Part of the reason is just the massive differences between the different SSRIs and how they impact those systems.

Siem: Psychiatry is all about emotions and mood, and acting in ways that are unpleasant to society. I think a lot of the withdrawal world, even in the language that patients use, is just all about how you’re feeling. What I’m gathering from your work is that I think it would be really interesting if we started maybe focusing less on the emotion and more on the physical side effects, physical symptoms, because I’ve really seen in the hundreds of folks I’ve talked to at this point over the years kind of clusters of different kinds of symptoms that tend to affect people. I think if we started looking at it from that perspective, we might start to see patterns that might reflect everything you’re talking about.

Masterjohn: It’s interesting that you bring that up. Another kind of what I suspect is a false lead is to make arguments about the half-lives of different drugs and try to explain them based on the rates of discontinuation. I thought what was interesting about one of the, or probably the only major investigation of brain zaps, was that the drugs that had a longer half-life just caused a proportionally longer number of days to the onset of the brain zaps, but they didn’t have any impact on the incidence of brain zaps. I thought that was interesting.

I do think that symptoms are often important clues to things. But I also think that symptoms can be incredibly misleading in terms of trying to signal something about the underlying pathology. I think that most people and most doctors generally put too much emphasis on analyzing symptoms to the detriment of figuring out what they are. If your primary problem is an energetic deficit, then whatever that’s going to manifest in is going to be your weakest links that have nothing to do with energy metabolism.

For example, if I have some kind of latent vulnerability because of my genetics, my nutritional history, my trauma history or whatever goes into who I am today. If I have some kind of latent predisposition to dizziness, in an energetic deficit, I’m going to be more likely to get dizzy. But if I have some kind of predisposition to muscle pain, in an energetic deficit, I’m going to experience muscle pain. If I have a genetic predisposition to anxiety, in an energetic deficit, I’m going to get anxiety.

I don’t at all want to throw out symptoms as guidelines or as rules of thumb or as potential clues to what’s going on. But I do think it’s important not to get stuck in overemphasizing them because you could have heterogeneric or highly variable manifestations of something, but you could have a very homogeneous or very sort of universal underlying feature of what’s driving all of it. The fact that one person got brain zaps and not restlessness, and another person got restlessness and not brain zaps, I don’t think that’s telling you that those two people are suffering from two totally different things. I think that’s why we need a ton of research on this, because I think what we’re going to find is that there’s going to be some common themes of how the underlying metabolism is dysregulated. But the most universal thing is going to be that the underlying metabolism is dysregulated.

Siem: That’s really interesting, because, again, if we look at the physical versus mental and emotional side of this, when it comes to the mental and emotional side, often it seems to reveal the weak link or just the old issues, whatever the reason why someone was medicated in the first place. Those things tend to come roaring back in withdrawal, and it just puts a magnifying glass on it.

It never really occurred to me that that could be happening from a physical standpoint, too, where we are sort of revealing the weak link, if you want to call it that, or where a person’s most likely to struggle. But this makes a lot of sense to me when we’re talking about full-body cellular chaos, basically.

Masterjohn: I think that this is not a fruitful place to make progress with people who are skeptical from the medical establishment, because they’re going to say, “Of course, it’s returning because you took them off the medication that was helping them.” The way I look at it is that you had an energetic problem in the first place. That’s why that predisposition manifested into what it was, and we could go back to stuff I mentioned in the last episode, like why is depression threefold higher at levels of high altitude? Why are people with insomnia having twice the risk of having depression in the future? I think those things come down to an energetic deficit driving the predisposition.

You can convince me about that, but for sure to do the research that’s going to convince the establishment, we really need to focus on the things that are obviously not a return of the original thing the person was medicated for. I think that’s why the science on this is so compelling, because there are so many things to point to that are obviously not a return of depression.

Siem: When we started talking about the Sigma-1 receptor, I started digging around a little bit, too. One of the more fascinating things that I came up with was the Sigma-1 receptor and its connection to neurodegenerative diseases like ALS or Parkinson’s. The reason why I’m asking this and we’re really going into the world of theory, hypothesis, and just brainstorming here, which I cannot overstress enough, because neither you nor I are medical doctors, and I don’t even have a master’s degree, so let’s start there.

But when we’re talking about symptoms that show up that didn’t exist before, right, one of the most devastating and difficult for people to endure is akathisia. Akathisia, when it’s more serious, can look a lot like Parkinson’s or something where there’s this shaking, there’s this tremoring, and I just couldn’t help but wonder if maybe there’s some connection between SSRIs activating or not activating Sigma-1 and then withdrawal, people having akathisia. I just thought it was very interesting, even though obviously the pathology of akathisia is not the same as Parkinson’s or ALS.

Masterjohn: Well, I think Parkinson’s is really easy to make a super clean story about. ALS is, I think, a little sloppier. But in animals, one of the primary Parkinson’s models is to just give them the fish poison rotenone, which is a specific inhibitor of Complex 1 of the mitochondrial respiratory chain. If the mitochondria are the powerhouse of the cell, the respiratory chain is the engine cylinders, and they drive the production of energy, and they’re named after their different complexes. If you look at the Sigma-1 receptor, one of the most specific things it does in the mitochondria is it activates Complex 1. It does the opposite of rotenone.

I think you could make an argument there. I do think that the actual pathology of Parkinson’s is not so simple. But if you just look at those couple of things, it looks like the main driver of Parkinson’s is how inhibited or activated your Complex 1 is. Parkinson’s is a great example of how you should think of your total energy production as if the majority of it is just used to produce stuff and maintain and repair stuff. But the last 10% or 20% of the energy you produce is used to control the distribution of all the rest of the energy.

I guess what I’m saying is that Parkinson’s and akathisia and anxiety might all be manifestations of not distributing your energy in a productive way, and they’re just variants on that theme. If we go beyond this enormous significance of Complex 1 of the mitochondrial respiratory chain for Parkinson’s and just look at what the main theory about how it happens in the first place, it’s a degeneration of the dopamine-based neurons in the basal ganglia that are controlling movement. But what do they control about movement?

Dopamine in the basal ganglia is signaling a subconscious calculation of the value of investing energy in something. I think it’s like anxiety is over here and Parkinson’s is over here, and akathisia is kind of in here somewhere, but it’s just another manifestation of not controlling where that energy is going.

Anyway, in terms of the Sigma-1 activation, I think that might indicate that there’s a specific Complex 1 relevance, kind of like there is for Parkinson’s. I think a lot more research is going to have to be done on that. But I definitely think that dysregulation of the Sigma-1 system should be highly suspect for discontinuation problems from SSRIs, especially if what you’re withdrawing from is a powerful Sigma-1 activator. That’s all the more reason to suspect it in that case.

Siem: Can you just quickly list the more powerful Sigma-1 activators versus the ones that don’t do all that much, just quickly for the audience?

Masterjohn: There’s a 52-fold variation between them. You could generally say that paroxetine is trivial. Citalopram and escitalopram are kind of weak. Fluoxetine is in the middle, and fluvoxamine and sertraline are the powerful activators. Sertraline is an incredible gray area because there are some studies where they looked at models of what sertraline versus fluvoxamine do, and even though they’re both powerful regulators of the Sigma-1 receptor, in some endpoints that are thought to be Sigma-1 related, they do opposite things, and that might indicate that sertraline is actually a very powerful inhibitor of it. We’re very much into the gray area when trying to separate fluvoxamine from sertraline. But you could at least say that, for example, paroxetine, super weak, probably not relevant. Citalopram and escitalopram are pretty weak, probably not relevant. Then, for the other ones, I think you could posit some relevance.

Siem: Great, thank you. I think if nothing else, what this does is that it just proves how much more complicated this all is than even most doctors understand, and anytime I can make a doctor start to question things, I like it. That’s why I asked.

Masterjohn: Well, I don’t think almost anyone who’s prescribing SSRIs has even heard of this Sigma-1 receptor.

Siem: Let’s move on a little bit. I want to focus on more practical things that folks can do for the last 25 minutes or so of our time together. One of the things we talked about in part one was that at any point, certain cells in our body can be in a hypoxic state, which means they don’t have enough oxygen. That there’s a correlation between high altitude, which means there’s less oxygen in the air and depression. That starts to make me wonder about breathing exercises, and could breathwork in some way or some sort of hypoxic training perhaps be beneficial to folks who are in withdrawal?

Masterjohn: Well, let me just say at the outset that I’m sure you’ve covered this with other guests, but I do think the extended taper should be the kind of basal, how am I going to get off this with minimal problems? But that said, I do think that everyone should practice breathing exercises because almost none of us breathe that well. James Nestor has a great book, Breath, that covers all kinds of breathing exercises.

First of all, you should exhale fully. In general, that means it should take six to six and a half seconds to exhale. Then you should inhale fully, which should take a similar amount of time. None of us is going to breathe like this all the time, but if you set aside 10 or 20 minutes a day where you are paying attention to your breath, these are some things that you could try to pay attention to, and then you build better habits as time goes on. Then I do think that you should be trying to utilize your entire chest cavity in a three-dimensional structure without letting your belly hang out, and while also maintaining your shoulders relaxed. But you should be able, for example, to breathe into your upper back, your middle back.

You should be able to lower your diaphragm to breathe into your deep belly. Most of us are missing something like that. Like for me, it’s super easy for me to breathe with my gut hanging out. If I try to breathe into my upper or especially my upper back, but into my mid-back too, I just get this incredibly powerful stretch. I do 50 deep breaths every morning to try to work on that. Although for me, it’s less about trying to manage a health problem and more about trying to restructure my body.

I think most people are missing some of the low-hanging fruit they should be doing for their health. Everyone should be doing those things before they’re trying to work on idiosyncratic stuff. I do have an article on my website, what everyone should be doing for their health, and so there’s a checklist there. But breathing through your nose and breathing fully is one of the items on that checklist.

I don’t know if it has specific relevance to SSRI stuff, but it has energetic relevance to everyone, and therefore, everyone should be doing it. I’m sure most people who are suffering from SSRI discontinuations are not doing it.

Then, hypoxic stress is the flip side of that coin. Training yourself to be more hypoxia-tolerant. I’m very bullish on this, even though the only thing that shows that it helps with depression was an animal study that shows that it’s 20 times more robust than antidepressants. I think that’s a big signal. I think when you look at the fact that depression is so strongly correlated to altitude, I think that’s a big signal and just the role of serotonin in handling hypoxia. I think those are all big signals that we need some type of hypoxic stress.

In the new year, I’m going to be doing some biochemistry experiments on myself. In fact, I’m going to take the Mito.me test, and I’m going to retest it at various intervals, spending different times in the mountains. But I’m also going to be running a bunch of blood tests on hypoxia response and hormonal changes. I’m very interested in the idea that we can take the randomized controlled trials that have been done in athletes showing increases in testosterone, and we can use that as kind of dosing amount for how much hypoxia is good in general for people.

In those studies, they got the maximum benefit from doing 10 to 12 hours a night for three nights a week and continuing it indefinitely. I’m really hoping that you can condense those 36 hours a week into five days in the mountains per month. If this is true, if I can show this is true in the study, I think we could use it in the corporate world to leverage some universal five days in the mountains for the five-day retreat once a month in the mountains or whatever.

But anyway, there’s a lot to know about this, but first of all, if you do live at altitude, you probably are not getting enough oxygen. The deep breathing thing, go to an oxygen bar, get an oxygen machine, take a vacation somewhere that’s at sea level, see if any of those things help. But if you’re at sea level and you’re depressed, you might need more hypoxic stress training.

I know people are so confused. They need to listen to this like 15 times to get this. Hypoxia is always relevant to everyone in every breath you take, when you get up in the morning or when you exercise. It’s not something that’s conditional on you living at altitude or having a lung disease or being strangled or drowned.

Every time I say something about hypoxia, I get so many people that are misunderstanding what I’m saying. If you live at sea level, you probably are not getting enough hypoxic stress. If you live at an altitude, you’re probably getting too much. Both of those things play a role in energetic dysfunctions that could contribute to depression or to problems getting off SSRIs. Trying to get into the happy medium, the middle ground that seems to be associated with maximal health is something like 80% of your time at sea level and 20% of your time at 6,500 feet.

Obviously, to say that everyone needs to do that is a little crazy. So to figure out exactly how to apply that to everyone, we’re going to need a ton more research, but it’s something you can play around with.

Siem: When I was in withdrawal and I was recovering, I started getting a lot into the breathwork world through Extreme Performance Training with Laird Hamilton and Gabby Reece. Then I also came across Patrick McKeown’s book, The Oxygen Advantage. What I realized through all of that is that if you start doing some basic breathwork protocols with people, they kind of tell you where their issue is. If they can’t breathe through their nose and take a walk, they’re probably pretty CO2 intolerant and definitely would benefit from some hypoxic training.

Masterjohn: Or they just never go for walks.

Siem: Or they just never go through walks. Then you can go the other direction, too. There are people who, you ask them to try and slow down their breathing, get really uncomfortable. You can kind of tell if you start working on it a little bit.

But I did want to mention The Oxygen Advantage because it’s a fantastic book from a protocol standpoint of things you can do at home just to learn. Whereas Breath by James Nestor is a really damn good story with a lot of great information. It’s a really entertaining read, as well as being just filled with incredible information about breathing.

Masterjohn: It does have an appendix with a bunch of different breathing exercises in it.

Siem: Let’s move a little bit into nutrition. I would want to caution on any sort of blanket supplementation recommendations because a lot of times, people in withdrawal are hypersensitive to supplements. But what I’m curious about is from your nutritional background, let’s go back to the low-hanging fruit. What should people be eating to support their mitochondrial health and, therefore, hopefully help them through withdrawal?

Masterjohn: I believe in a food-first, pharma last approach. The food first part of that doesn’t just mean food before pharma. It also means food before supplements. Supplements are meant to supplement a good diet, not stand in the place of one. And most supplements are dosed way too high.

They’re dosed way too high for two reasons. One is that there’s a widespread belief that taking more vitamins than you need just gives you expensive urine, meaning you paid for the supplement and you just peed it out. That’s total nonsense.

Supplementing with high doses of a vitamin can cause some pretty massive problems from imbalancing with other nutrients. You’re maybe not going to wind up with toxicity, but you might wind up with high blood glucose or anxiety or jitters or sleeplessness or whatever. I generally advocate that if you have a specific need to increase riboflavin, for example, I would do a very slow titration up with riboflavin-rich foods, which are things like liver, heart, kidney, almonds, to a lesser extent, milk, red meat, and salmon. Then microdose the riboflavin and go up at six milligrams at a time.

There are two ways to microdose supplements. One is to see if there’s a liquid version available, in which case the dose is probably measured as the whole dropper, and you can get one 40th of it by using a drop, providing you don’t have any digestive problems with whatever it’s dissolved in, which is usually glycerin. Then the other is to empty out capsules. You can get a milligram scale if you want to be precise. I think that even people who think that there’s no negative effect to a supplement they’re taking, often there isn’t any negative effect for the first one month. But 7 to 12 months down the road, you’ve become just massively imbalanced in your nutritional profile.

I’ve come to the belief that most people should just act like they’re very sensitive to nutritional supplements. It might seem like real overkill in the short term, but over a one to three-year time horizon, you’re going to be so happy that you didn’t wind up on some bag full of things that were giving you 37 imbalances and trying to figure out what they were on the back end of that.

In terms of the mitochondria, they depend on all the nutrients, and the easiest way to get all your nutrients in is to work in a small handful of major super foods, and then follow some basic benchmarks for the rest of the diet. I would say, to the extent you eat animals, try to eat nose to tail, which means try to eat all the organs, try to eat the bones, but at least work in liver and bone broth. If you have to, if you’re looking for the next organ meat to work in, I would say heart.

A lot of people are pinching their nose right now, but you would be surprised if you blend in a bunch of organs into ground beef.

Siem: Yeah, you don’t even notice it.

Masterjohn: So there are various companies like US Wellness, North Star Bison, White Oak Pastures, there are a bunch of different ones where they produce an organ blend that you can just buy as ground product. You just cook it with taco seasoning or something into crumbles and put it in a taco, and you’re not even going to know the difference.

A lot of nutritional yeast is fortified with vitamins, but Sari nutritional yeast is one example of an unfortified nutritional yeast, where it is naturally very high in B vitamins, but not anywhere near as high as the supplements you would get on the market.

Then I would say oysters. One or two oysters a day could be a nutritional miracle for a lot of people. Then just more broadly, I think you want to eat most of your food not at restaurants, eat mostly unrefined foods, not junk food, try to diversify across the proteins that you tolerate, and try to diversify across the carbohydrates that you tolerate.

For example, don’t eat all your carbs as bread; try to work in legumes like lentils, peas, and beans, and try to work in tubers such as potatoes. Diversification is a great protection against ignorance. You don’t have to eat a diversified diet, but if you don’t want to develop an expertise in nutrition and you don’t want to do dietary vitamin and mineral tracking, although I recommend people do at least for a few representative days, Cronometer is a great app for that.

If you have an allergy or an ethical restriction or whatever, you know, put a box around that, but otherwise try to diversify your nutritional portfolio. Make sure you’re eating foods that you digest, eat things that help your digestion with every meal like fermented foods or ginger or bitters, things like that.

Make sure you’re getting some fresh, minimally cooked or raw fruits and vegetables. Strawberries and bell peppers are really great examples of where you can get enough vitamin C from. Then that’s going to take care of most things. Salt your food to taste, is going to take care of the salt. Probably the one thing you need to think about after that is calcium. You should have three servings of a calcium-rich food that could be dairy or it could be bones.

But if you’re doing just plants, you have to be pretty selective. Bok choy and napa cabbage are pretty good sources of calcium. Broccoli and kale, those are your top greens for the typical American grocery store. But even those, you need to eat a lot of them to get enough calcium. I do think that it’s so much easier to get your calcium in if you’re eating either dairy or bones. When you’re doing bones, you do want to look for a clean source because bones can be contaminated with lead.

Do opt for pasture-based when you can. If you’re using a bone meal powder, try to get one that has a certificate of analysis showing it’s lead-free, things like that. But I think those cover the nutritional bases for most people and are an excellent starting place if people aren’t there yet.

Siem: I have one more question for you just based on everything I’ve learned about your work and talking to you over these past couple of episodes. What would you say to child psychiatrists who are putting kids on antidepressants?

Masterjohn: Well, I would say something to psychiatrists in general first. There was a randomized controlled trial a few years ago that randomized psychiatrists to either answer the question “what would you do for yourself if you were depressed” versus “what should I do if I’m depressed—what would you do if you were me?” Eighty percent of the psychiatrists said that they would put the patient on an antidepressant, but only 40% of psychiatrists said that they would put themselves on an antidepressant. But 80% of the psychiatrists told the patient that if they were them, they would go on an antidepressant.

I think the most generous way to interpret that is that the psychiatrist is thinking in their head, I can handle depression without a drug, but you can’t. If I were you, I would be like you, unable to handle depression without a drug. Therefore, I’m going to tell you that if I were you, I would take the antidepressant. There are more cynical interpretations than that, but I think that says that there’s a huge problem in psychiatry of not having confidence in their patients.

In terms of the children, I mean, if you don’t know what SSRIs are doing at the molecular and cellular level, which I know you don’t, you shouldn’t be putting them in kids because we have no idea what that does to the process of development. In a well-formed adult, you can be wrong about something, but you have a much better chance of erasing the error. You have a much lower chance of erasing the error when you make a big mistake in a kid.

I think that, in general, we need way more metabolic studies of what these things are doing on the whole. I don’t think most people who are prescribed them should take them, but I think that it’s a worse malfeasance to be putting kids on them.

Siem: Having been a kid who was put on them, I’m constantly trying to untangle what of this was my development being interrupted. The more I learn about how they’re affecting us and not just our emotions, it’s just infuriating to me that this is continuing.

All right, Chris, thank you so much. Do you have any final things for our audience, and where can they find you?

Masterjohn: I’ve written an incredible volume of stuff about this. So go to chrismasterjohnphd.substack.com and search for “SSRI” or just put in “Prozac, is it a performance-enhancing drug?” That’s the beginning of the series. Then you can just click the bottom of it and read the whole thing. The mitochondrial testing I have is at Mito.me, and I look forward to seeing people on both.