Think Differently. Solve the Impossible.

The guest today is Dr.

Rebecca Allen.

Dr.

Allen has authored papers and participated in research on Transcranial Magnetic Stimulation Therapy.

That's TMS, a type of brain therapy for one of the treatments for depression we're going to be talking about today.

She is trained in the neurobiological basis and treatment of cognitive and behavioral manifestations of neurodegenerative diseases, including dementia, multiple sclerosis, epilepsy, stroke, brain tumors, developmental disorders, traumatic brain injury and other disorders.

Dr.

Allen's current focus is on a brain stimulation and interventional treatments for neuropsychiatric conditions, including transcranial magnetic stimulation, the TMS we're going to talk about, electroconvulsive therapy, that's ECT, another treatment we're going to talk about, vagus nerve stimulation, ketamine, and esketamine.

As a doctor of research, she oversees clinical trials for these novel therapies.

She has held local and national leadership positions, including serving as a member of the board of the Clinical TMS Society, chair of the Insurance Committee on the Clinical TMS Society, president of the Clinical TMS Society, and president of the Washington State Psychiatric Association.

She has also altered a chapter on sleep and sleep disorders for the Harvard textbook, Neuropsychiatry and Behavioral Neurology Principles and Practice.

Before I start speaking with Dr.

Allen, I want to announce the contents of this podcast are for informational purposes only.

This podcast and the information it contains are not intended to be used as medical advice or diagnosis.

If you have questions regarding medical condition, ask your doctor.

If you think you're having a medical emergency, call your doctor or 911.

If you're in crisis and feeling suicidal or feeling you might harm yourself, call 988.

That's the suicide and crisis lifeline.

You can also text 988.

Welcome to my show, Dr.

Allen.

Thank you.

It's so nice to be here, Dan.

So first, tell us what depression is.

What does it feel like to have clinical depression versus a bad or sad day?

Because some people, probably a lot of them, don't seek treatment because it's like just having a bad day.

Doesn't everybody feel like this?

I think there's two ways to think about how depression is different from a bad day or a bad life period.

One is the severity and how pervasive it is.

So in order to be diagnosed with major depressive episode, with a major depressive episode, you need to have been feeling depressed, down, hopeless, not enjoying things and several other symptoms that you may or may not have, but you have a cluster of a number of things that are happening all at the same time.

Most of the day, nearly every day, for two weeks in a row.

So that's one way to think of it as being different, is that it isn't just one bad day, it's a bad two weeks, and it's a really bad two weeks with a lot of symptoms that cluster together.

And the second way of thinking about it is that depression, very often, not always, but very often is not because of something.

So I have, I take this for granted that this is something that people know, and then I realize sometimes having a conversation with a person who isn't in psychiatry and isn't in medicine, they ask, well, why is that person depressed?

And shouldn't you get at the reason why, like what happened in their life?

What did they do?

What are they doing wrong?

And it's not like that.

I'm smiling because they're missing the whole point.

That's like saying you have asthma.

Did you have a bad childhood or have a bad day?

I have asthma.

Did you purposefully go someplace where there were smokers?

I mean, yes.

It's a reasonable analogy.

People think about brains as being more controllable than they really are.

And we can understand why.

Your brain is you.

Your brain is your thoughts, your personality.

It is your memories and therefore your identity of how you define yourself.

But your brain is also a physical organ in your body.

And things can happen to your brain, just like things can happen to your heart, and things can happen to your lungs, and things can happen to your liver.

And just like we don't choose, I mean, we might do some things that are risky here and there, but for the most part, we don't choose to have liver disease, or kidney disease, or heart disease.

People don't choose to have depression.

They don't have depression because they did something wrong, or they're not doing something right.

And sometimes there are triggers where something bad happens, and then a person falls into a depression, but just as often they are not.

I like the example of the kidney problem, because that will lead into our first treatment here.

If, say, you went to the doctor because something's wrong with your kidneys.

Well, first they're going to diagnose you properly.

That's a big, do I need a transplant, or can I just take some medicine?

So you could take some medicine.

I'm just making this up, by the way, doctor says to give you even an idea, you get diagnosed, it's a real thing, and then treatment options.

So the first one is a big long-term trans-cranial, which is the skull or the brain?

Trans, through, cranial, cranium, like skull, so through the skull.

And then magnetic stimulation, which actually I think I had that done one time.

They put an op for depression, just the brain mapping.

I had the electrodes put on my head just to map it, but I did not have the whatever.

I was not treated.

So tell me what the stimulation is, how it works, walk me through.

If assuming people are diagnosed that they should do this one, what it looks like.

Yeah.

And I want to just address that diagnosis bit because it's so important.

There is often a notion that when you go to a doctor, just like when you go to a grocery store or you go to another service that you should have an idea of what you want when you walk in the door that should go in because you know that this has a treatment and you want this treatment.

That isn't generally how physicians think about our job though.

Our job first is to figure out, well, what's actually going on?

Could it be something else?

Could it be this?

Could it be that?

What kinds of questions do we need to ask?

If there are tests, what kind of tests do we need to do?

What kind of physical things?

That would be like going to the doctor and saying, I need a kidney transplant.

I've got 50 grand saved and I'm refinancing my house.

Like, hey, slow down.

How do you know you have a kidney problem?

Right.

So knowing what it is, or what the medical profession would call it, is really important to knowing what treatments have been evaluated and are available.

And I think sometimes people miss that step, especially-

Because if you're not diagnosed properly, that's why when it doesn't work and then you feel worse, you're like, no one can help me, right?

Maybe?

Sometimes.

I think I'd like to use the example of headaches, because lots of people can connect with that.

There is a use in the world of the word migraine to mean any bad headache.

Any bad headache you have, people call it a migraine because in their minds or in our colloquial use of these terms, our use of these terms, migraine means really bad headache.

But in medical thinking, migraine is a very specific type of bad headache.

And there are other equally bad and worse headaches that have different names.

And if you don't know that you have migraine, because you haven't gone to a doctor who asks you the right questions to tell you, okay, actually, I think this is the kind of headache you have.

You might be missing out on treatment options.

That would be for a different kind of headache.

Because migraine treatment options and cluster treatment headache options and tension headaches, they have different levels of evidence of studies of different treatment options.

So assuming we get diagnosed properly?

Assuming, yes.

And we're on TMS, that's the cranial stimulation.

How does it look and feel like if you tell me I needed to come back to your office, what happens when I get the treatment?

Well, so I also want to address what you had.

I think what you had was called an EEG, because for TMS, transcranial magnetic stimulation, we don't put electrodes on the head.

So transcranial magnetic stimulation is not looking at anything happening in your brain or trying to diagnose in the way that we use it clinically.

It's used as a treatment.

So thinking about treatment for depression.

If I'm seeing a patient for depression, I'm looking at the type of depression, how long it's been going on, how severe it is, and then other aspects of the person's life and circumstances and preferences.

And almost never am I telling a person, this is the one thing I think you should do.

Sometimes in medicine that happens in other areas more often than psychiatry, like emergency surgery.

Generally speaking, areas in medicine that are not emergencies, there is more than one option.

And there is something called patient autonomy, where a doctor might, and certainly I do, and I think in psychiatry and primary care and pediatrics is really common, you think of your job as being an educator.

You figure out what's going on first, you educate the person about what you think is going on, you know, how this fits into their concept of what they thought was going on when they come in, or how it might be different.

And then presenting the options, explaining the pros and cons of this one or that one, or this other one in the context of what you know about the person from having been talking to them for the past hour or so.

So that being said, one of my questions was going to be who might benefit most out of the three treatments we're going to talk about.

Yes.

This one, TMS.

Do you want to?

Yeah.

It might be easier to do that after we've talked about all three, so we can compare.

But TMS, I think of as being a good treatment for someone who has depression.

It can be mild or moderate or severe, although I will put in a caveat here that insurance coverage will be a problem.

I have that as two bullets.

It's well tolerated.

It's quite effective, relatively speaking, well tolerated and covered by most insurance.

If you have certain checkbox criteria and each plan has different criteria.

So why I specified that with mild, moderate, severe, is there are many plans that won't cover TMS for mild depression.

But before you get too excited, people, and it's a small risk, who should not have it.

And again, you'd get diagnosed and go with your doctor to figure this out.

Since it's a magnetic stimulation, if it's something in your head like a metal plate or you have a cardiac defibrillator.

Not that, so there is a lot of information online about TMS that is well-intentioned, but also very old or a little bit hyperbolic.

My bad.

Exactly.

So there was when TMS first came out, and then 10 years later, when it first got FDA cleared for depression, there was concern at that time that because you're using a magnetic field over the head, that you might negatively impact.

It was an assumption like I just made, just like a logical assumption.

Okay.

Be careful, being cautious is valid, right?

Well, that's part of why it is important to talk to a physician because it is really hard.

It's hard for me, it's hard for people.

You've studied it a lot.

This seems to be one of your expertise, like you're an expert on this particular treatment.

There are people who have done a lot more work on TMS than I have, but for a clinical application, yes, I would say that that's true.

You know a lot about it.

Yes.

So going back, maybe taking a step back, what is TMS?

Why would you even have that thought that it could interact with devices?

Because it was a very reasonable thought at the time.

It just hasn't been shown over the years to be actually as much of a concern as people were assuming it would be early on, and it was an assumption.

It wasn't like there was data of bad stuff happening.

It was like, logically, this might be a thing.

It's your brain.

But then it turns out.

Well, the devices, I'm talking specifically, like the TMS interacting badly with implanted devices.

Certainly, if the device is implanted right there in your brain, there could be a concern.

But if it's a cardiac pacemaker or defibrillator, or if it's a vagus nerve stimulation device, or if it's a insulin pump, or if it's a device that's implanted to treat pain in your back, lots of those devices, there's not a lot of good reason, good data to be concerned.

So I wouldn't want to stay right off the bat.

Yeah, I'm back on board.

I wouldn't worry about, if it was me, I would just come to you and ask you.

I'm clearing my head now.

Yeah, my head is clear.

Head is clear.

So EMS, Transcranial Magnetic Stimulation, what it is, is it's taking magnetic fields and using those magnetic fields to change how the brain cells are firing right underneath where you're sending the magnetic fields.

So Faraday's law states that when you have electricity, electrical current like goes through a wire and you make that electricity change, like you turn it on and turn it off and turn it on and turn it off, it's called fluctuating.

That fluctuating electrical current creates a magnetic field perpendicular to the current.

So for those of you who are listening and not watching a video, I'm holding up my two hands in a figure of eight shape.

And the reason why I'm doing that is because most coils, used in transcranial magnetic stimulation, are in the shape of a figure of eight.

And you have wires that are wound in a circle on one side and wires that are wound in a circle on another side, and they're kind of overlapping in the middle.

And you're pulsing electricity through those wires.

And when you pulse the electricity through those wires, right in the middle of that figure of eight, you're generating a magnetic field.

And that magnetic field, we put the coil on the head so that the magnetic field is going down through the skull and into the brain.

Magnetic fields are round and imprecise.

So unlike with radiation, where you might hear about sending a beam in this way and a beam in this way, and then where they cross in the middle, they have a strong effect.

You can't do that with magnetic fields.

So the deeper you go and the bigger your magnetic field is and the more brain you're catching and stimulating around.

So some TMS coils are small and precise and stimulating a area on the surface of the brain that's more like the size of a quarter and getting down in the brain like the thickness of maybe three Oreo cookies.

There are, you know, other coils that are bigger and get a larger area of the surface of the brain and also go down a little bit deeper under the surface.

So the magnetic field is the point of the coil.

The whole point of the coil is to generate that magnetic field.

And then the magnetic field makes the brain cells fire more often or fire less often.

Oh, so how does...

So it's a response.

Say that again?

Is it a response?

What makes your...

So your body, your nervous system, is it because your body's electric?

Yeah, yeah.

Good question.

So brain cells and nerve cells are called neurons, and they're called neurons in the brain, in the head, and they're called neurons in the body as well.

And if you're interested, I have a stuffed neuron right over there.

I'll paint the picture to people watching, sure.

Okay, all right.

This is a neuron that lives on my shelf in my office.

It looks like a circle with a bunch of tentacles and a big long tail, like a picture in biology, a nerve cell.

So you can think of it like a head, and next to the head, there's these hairs coming out, and those hairs receive signals from other nerve cells, from other neurons.

And so then there's this long piece called the axon, and that is where the neuron sends its own electrical signal down its body.

This is the tail now, people.

The long tail, the tail on the animal is the, is what we call that again?

Axon.

Axon.

And then there's lots of little pieces at the end that you can think of like some tentacles or, yeah.

And those send signals to other cells.

So receiving on the top of the head, where the hair is.

And passing it on to others through the tail, through more hair or more tentacle.

So the nervous system is both chemical and electrical.

The chemical is the chemicals drift across from one neuron to another across a tiny little space.

Kind of like shampoo in your hair?

No chemical?

Because you got your hands on the hair on the head of the...

I would say more like sprinkling salt.

Yeah.

So the chemicals between the neurons cross something called the synaptic cleft.

So there's chemical signaling between the neurons.

But along the length of a neuron, this is an electrical signal.

So an axon on a neuron is kind of like an electrical wire.

And neurons, there are some neurons where this axon is really, really long, like going all the way down your back.

I mean, it's still a cell, so it's, you know, it's tiny in width, but it's really long.

The electricity flows through it, is flowing through it.

Yeah.

And then in your brain, there's many, many, many, many, many, many neurons.

And some of them have really short axons and some of them have longer ones.

So there is a lot of ways that you can stimulate the brain or change the behavior.

You mentioned that you're using electric coils to create a magnetic field.

Yes.

And then that would induce, it goes the other way too.

If this is how electricity is made at a power dam, they take a magnet and they literally, the water or the electric power that they're generating the steam or wherever they're getting their power, it basically forces the magnet to spin around the wire, and electricity is magically created in the wire.

This is something Einstein, nobody in the universe, I don't care how smart they are, knows why it just is.

And so you have the reverse, right?

Correct me if I'm wrong, Dr.

You're using electricity to create a magnetic field in these cells.

It's doing backward, that's causing electricity to be generated in them.

That's exactly right.

So drugs, when you take an antidepressant drug, say Prozaxolol, something like that, those medications, those drugs are affecting the chemical signaling between your brain cells, between your neurons.

TMS, transcranial magnetic stimulation, is affecting the electrical signaling along the cells.

Oh, that explains one of my questions.

It was going to be, what's the difference between that and treatments like Prozac or Zoloft or a drug?

So there's two ways that you can do this, and this is the other way.

Well, there's many ways to affect how the nervous system functions.

For yes, so the main way that I would say TMS is different than medications, is you're trying to get at the same problem with using the electrical properties of the brain.

I'm on board now.

I understand it anyhow.

So you're inducing, you're really making those guys active, those cells.

You're getting them to stop.

Or less active.

And this is something that I think would be, it's I think too difficult to kind of go into in terms of like the details.

Just suffice it to say that depending upon how you send the pulses through the coil, you can make the area underneath the coil either more active or less active.

And does the technology get a response from the cells of your body to know which one to do?

Or you just get the treatment and you see how it works?

So your question was, do you see a response in the brain cells, or are you looking more for a clinical response, like a person's depression to change?

I'm picturing I'm a cell, because I am, this is my body you're working on.

The little pieces inside me, they feel this, they get a current.

Then what are they supposed to do with that?

Like if I'm depressed, how is it supposed to help me?

And you said it goes both ways, like you decrease it or increase it.

So I'm just picturing, I don't know what's going on.

I'm a little cell.

How does it, how does it, how does that, the next part work?

Well, neurons that fire together, wire together.

And this is how learning works in the brain.

If you do the same thing over and over, then the connections in the cells in the brain that are making you do that thing or that you are using to do that thing, those connections become stronger and stronger.

So if you're learning a piano piece, for example, the more times you play that piano piece, the more times you are using the particular neurons in the motor coordination areas and the auditory areas in your brain to do that activity to generate that piece.

And as those connections get stronger, just like as your fingers get more stronger, the connections in your brain that are making that piece get stronger.

You remember the piece better, you play it better, it becomes easier.

That is the essence of what happens when a brain is doing anything that changes it.

So making a new memory or learning a new task.

What we're doing with TMS is we're trying to get those brain cells to form connections and make those connections stronger and stickier.

With the rest of the team, the rest of the cells.

Instead of being off on my own, it's kind of like just making them all work, because there's a lot of activity going on.

We got it.

I need help.

I need to make some connections.

It's intense.

Yeah.

Or we can try and dampen the activity of that area.

And if that activity of that area underneath the coil is quieter, then its connections with other areas get weaker.

So I get how inducing electricity, you put in electricity in the cells, makes them active.

But how do you slow it down?

How do you remove?

How do you slow it down?

How do you take out power?

So the neuron has a particular way of resetting itself so that it can fire again after it fires.

And there is a way of using the pattern of pulses that we're putting through the coil.

So sometimes we're sending pulses through the coil very quickly.

Sometimes we're sending pulses through the coil slowly.

I think I understand.

Yeah.

Sometimes we're sending pulses through the coil in little triplet bursts that sound like...

Depending on how you send the pulses through the coil, you affect what the brain underneath is doing differently.

So generally speaking, and something you say is true most of the time, of course, is not always true all the time in science, especially neuroscience.

But generally speaking, sending pulses through the coil at a fast rate will make the brain cells, the neurons underneath the coil, fire more often and form stronger connections with each other.

When you send pulses through the coil slowly...

Slows them down?

It makes it less likely for those neurons to fire and makes them therefore have weaker connections with their neighbors and just be less likely to...

It's like they're building rapport.

Like if you start speaking really slow, or if you're kind and adaptable, you know, if I'm going really fast and high and wiry, I bring into that high energy too.

Something like that.

I think you could think about it like that as having an influence on your neighbors.

Like if you're chill, they all hopefully the people around you chill down, chill out, sorry, calm down, chill out.

If you are amped hyper energetic, then you can spread that energy to other people.

I think that's a very reasonable amount.

I think I'm getting clear on how this sounds cool.

So the adding a layer of complexity to that, it's not just your neighbors who are right next to each other, who you can touch with your fingers or your arms.

It's neighbors who you maybe have a highway to get to quickly.

So if I were to go down the highway, three exits, and my neighbor is right next to that exit, I could influence them to, you know, taking this analogy of step-free.

And they go on their way and they pass it on, the energy or the rest of it.

Yeah, so in the brain, there are neighbors that are really close to you in the same area of the brain.

And then there are neighbors that are tightly connected to you, but not physically right next to you.

There are information highways in the brain where there's strong connection between this part of the brain and this other part of the brain.

But the two parts that are strongly connected are not physically right next to each other.

So that's what I was trying to say with getting on the highway.

Neurons or neighbors that you can reach easily, even if they're not physically right next to you, those are the ones that are influenced by what you're going through with TMS.

If you're a neuron, if you're a brain cell, yes.

And how is it different from the next treatment we're going to talk about, which is electroconvulsive therapy?

So electroconvulsive therapy or ECT, first of all, it works in more people.

So I just want to start with that because the way treatments generally work in this field is the more benign and easy to do it is, the lower the chances are that a person will respond.

Now, response is a yes, no.

You know, to a certain degree, you can say this person's scores on their depression questionnaire, either they decreased by a certain amount or they didn't.

And that's how these things are thought about when clinical trials are being done.

And we're getting this data like, well, how many people respond to this treatment?

How many people does their depression get really very much better?

How many people does their depression pretty much go away?

And with TMS, Transcranial Magnetic Stimulation, that we were just talking about, the chances of response for most TMS protocols, most places you go, most TMS that you will get if you go to a local TMS clinic near you, your chances of responding or a person's chances of responding, about 60 percent.

So that means out of 10 people who get TMS, six will have a meaningful improvement.

And about half of that, or three out of 10 approximately, will have their depression go away.

Not go away forever, but go away for that episode, right?

When it comes to ECT, those numbers are a lot higher.

So electric convulsive therapy, we expect eight out of 10 people to have a significant improvement, a meaningful improvement in their depression.

And about half of that, to have their depression get so much better that it's pretty well gone for that episode.

And why don't we just, if I'm seeking treatment, and I'm not trying to tell my doctor what to do, but I'm like, I've heard of this treatment.

Why don't I just skip to that?

Tell me why not just jump to that if the odds are better for working.

Right, yeah.

So some people do.

So some people hear the comparisons between TMS and ECT and other treatments, and they say, you know, I just want to do the thing that's most likely to work.

And that's a very respectable viewpoint.

Most people are wanting to look at the pros and cons and the side effects and figure out what makes sense in terms of the balance of the good and the bad.

With TMS, there is very little bad.

There is the schedule.

So with transcranio-magnetic stimulation, which we were just talking about, a normal protocol used for depression to treat people would be coming in once a day, five days a week for six weeks in a row.

So that's a rough schedule in terms of just coming to the clinic.

That's like learning the piano, like you mentioned.

We're practicing.

The brain's got to practice five days a week.

Yeah.

The more you practice, the better you'll get.

Exactly.

And actually that's being shown to be true with new data coming out that with TMS seems to be more.

The more treatments you get, the more people end up responding.

So if we did 60 treatments for everyone instead of 30, we would have more than six out of 10 people responding.

So going back to ECT though, electroconvulsive therapy, it's a much bigger deal to do in terms of each treatment.

So a treatment instead of being done at an outpatient clinic, sitting in a chair awake with a coil touching your head, you are going into a hospital, into a treatment room where you are getting put under anesthesia.

And you're only under anesthesia for about 10 minutes.

It's as brief as any procedure under anesthesia gets.

Really, it's still going into a hospital and going under full anesthesia briefly.

What ECT is, what electroconvulsive therapy is, it's giving a person a seizure for therapeutic purposes.

Sounds like a reboot, like a reset on my computer.

That is how many people think of it.

We know a whole lot about what happens to the brain with ECT and after ECT.

We know which of those things might be important and which of those things might be less important.

But people say a lot, well, we don't know how ECT works.

I think that that's both true and not true.

And it's also for many things in medicine, both true and not true.

There's a limit to what we understand about the human body and particularly the brain being the most complicated, and in my opinion, the most interesting, but also the most complicated organ in the body.

So, when a person has an electric convulsive therapy treatment, we are giving their brain a seizure.

The seizure is not very long.

We're talking like a 30-second seizure, and generally, if it goes to two minutes, we'll stop it with a medicine.

And the brain is seizing, but the body is not because the person is under anesthesia.

So we have a medication that we give people to make them asleep, right?

That's what people think of as anesthesia, but also another medicine to make it so that their body doesn't move during the treatment.

So watching ECT is actually very, very boring.

You're watching somebody go under anesthesia, and then a doctor goes and stands next to their head and holds electrodes against their head after putting the dose for the treatment in the machine by turning some knobs and then pushing a button.

It's like a defibrillator, like if you're having a heart attack.

Well, analogous.

But a defibrillator, you see in the medical dramas, everybody dramatically going clear and then stepping back, holding their hands off.

The amount of energy that gets sent out of a defibrillator is enormous compared to what's used for electric convulsive therapy.

So for ECT, the amount of energy that we use at our maximum dose of ECT, which is 576 millicolons, but our maximum dose would power a 60-watt light bulb for less than two seconds.

So it's a very small amount of electricity that it actually takes to start a seizure, way, way less than defibrillator.

But same idea, right?

You're sending an electrical current through an organ to make the organ behave differently.

So in the case of a defibrillator, you're doing that with the heart.

In the case of ECT, you're doing that with the brain.

And what's the side effect or the risk that it sounds like?

Just telling me I'd have to be put to sleep and you're going to really reboot me starts to make me a little concerned.

Is it just my concern that I need to worry about?

Is there a possible side effects or negative?

There are, of course, side effects because if there weren't, then everyone who had severe depression would just go for ECT.

And that's more likely to work, right?

This is the trade-off in depression treatment.

The easier something is to do, generally for what we have now, there's always a chance that new things could come out, right?

But in interventional psychiatry, the easier thing is to do.

That's too easy, too good to be true.

It's less likely to work as well as the harder thing.

Too good to be true.

That's not, that's maybe that.

Not, not always, but yeah.

Well, I think about ECT as being for a person whose depression is so bad that they're not functioning in life or that they don't want to be alive anymore, or that their depression is really, really bad and for one reason or another, they can't do some of the treatments that are easier to do.

And that happens in my region when people live on islands and they need to take a ferry to come in.

They can't do the five days a week.

Yeah, really hard, really hard to do the five days a week for 30 treatments for six weeks in a row for TMS, for transcranial magnetic stimulation.

But ECT is doable because a standard ECT course is three days a week for 12 to 15 treatments.

So that's a lot less in terms of time burden.

So each treatment, those longer.

You should expect to be in the hospital for about two hours from walking in to walking out.

And the side effects you can get, some of them are because of the medicines that we give in order to put a person to sleep and also to make their body not shake, not move.

That's what crossed my mind, actually, when you tell me that a couple times a week for 12 weeks versus 30 still.

That's the first thing I thought, if I'm going, I'm literally, you're gonna knock me out a lot.

So with ECT though, the one where we have you go under anesthesia, that's fewer, right?

That's 12 to 15 treatments for an intensive course.

Transcranial magnetic stimulation or TMS is 30.

I may have answered one of my own questions though, which is, I was thinking at first, the convulsive therapy is more intense and I'm asleep.

And I was going to ask, when I wake up, will I just be out of my depression, feel great?

But it sounds like, no, I'd have drugs from being put to sleep and it will take a few treatments, so it's not that immediate.

Or is it?

Yeah.

Well, let me walk you through it, because you asked about side effects, and I want to make sure we do get to that.

So the medicine that we give to have a person go to sleep, that one can cause nausea.

We have a medicine to make the person not move.

That can cause, ironically, but that can cause muscle aches afterwards.

Sometimes people think they got the muscle aches because they were moving, but actually it's the opposite.

It's the drug that we give that can do that.

A person can get jaw pain.

There is a theoretical risk of hurting the teeth because you do clench your jaw during the treatment.

We put in a bite block to protect teeth, and that works.

I mean, tooth damage in ECT is extraordinarily rare.

We also can see people having the experience of being kind of out of it or waking up a little bit upset after a treatment.

That is also not very common, and we have some ways of helping a person wake up more slowly.

So those are some things that can happen around the procedure on the day.

Then there's the memory issues, the cognitive memory issues, and those are real to a certain degree.

They get very much exaggerated in media presentations of ECT, of electroconvulsive therapy.

But kernel of truth, during an ECT course, when you're coming in three times a week for 12 to 15 treatments, your ability to form new memories during that period is not great.

And first of all, if you put me to sleep that many times, it's like going to surgery, you don't remember the surgery.

I'm sure it would confuse my brain.

It's not just that though.

It is actually the seizures.

It's actually the treatment itself.

But yeah, I mean, good point.

Going under anesthesia over and over, yes.

And the treatment itself.

So with ECT, the more treatments you do close together, the more of this kind of memory issue side effect you get.

And it's temporary.

So your ability to learn new things and to remember things has been shown in many studies looking at this over and over and over where you do testing about people's ability to learn and their memory.

And after ECT, a person's memory ability to learn gets back to what was before ECT or even better if their depression improves because depression is not great for your memory either.

What I was about to say, the one thought I had is maybe why this works, but I have no idea.

I'm just making stuff up.

Is if memories, you jump in doctor from on the right track or completely the wrong.

It seems like bad memories, traumatic memories would be a cause for depression, especially if you keep thinking about it.

So if you get it wiped from your memory, you can literally start over.

Well, if only it worked that way.

We can't choose what things people forget.

And generally speaking, it's more recent stuff, like what happened yesterday or last week, or sometimes two, three months ago that gets forgotten, not something that's from, that's a traumatic memory from a long time ago.

And I just want to pause it.

So that's not the method, how it works is an idea I had, but that doesn't sound like it's.

Well, I think it's a very, based upon where you're coming from, I think it's a very logical track of reasoning.

So I want to just say something that I use to explain this to patients a lot, which is that your brain, most of what it does is forget with memory.

So it's much easier to remember, for example, what you had for breakfast this morning, than what you had for breakfast two days ago or two weeks ago.

And that's because most of what happens in your life, most of what you do, your brain deems it at some point, whether it's during the day or when you sleep at night, that's when a lot of this stuff happens, deems it not worth remembering.

You know, the interesting thing about that is it completely wipes what I just said is my theory.

And it more, my next thought, tell me your opinion.

Love to hear what you think about this idea, how it works.

It's not anything, it's very little to do with memories than depression.

It's all chemical or electrical.

Very, that's our thing about it's asthma.

And you think, oh, I had a bad day, you know, bad memory has nothing to do with that.

It's just your body, it's chemistry, electric.

So, so going back a second, what most of what the brain does is forget.

So right, it's easier to remember what you had for breakfast this morning than what you had for breakfast a week ago or two weeks ago.

Because most of the time, your brain is sorting through what happened and determining that these things are worth really hanging on to or what's called consolidating.

And most everything is considered not worth hanging on to.

What memories get hung on to and consolidated are things that seem very important, that have a strong emotion associated with them, or where you think about it a lot, and you're like, this is important.

So it's easy to remember, for example, losing a really important chess match, or winning an award, or having a surprise birthday party, than it is to remember how you got to school every morning in middle school.

Even though you did it hundreds of times, it was very not memorable, maybe.

So the way that we trust our brains, we trust our brains to hang on to the things that are important.

We don't have to try.

That's just how it works.

With ECT, with electroconvulsive therapy, your brain isn't hanging on to things in the way you would normally expect it to.

So it's you're forgetting, but also it's the normal process of forgetting.

I think I understand now.

Yeah.

Got it.

Yeah.

Right.

And so things that have happened recently, so things that have happened in the past few months before ECT are vulnerable to being forgotten.

And then during the course of ECT, your brain isn't choosing correctly or adequately what things to hang on to.

So more stuff is just not being remembered.

And then after ECT, this problem resolves.

You don't remember things you forgot because those are gone.

But your ability to learn new things going forward, your ability for your memory to work, in terms of you can trust that you are remembering the important stuff from a week ago or two weeks ago to the degree you ever were, right?

None of us are perfect in that regard.

ECT, over and over in many studies where cognition, thinking and memory is tested before and during and after ECT, that's pretty solid.

What we know is a problem that is very hard to study, actually, is that sometimes people will forget things from a few months, two months, three months, six months before ECT, and sometimes those memories seem to kind of reform or come back.

Sometimes they don't.

We think that we know that people tend to forget things that didn't happen to them more than things that did, and they tend to forget things that are more recent rather than things that are older.

But this is something that varies a lot from person to person.

I've had some patients get ECT where they have essentially no memory loss and they're fine, and I have some where they're disappointed or upset that they forgot a vacation they took six, seven months ago.

What did they feel?

Did the depression go away?

Because if it did, maybe it was worth it.

Right.

That's the crux of the issue is what's worth it to people that varies on the person, right?

I cannot, as a doctor, tell you-

How bad they feel, which you can't really get in your head to that extent.

Exactly.

So my job, a doctor's job in this situation, in this field is to explain the pros and cons.

Now that said, there are some people where I would advocate pretty strongly that they should consider ECT.

A person who's really severely depressed, it's lasted a really long time.

They've tried a lot of other things that haven't worked.

A person with acuity of their depression is high, and they are not functioning.

Maybe they're not eating well, maybe they're thinking about killing themselves.

I mean, there are-

Suicidal, high suicide risk.

Right.

Where ECT, you wouldn't want to mess around with something that has a lower chance of working where it seems more urgent.

You need something urgent, yeah.

So do you want to talk about the last item, the ketamine?

Yeah.

Yeah.

So ketamine is a drug that's been around for a really long time.

It's been around since the 60s, and it is a drug that we use for anesthesia.

It's a drug that we use to have somebody go to sleep for a procedure.

And that's what it has been used for for most of the time that it's been around.

At a certain point, it also got recognized as being a decent, not excellent, but decent pain medication.

And it also got recognized for its antidepressant effects, so for lifting mood.

And that data has been coming out now for, I would say, 25 years-ish.

But the movement towards ketamine being available as a treatment for depression, as clinically available.

It's also a schedule 3 controlled substance, right?

It is a controlled substance, yeah.

Which is why it's not, is if you're listening and you're like, well, why isn't it sounds like to just takes a prescription and like a normal drug and it's a controlled substance.

Well, and it's efficacy or not efficacy, I would say, but its ability to be absorbed and therefore for you to get enough of it to have a benefit.

If you're taking it like swallowing it like a pill, it's pretty bad.

So different chemicals in the body get into our body in ways that are better and worse.

And some things you can get injected and some things you can sniff and some things you can swallow.

Ketamine, it works a whole lot better when it's as IV.

So going from a drip straight into your vein.

It works in terms of absorption decently well.

If you're sniffing it, it's called intranasal, kind of like how some people take allergy medications, right, going up each notch.

Which can become addictive, right?

The nasal spray.

So there isn't anything more addictive about the nasal spray than about ketamine in any other form.

Okay.

That's another myth.

That's not read on the Internet, and you got to be careful about that.

Ketamine is the same compound, whether you're getting it in your vein or getting it orally or sniffing it, which is called intranasal.

With one exception, the FDA approved version of ketamine called esketamine is a little bit chemically different.

Esketamine is delivered intranasally, but it being chemically different and it being delivered intranasally have nothing to do with each other at all.

So it was two different decisions that the drug company made.

One was to do something slightly chemically different than the ketamine that's been around for decades.

And the other decision was to make it intranasal so that it would be easier for people to use for clinics to offer.

So ketamine, it's a treatment for depression.

It's also a treatment for pain.

It's also a medication for people to go to sleep for surgery.

I've seen it referred to as like a horse tranquilizer.

Well, if it's a horse tranquilizer, it's also people tranquilizer.

I mean, we use it a lot in human procedures too.

So I thought that it's a very interesting thing that I see online pretty regularly.

Ketamine for all intents and purposes is a drug for depression, therefore an antidepressant.

Why it gets so much attention as being something kind of different than the oral drugs you would take at home is because it's on the newer side.

It was approved by the FDA for treatment for depression in 2019, so it's still very new.

The use of ketamine before that in off-label, non-FDA approved formulations, that was something that was happening when I was in residency and fellowship.

It was just kicking off, so we're talking around the early 2010s or the few years before that.

So new and exciting.

How does it work?

Because I'm going back to, you gave a great explanation of all the electrical treatments, and those sound kind of effective or somewhat.

This is the chemical one.

Earlier, you were telling us the cell, it can be affected chemically or electrically.

This is the chemical one.

Do we know how it works?

We do and we don't.

So we know various things that ketamine does to cells and does to the chemical transition to those chemical signals between cells that are happening at what's called the synapse, the little gap between one cell and another.

We are not entirely sure which of the things it does is the most important.

And I think there needs to be a big note of caution with that because there was this, I would say, very bad publicity that happened a few years ago around selective serotonin reuptake inhibitors.

So the Prozacs, the Zolofts, Selexes of the world, where the public was told over years by drug companies that the way SSRIs worked were this very simple thing that we could do with an animation and a brief ad.

And it turns out that that isn't really how they work.

Doctors, medical professionals, have known that for a really long time, that things are complicated and this overly simplistic way of explaining it was probably not true, or even if it was true, it was only very partially true.

And it's an ad on television, so try to sell you something, yeah.

Really simple.

Nothing is actually simple, I would say, in medicine, in neurobiology.

So what I'll say about how ketamine works is that it affects the same circuits and chemicals that are involved in depression, it just gets at them a different way.

So there are chemicals that we know are involved in depression and they're involved differently and in different parts of the brain.

But the ones you might have heard of, dopamine, serotonin, norepinephrine, there's also which are less commonly known, GABA and...

So would I be...

So fix what I'm going to say next or tell me to edit it.

Would it be fair to say we know it works because we were using it as a drug for anesthesia and other purposes?

I think EMTs carry it, right?

And although people report it worked for depression, so we started using it.

And back to your concern about it because we don't really know how it works.

So let's slow down a little bit, be careful till we learn the chemistry better.

So let me take that piece by piece.

Okay.

So a couple of things.

First of all, when we see something work by accident, we don't make in the scientific world, in the medical world, we don't make any conclusions about causality, or about whether what we're seeing is real, or about whether that's something that is going to still be true once we look at it more closely.

So there are stages of getting something from an initial idea, and we see it once or twice, and wow, this is cool.

That's called anecdotal evidence, meaning someone tells a story about how cool it is or interesting it is.

Anecdotal evidence is considered the lowest level of evidence.

I don't like anecdotal evidence myself, because it's like you could pick anecdotal evidence, like, oh, the sun is out, so that's why I'm not depressed.

Well, no, I mean, it's nice to see sunlight or pick anything.

That's a casual causation in bad science.

The thing is, you can't experiment with people, unlike I could experiment with a rocket, and if it crashes...

We can, but we can't, actually.

So that's where, when you have an idea and you see something interesting, the next step is to figure out how to look at it in a way where you can see this connection, I thought I saw, that might just be a correlation.

Correlation means two things go together, but they don't necessarily cause one another or have anything to do with one another.

So I actually want to pause there and talk about correlation and causation because it's like a really important concept.

When I first learned correlation and causation, when I was in, I think, late high school or early college, the example that was given to the class is that the more priests there are in an area, the more strip clubs there are in an area.

And the class was asked to explain that.

And people came up with, well, gosh, I mean, if you have strip clubs, then people feel guilty, and maybe they want to go see priests.

Or if they see priests, then they might feel rebellious, and that's why there's more strip clubs.

But actually, there's this third factor that connects the both of them, which is population size.

And so the two things really are correlated, but they have nothing to do with each other, because what actually causes both, more priests in an area and more strip clubs in an area is the size of the population.

So Bend, Oregon has fewer priests and fewer strip clubs than New York City, right?

That's something that I think is hard for our brains to do.

And it takes effort and it takes reminding, thinking scientifically, thinking that something we see that goes together might not actually be a real causation.

Our brains don't naturally really work like that.

We have to work hard to step back and say, wait, wait, wait, we need to actually look at this.

Do you somehow get to actually do this in your studies?

Right.

So there were many, many stages between what you described of, we saw this thing happening where ketamine seemed to improve mood and getting to the point where we're thinking about using ketamine to treat patients.

And those stages are our clinical trials.

So smaller ones at first, then bigger ones, more robust ones.

And what we're doing is trying to systematically look at, if you hold everything the same, as much as you possibly can.

And the one thing you vary is the person got the ketamine or didn't get the ketamine, and they don't know which one they got.

You still see a difference.

So you try and take away all the factors and see if there's a causal connection.

How far along are you on that kind of research?

Well, when it comes to ketamine and S-ketamine, we're actually pretty far along.

So ketamine has a pretty solid evidence base from many different studies, from many different settings of varying size.

S-ketamine, the drug that got FDA approved in 2019, that drug had a very large clinical trial, actually several very large clinical trials that were done by the drug company over the few years before the approval.

And then there's been data collected since then.

Those trials that are done by drug companies, people sometimes think of drug companies as the villains or the bad guy.

I think that that's not the case generally in our medical.

It's a conflict of interest because someone has to do it, they have to do it, they have the drugs, but it's also to sell them.

And they don't want to be too dishonest because then it will hurt if they hurt someone.

We're going to go, now you didn't, you didn't be forthcoming conflict of interest.

It's in a way like that.

And it's in a way, it's even more complicated where the kind of data that the FDA needs and requires in order to approve a new treatment, it's so hard to do and so expensive to do and takes such size and rigor and oversight that most universities settings can't do a trial like that.

So when we get new medication out into the world, that has been through that process, it was very, very difficult.

So drug trials are really, really hard, really well regulated, and really rigorous.

So if the ketamine is at a point where it's, you understand it, we're not back in the anecdotal of that work, let's use that.

You really, it's safe, or you understand how safe it is, and what it does, what...

Well, and I want to also divide that up.

Knowing that something works, and having really good data that it works, that it's safe, that you have good durability, or you don't, that is all different than knowing how it works.

And people equate those two things.

Like, if you don't know how, then it doesn't work.

Not exactly true.

So lots of things in medicine, drugs in particular, I will say, we know they work because there's really good data from really well-done clinical trials.

And then when it comes to how, there's still some ambiguity.

It's unclear.

So you obviously have some guess or some idea because you wouldn't get a compound all the way from being thought of and created to being evaluated in humans without some idea of thinking about, well, logically, why would that, why wouldn't we expect this compound to do this thing?

So we could, I mean, though, I think we said earlier we're not really crystal clear on how it works.

Yes.

But we know it's clearly we've done enough that it does work and we can use it.

Yes.

When would I do that instead of the first treatment, the electric treatments?

Of the TMS.

So we're on-

TMS, the brain stimulation, not the intense one where you put me under and shock me, the one I go in five days a week just for magnetic stimulation.

Right.

What do I choose ketamine over that?

Because I don't want any stimulation on my brain.

I just want to do the drip.

You are looking at very similar people in similar circumstances with similar levels and types of depression who are thinking about both of these treatments.

It's actually a very good question.

So who would think about TMS, transcranial magnetic stimulation, and who would think about ketamine, whether it's ketamine or S-ketamine?

Those are very similar people.

So I wouldn't say that there are aspects of the depression, the symptoms of depression that would really distinguish who should go one way or another.

I wish there were, and maybe there will be at some point in the future or near future, maybe.

But right now, if a person is deciding between TMS and ketamine as ketamine, they're looking at first of all, durability, and second, convenience logistics.

So TMS has better durability after the intensive course.

You do your 30 treatments, you do a little taper, and then your chances of staying well are pretty good.

So you don't need to come back in over and over and over for TMS treatments when you're feeling well.

Some people do that.

There are circumstances where that is done.

But generally speaking, most of the time, most people getting a course of TMS, they do the course, they stop, and they only come back in if they're feeling bad or if their depression comes back.

So the durability is pretty good.

So people who respond, then they stay well better than with, say, esketamine, where if a person's coming in for an intensive course, the intensive course is easier.

So an esketamine course is twice a week for four weeks in a row.

So it's eight treatments.

And if you do well with that, though, you don't just stop and come back if you're feeling bad.

You need to come back in again once a week for four weeks in a row, and then come in every other week indefinitely.

These are IVs.

So you're putting a needle in my arm?

No.

Esketamine is the...

Oh, that's the nasal?

Yeah.

That's the SKA cleared medicine that is also intranasal.

Yeah.

So esketamine, you're coming in like every other week in order to maintain the benefit.

So which one of those appeals to you?

What can you do logistically?

What is your insurance cover better?

Often comes into it.

I wish it didn't, but it does.

And if it's just a nasal, is this the nasal spray?

Esketamine is a nasal spray, yes.

Then how come I can't take it home and do it?

Because the government will not allow you to do that.

Okay, simple answer.

Yeah.

Yeah, it gets very confusing, very fast, because generic ketamine is actually less well regulated than the FDA cleared esketamine.

But the FDA approved, actually, the FDA approved esketamine.

The requirement for administration is that you take it in a physician's office under observation and then you hang out for two hours after you take the medication.

And then at the end of two hours, if you're feeling well, if your blood pressure spiked, it must be back to normal and then you can go.

That is something that I think regulatory wise is a bit overkill.

However, when a person is getting esketamine, those are the parameters that everyone is working in, your doctor, you, right?

And that's the regulatory requirement.

Okay, great.

Is there anything else you want to talk about in terms of the three treatments until I ask you, how you got to be a doctor?

Part of what I do is about coaching people.

Do the dream, do what you want to do.

I have you want to talk about depression because you can't help people with that.

And if they've got that, they need someone like you to help them.

So how did you get to be doing what you're doing?

And tell me about your clinic, the Seattle NTC.

Well, when I was growing up, I became very interested in the brain at a young age because my grandmother had a stroke and that was sad and a loss.

And she lived for another decade or so after she had her stroke.

And the person I got to know the best growing up, the one who I remember the most is my grandmother, who'd already had the stroke.

And she had some deficits, some changes in her brain from the stroke that were very interesting and hard to sort of wrap your mind around, like, well, why would the brain work like that?

One of them was the most basic one that she had her stroke on the left side of her brain and the right side of her body became paralyzed.

She couldn't move her right arm or her right leg or the right side of her face.

And I thought as a kid, that was just really strange.

I think she was, I think I was about six years old when she had the stroke-ish.

And then she also had some speech issues called aphasia.

And her particular type of aphasia was just very interesting to understand.

Well, how could that be?

If I said a word to her, she could repeat the word right away.

Any word I said to her, she could repeat it back.

And you were six or seven years old.

Yeah.

And give her a whole sentence, though, and she couldn't say it back.

And she also couldn't think of those words herself.

So she couldn't generate words.

She had like a limited set of words that she could say, like, my, my goodness sake.

She would say yes and no, but sometimes she wouldn't get those right.

She did have some swear words in there, and I didn't know that until I was a teenager.

She did actually know enough of what she was saying to like not use those around me.

So this notion that she could understand what we said, but she couldn't find words and generate them.

But then she could repeat words she just heard.

That to me was like, wow, the brain must be just really crazy and weird and interesting.

So when I was a teenager, I started reading some of the sort of pop psych books about the brain.

Like, how does the brain work?

And the ones by Oliver Sacks, who was a neurologist who wrote about like really interesting patients he had.

His most famous book was The Man Who Mistook His Wife for a Hat.

So I read those books and became very interested.

And so when I went into college at Stanford, I thought, you know, I'm going to go in and I'm going to become a neurosurgeon or a neurologist.

And then it turns out that me and organic chemistry are not an excellent match.

So I didn't do well on an organic chemistry quiz.

And I went to my teacher and I asked, is there tutoring?

Is there anything available?

And he said, you know, too many people want to be doctors.

Maybe you should like consider doing something else, consider not being a doctor.

And so I became a psychology major, which I loved being a psychology major, was fantastic in terms of really learning scientific method.

Like, how do you answer a very difficult question by generating an experiment and design that will really remove all the other factors and you can just compare two things?

And psychologists think about that more than anyone because it's the hardest thing to do is doing psychology studies.

So then I got to the end of college and I had this psychology degree and I was looking at all the different options and I was like, shoot, the one that looks the best is still medical school.

Darn it.

So I took a year and I did some of the pre-med classes that I had not done as an undergrad and then applied to medical school and went to medical school.

There I struggled a little bit to choose a specialty, but I was only choosing between two, I was choosing between neurology and psychiatry because it was going to be the brain, no matter what, it was going to be the brain.

And I also struggled with, well, do I want to be a researcher, or do I want to be a clinician, or do I want to try and do both?

Do I want to be academic?

Do I not?

And you don't have to make all those decisions in medical school, but I did get a research degree in there, I did an extra year.

Oh, you're remembering your grandmother this whole time.

Is she your motivation?

Like, if only I knew or someone knew they could have made her better again?

Well, yes, I think we're still not there, though.

There wasn't anything that somebody could have known then that we know now that would have changed that out.

You know, we wish, like in the 90s, when I spent a summer working in a neurosurgeon's lab, you know, working with cells and looking at cellular regrowth of neurons, I had this hope that, you know, by 2024, there would be some way to repair brains that have been hurt by a stroke or brain injury that is dramatically different than what we had in the 90s.

And that just really hasn't come to pass.

It just got to you really on the path, got you interested in the whole thing.

Yeah.

Yeah.

I mean, there are ways that her stroke could have been seen to be coming or caught a little sooner.

But after it happened, yeah, not much.

Although, there are some studies looking at stroke recovery using TMS, transcranial magnetic stimulation, to help with that.

So we talked about TMS in the context of it being a depression treatment.

But TMS is a tool, and it's what you do with the tool that makes it a treatment for this or treatment for that.

And there's a lot out there on TMS being looked at as a tool.

Yeah, sorry to tangent from your story, but I think when I introduced you, there was dementia in there.

So yeah, so when I went to medical school, I was really interested in psychiatry and neurology.

I chose to do a psychiatry residency.

I went to one of the Harvard residencies in Boston, and there I got very interested in the overlap between neurological illnesses like stroke, brain injury, dementia, and psychiatry, or the behavior and emotional changes that come along with that.

So after I did regular psychiatry residency, which is four years, I stayed in the Harvard system at the Brigham and Women's Hospital for another two years to do a fellowship in behavioral neurology and neuropsychiatry.

And you had asked me to explain before we started, you'd said we were going to like sort of talk about career trajectories a little bit, profession.

So I want to count the years up here for you just for a thought.

I was just doing that.

I was like, yeah, most people think, oh, like they think they're, I think therapist and you know, what do they have a college degree?

I mean, psychiatry is a pretty serious.

Yeah, go ahead.

It's a lot of work.

So we're talking of four years of college.

And then if I gone straight into medical school, it would have been four years of medical school.

As it was, I took two years in between because I had to do those pre-med courses and then apply.

So four years of medical school, two years off in between, right?

Four years of college, two years off in between, then four years of medical school.

And I added a year to medical school to do my master's in biostatistics and epidemiology.

So I actually was in medical school for five years and got, I had two degrees at the end, an MD and an MPH.

Then four years of residency, and then two years of fellowship.

I'm counting up to 15.

I'm counting 15, not counting the two in between.

So the minimum you can do to be a psychiatrist, the absolute bare minimum, four years college, four years medical school, and four years residency.

So that's 12 years.

That's the minimum.

In comparison, other professions, so a person who is a lawyer, for example, will have four years of college, and three years of law school, and then that's it.

And what about a therapist?

Which a lot of people go to the therapist because maybe insurance doesn't cover a psychiatrist or they don't need any referral.

But more or less-

The rules are different.

The rules are different.

So most of my patients-

How much school?

How much school does a therapist need versus a-

A therapist will have an undergraduate degree.

I don't know of any therapy pathways where you get an undergraduate or a bachelor's.

And then after that, it depends on what kind of therapist you are.

So there are social workers who are therapists, and they've gone to social work to get a master's, they've gone to school for a two year or three year after college.

There are therapists who are marriage and family therapists, and that's a shorter training.

I don't know how much shorter, but I think it's on the line of like a year, year and a half, maybe two years for marriage and family therapy, but it's shorter than social work.

And then there are on the longer end, people who have a doctorate, a PhD in psychology, or what's called a PsyD, or a psychology doctorate.

Generally speaking, the PhD is a little bit more research-oriented, the PsyD is a little bit more clinical.

And those degrees, people with those degrees can also be psychotherapists.

And then psychiatrists can be psychotherapists, but these days, usually not.

Not always, right?

So I have, yeah.

As a patient, someone who, we've all got problems, say you've got depression, most people probably see, this is a question for you.

They probably, I'm assuming, go see, recall the person in the office you're just talking to before you get to the doctor of psychiatry.

There's therapists.

A therapist?

Therapist?

Yeah.

How do you make the leap between therapist and going to some place like your Seattle clinic?

In some places, it's actually harder to get a therapist than it is to see a psychiatrist or primary care doctor or nurse.

So I do actually see a lot of people who either haven't been to a therapist in a long time or had a therapist and didn't like it and can't find another one.

So it's not always like a step-wise progression.

So when you're thinking about though, do I want to try talk therapy or do I want to try a medication?

I would encourage you to look at all the options and think of it as a both and, not a either or.

Oh, perfect.

Yes, both.

Not one or the other, yeah.

Right.

Addressing problems through multiple modalities, multiple ways of looking at it, multiple ways of treating it is usually better than thinking about.

Also, if you go to the psychiatrist and you get the brain stimulation treatment and you start to come out of your depression, you probably need a therapist, someone with the fore or the masters really to make you change your language, the way you look at things so you don't start creating bad memories and bad habits again.

I think that's reasonable.

When we have people come through a course of ECT and their depression is lifted, maybe even gone, and they've been depressed sometimes for 10, 20 years before that, it is a dramatic shift and it's a good shift.

But it's also, gosh, I don't know how to be a person who doesn't have depression.

So I agree with you.

There is a lot of role for a therapist.

I mean, the idea doesn't have to be, in fact, this is one thing that people stuck a lot of things in life.

It's do this or do that.

I'm like, you know, there's more than two options always to do both.

Or this notion that it's sort of linear, that you got to do this.

Right.

And it's just not.

So I have a lot of patients who have medical problems that contribute to their depression or worse, their depression.

You don't want to just try to treat the depression and then treat the problems.

You want to want to try and treat everything that you can fix.

Now that said, listen to your doctor on what to do and what not to with any given treatment.

So for example, with transcranial magnetic stimulation, we don't suggest people change medications during the treatment course.

Because then first of all, you don't know what worked, right?

If you're thinking about it a few years later, do I do this treatment again or not?

You don't know if it worked because you don't know whether it was the medication change or whether it was the TMS, right?

So that's problem number one.

Problem number two is there can be some issues of dosing where changing what medications your brain has on board can change how your brain reacts to the machine.

And we do dosing, we didn't talk about this much in this conversation, but we do dosing by evaluating how your brain responds to our machine, how high up we have to turn the machine in order to get a twitch in your thumb is more or less how we do it.

And the responsiveness of your brain to the machine can be different.

So it's not always do everything at once, but thinking about things as not being mutually exclusive, I think is good.

Yeah, definitely.

So your clinic is called the Seattle NTC.

It will be in the show notes.

Do people have to fly or travel to Seattle to see them?

The Seattle Neuropsychiatric Treatment Center.

And I just want to say, my reason for doing this podcast isn't to promote my clinic, because it really isn't a very reasonable option for people outside of like the, the Seattle general population area, right?

I'm sure you have listeners all over, right?

Well, so in terms of not to talk about myself too much, I don't want to even, but the mold testing like I do, I used to do, test people's houses for mold and chemicals, air quality.

And one of my clients in Santa Fe is like, you got to know this doctor in Utah.

I'm like, okay, I'll.

And so I go to Utah because I do travel around doing work for other people.

I put together road trips where people are desperate.

And I'm going to stop to see this doctrine.

I, nobody in this clinic lived in Utah.

And I'm like, why Utah?

And for whatever reason, and yeah, people come.

So it's like if you're the expert and there's, you have resources and you can't be everywhere.

People can find a way to get to you.

I just wondered if it was because, if you also had an office in Phoenix or something, or that kind of thing, but it's just the Seattle office.

Yeah.

And I want to also say there are, there are clinics that are centrally owned and that have branches all over the country.

Those clinics tend to not be owned by the doctors providing care.

I'm sure I'll say that and then somebody will think of one that is, but generally speaking, the larger organizations, healthcare organizations that have clinics all over the place are owned by investors, venture capitalists, not necessarily by the doctors providing care on the ground.

My clinic, my set of clinics, we have five.

I'm one of three owners where all three of us, physicians or psychiatrists, we have other providers with us.

But as some of the doctors in our clinics, you know, ourselves, we have a lot of investment in things going well, and we see our patients responding or not, and we see how the clinic flow is.

We are very invested in doing a really good job for our patients.

And that's different than somebody trying to run a clinic who isn't on the...

I appreciate too, appreciate you not trying to sell yourself.

The mold doctor and any people, it works, people come.

My question is, and not to get, I'm on the trap with you, don't plug yourself, you're good, people will find you.

But it's a valid question in terms of, say I am interested in your service because I know you now.

Is it okay for a psychiatrist to do a virtual assessment diagnosis before I, actually, I just thought of you have to do five days a week for months, how's that going to work?

I was thinking-

Five days a week for six weeks, if you're thinking about TMS.

Yeah.

Okay.

Well, it can be arranged.

If I was really depressed, not, my question is, are you allowed to do a pre-assessment virtual?

Do I have to come in your office?

It's a gray area.

So generally speaking, the official answer to that is no, you need to have a license to practice in any state where the patient is located.

That said, if somebody is going to be coming to you for ECT, having some kind of conversation or having some kind of exchange of information, if not with the patient themselves or with their psychiatrist or whoever is taking care of them locally, it's just good care.

You don't want somebody flying all the way, thinking they're going to get ECT.

You get there and you're like, wow, no, maybe this isn't, this treatment isn't a good match for you.

So we find ways to make it work.

But the official legal answer to that question, that a psychiatrist has to have a license, any physician has to have a license in the state where they are practicing and where they are practicing is where the patient is.

Okay.

You did give me, and I'm going to put it in the show notes for everybody, the general, you gave me some good websites for the Magnetic Stimulation Society where people can go and learn more and find somebody more local, right?

Clinical CMS Society.

I mean, and the overview of our clinics, Daniel, we are a little bit unique in that we offer, we try to offer like kind of everything in the interventional field that has good evidence, right?

Is your expertise primarily depression, even though some of those treatments can be used on other things?

Well, I would say 80 to 90 percent of what we do is treat depression.

That said, there is also a version of TMS that is for OCD.

So we have a number of patients with obsessive compulsive disorder.

There are off-label uses of TMS, meaning not approved by or cleared by the FDA, but that have good evidence base, where we will sometimes treat things that are a little bit more unusual.

And ECT, electroconvulsive therapy, which is the one where you're going into the hospital and getting a seizure, that's also used for catatonia.

It's used for bipolar disorder.

It's used for psychotic disorders sometimes too.

So we do see a breadth of different kinds of disorders.

We have an IV, so we have at our clinics, an IV ketamine program, which is the generic ketamine.

It is off-label, but because it is not the one that has the very tight requirements and the insurance requirements, we're able to be more flexible with who we treat and for what.

So we're able to look at the evidence base, look at the papers, look at the studies, and figure out what's best for a person separate from, well, what is the insurance wanting or not.

We have also the insurance covered version of ketamine, which is the S-ketamine, and that's the intranasal.

Oh, insurance, that's all, that's...

It's always a thing.

Yeah.

And we have also ketamine-assisted psychotherapy.

So we have two extremely well-trained therapists.

That's one we haven't talked about.

And I didn't ask you how much time you have, and it's almost an hour and a half, so I kind of, that's why I wanted to cover everything.

I assume you're going to cut it down, I assume.

I'm trying.

Oh, no, I'm not...

No, I mean like when you edit, right?

No, people can hit fast forward if they want to.

People, they want to need to hear this, that's why we're doing it.

That's something we didn't get into though.

If you like, if you have the time, what's the difference between the psycho-assisted therapy and just going in and doing the nose spray while they watch you because it's a regulated drug?

Well, or they're the same?

They're not the same.

But so we have the, I wanted to finish the list.

We have the ketamine, we have electric convulsive therapy, we have transcranial magnetic stimulation, and we also have patients with implanted devices called vagus nerve stimulation devices.

That is a treatment for depression.

And we also participate in clinical trials.

And one of the clinical trials we're participating in is, looking at psilocybin, which is mushrooms for depression.

And two others that we're participating in are looking at ways of doing TMS differently.

So that's sort of the breadth of what we do.

And then your question about ketamine-assisted psychotherapy.

Ketamine-assisted psychotherapy, the purpose of the drug is a bit different than when you're taking the drug as an antidepressant.

So when you're taking ketamine as an antidepressant, you're taking it like you would Prozac or like you would Selexa.

You're taking it because the drug itself is going to affect your brain in a way that makes your depression better.

That's the hope.

That's the intent.

And you don't need anything else happening for that to occur.

You just take the drug.

When you're looking at a drug-assisted psychotherapy, the goal there is to get your brain into a different state in order to process things that are harder to process when your brain is in its usual state.

So getting past some of the ingrained pathways of thinking.

Oh, is that the mix then?

You're adding the mushrooms into that?

No.

So I'm talking about ketamine still.

Okay, we're still on ketamine.

Yeah.

Although the idea is the same with mushrooms, but just to be very, very clear, ketamine is legal, and we can use it as a clinical treatment.

Mushrooms, psilocybin is not, and the only use of psilocybin in our clinic is in a trial, is in a clinical trial, is in a study.

So never the twain shall meet, they have nothing to do with each other.

But in terms of concept, you're right that it's a similar, it's a similar idea.

So when we have ketamine-assisted psychotherapy, it's a clinical treatment, it's not a research trial, it's clinical treatment.

And the idea there is they're taking the ketamine in order to feel different, like to actually get an effect that you can feel in order to be in a different place to process.

That's what I thought just, I was assuming that with everything, with everything, with the normal ketamine, you don't have as good a feeling then.

You might not.

So a lot of people's experience with ketamine, with IV ketamine, S ketamine, when you're taking it as an antidepressant, is that the dose that has good evidence of efficacy of working well in the research studies that we're basing our treatment off of, that that dose might make you feel different the first time or the first two times, but it doesn't necessarily make you feel different every time, and that also isn't the point.

And there's some pretty good data out now that, at least with S ketamine, how it makes you feel in terms of high or dissociated or not doesn't really make a difference as to whether your depression gets better or not.

So that was a question, right?

And it's a very reasonable question, like does how you feel on this drug have anything to do with whether it works?

And for S ketamine, the answer seems to be probably not.

When it comes to therapy, though, if you don't feel any different on the drug, then the point of using the drug for the therapy isn't met.

You have to have something that makes you feel different in order to have a drug-assisted psychotherapy, be different than normal psychotherapies.

So we have a therapist there instead of just a doctor.

That's the difference mainly.

When you are getting ketamine as an antidepressant, you don't have a doctor sitting with you for the two hours.

There isn't a point to that.

It's just a legal requirement and more than a therapy requirement.

No, I'm trying to figure out where you're coming from.

I'm trying to actually see myself there in the office.

Let me walk you through it.

Okay.

So let's say you are going to have S-ketamine.

First, you've met with a physician, and in our clinic, it's a 90-minute appointment.

You've talked about your symptoms, you and the physician agree that the problem is depression, you've heard about the options of treatments for depression, and for whatever the reasoning is at the end, S-ketamine ends up being the plan that you've chosen.

Okay.

So you've decided to getting S-ketamine.

Then when you come in for your first S-ketamine treatment, you are greeted by the staff member who is going to be monitoring you and taking care of you during your treatment.

You are brought into your treatment room, which at our clinics consists of a relaxing recliner and a side table and a little lamp.

And we also have, because S-ketamine can cause nausea, we have vomit bags subtly tucked under the side table.

And because it can cause a weird taste, sometimes we've got jolly ranchers.

And you also are given a button that if you push it, the staff member is notified that you want their attention.

And in some of our clinics, there are shared rooms with a divider.

So people have their own space visually, but they're still in a room with other people.

And in one of our offices, it's actually there, it's your own room.

So it just depends on what physical setup we could get at different spaces really.

And then the staff member will ask you a few questions about how you've been doing.

We'll ask you a few questions about your medications.

We'll take your blood pressure and check your heart rate.

And then we'll administer the medication, which means handing you the vial.

And you already know what dose the person is getting because the physician wrote the instructions.

Basically, the physician has prescribed this, and it's being implemented as the physician prescribed.

And the staff member will show you, demonstrate with a device that doesn't have drug in it, how to use the device to get the drug intranasally delivered.

And then you will self-administer your medication.

And then the staff member will be checking in on you periodically to see how you're doing and to check your blood pressure and your heart rate, again, a couple of times.

So your experience is mainly chilling out in a recliner.

We do not recommend that people make phone calls or send text messages or emails.

That said, we don't actively stop people.

We don't like, you know, we're going to confiscate your phone.

But we strongly recommend doing something like listening to music or, you know, if you're going to read, if your brain is going to be in a state where you can read and follow a story, having it be something that's non-distressing or doing like a mindfulness exercise, you know, with an audio, like a podcast or something.

So there is always a physician on site.

If anything, you know, happens or if you have a question, but a physician being there with you would probably be more disturbing than helpful, actually, sitting there with you the whole time.

Just bugging you?

Just bugging you, yeah, exactly.

Looked at me.

Yeah.

If you're coming in for intravenous ketamine, for IV ketamine, you are greeted by a staff member who takes you back to the IV ketamine treatment area.

You have a conversation with the nurse who asks you some questions about how you've been doing, and make sure that your vitals and everything is healthy enough for you to get treatment that day.

And then she, she in our case, our nurses can be he in our case, will put in an IV and then start the drip going for your ketamine treatment.

And the drip going into your vein, the infusion lasts 40 minutes, and then at the end of the 40 minutes, you are given as much time as you need, and usually that's another half hour, 40 minutes to chill out and to let us know when you are feeling back to your usual self.

And we're also monitoring your blood pressure during that time.

An IV ketamine in our clinic is in a shared room, so that the nurse can see everybody at the same time, but there are freestanding dividers between the chairs, so people kind of have their own their own visual face, and they're looking out a window.

Yeah, so IV ketamine, the whole experience from walking out is maybe 90 minutes.

Is there anything else we haven't covered?

I mean, there's so much, so much.

I, what I want to just leave people with is, a doctor is more like a teacher than anything else.

A consultant, a teacher.

So going and seeing a doctor, going and seeing a psychiatrist doesn't automatically mean there's something wrong with you, right?

And also, you don't necessarily know what all the options are for what you're going through.

And it's your doctor's job to know what those are and to explain them to you and teach you so that you can make good decisions about your health informed decisions, not to boss you around or tell you what to do.

So, ask questions.

It is literally, it's our job to answer questions and to make sure that people are informed about what treatments they're considering or that they're doing.

And it can't be your job as well if we don't ask you questions, right?

And I would also encourage you to seek out a doctor who is not hesitant to tell you, oh, wait, you know, I'm not sure I know the answer to that one.

Let me go look it up and get back to you.

You know, that sometimes I'll hear people say, well, that makes me nervous.

They don't know everything.

Nobody knows everything, right?

And medical knowledge is always changing month to month, year to year.

So you really should have somebody who's invested in keeping up with the latest, keeping up with the...

Or worse, though, they use chat GBT.

Ha, no.

Yeah, I had one of my guests who's a doctor in the hospital, and we were talking about AI.

And I was like, well, how do you know if they did have it, which they're not using it for something like that?

Like, does she project GBT?

Like, instead of asking Dr.

Allen, let me see if the chat GBT makes agrees with her.

No, because he's pointing out that's just based on what's available on the Internet, limited data sets, et cetera, et cetera.

And they're not supposed to be using that for that.

So you could get the wrong answer.

Well, and your doctor has the right answer.

Well, not always.

I want to say, if you're seeing a person who says, you know, I think that there's another person out there who might know more about this than I do, or might have better advice for you, it's not a rejection, right?

That's actually just the reality.

We all have different areas where we know more and we know less.

So, if you, for example, are seeing a nurse practitioner or a physician assistant, there are lots and lots of things that a nurse practitioner and a physician assistant are fabulous at, you know, knowing how to help you and knowing how to get you through it.

There are also things where the complexity is high enough, or the severity is high enough, where it would be a good idea to see a physician.

So, it's a matter of figuring out, and then within physicians, different specialties, right?

Sometimes what's going on, you really should see a sleep physician, or you should see a neurologist instead of a psychiatrist.

So, it's all about...

It's very complex, which is why...

Just to come in or talk to a doctor, and then make an opinion after you talk to the doctor, right?

Right.

But not always a doctor, right?

So, we mentioned there are nurse practitioners out there, there are physician assistants out there.

The education years is undergrad, plus generally two years of grad school.

So, there are a lot of areas in this country where accessing a physician, not just in psychiatry, but in lots of specialties is really difficult.

And the practitioners, the non-physician practitioners with these shorter education periods, so two years of grad school as opposed to four, and then not having residency, that fills a need.

I think it's really important to know who you're going to see and don't assume you need one thing or another, right?

So there are people who get kind of focused on, I have to see a doctor, not always, not for everything, right?

Or who...

Well, there's chiropractors.

You get stuck in a doctor for your back and you're a chiropractor.

Just doesn't always who you thought would be.

I mean, and I think that the term doctor is difficult because there are lots of degrees that end up with a person being called doctor.

And so it isn't saying, I want to see a doctor.

I think it really helps to know what kind because chiropractors, I think, are technically doctor.

I think it's a doctor.

They get naturopaths.

It's an ND naturopathic doctor.

Yeah.

My intention was just when you get stuck on what's going to fix me and heal me and better, there could be something you haven't thought of.

Yeah.

And the doctor might tell you chiropractor, if you go ask the doctor or not, or might say you need back surgery, but you don't know unless you talk to them.

It depends on who.

We're all people.

We all have our different things that we know more about and less about, and different thoughts.

I would say it's just important to know who you're seeing.

So look them up, write, ask questions about their background.

All of that is fine.

I do not get offended if a person asks me, so wait, you're a psychiatrist.

What does that mean again?

Where are you in your education?

I get drugs.

That's the only thing I know about psychiatrists normally.

I need them for a drug prescription.

In this case-

Where did you do your training?

When did you-

All of that should be open information.

Now, visits are only so long.

So if you spend half of it asking about a person's background, you might not get enough time to talk about your own stuff.

But I think the doctors being teachers, advisors, it's really important to know who you're talking to and who you're getting advice from.

And it's also really important to understand that the fields are constantly changing, that our knowledge is constantly changing, and that the most important feature in a person who is helping you, in my opinion, is being curious and interested and trying to keep up with what's going on.

Yeah.

That was the other thing that me and the doctor on the AI show were talking about.

He's like, would you rather a human work on you or a machine?

And sometimes it's like, it's good to have a human work on you.

And I told him, yeah, if I was a machine, I'd want a machine work.

I'm not a human.

Stick with the humans.

Use the machine as a tool.

I think it depends.

It depends what you're talking about, but I think it's pretty hard for a machine to diagnose and understand.

The emotional aspect.

That's what he was speaking of.

Yeah.

Like the old bedside chat with what's going on, how you feel, and especially with depression.

I think you would need a person, like you say, and what's the background, and sometimes you just don't get along with people as well as others, so you got to go meet them.

So in the show notes will be on all the information on the therapies that we talked about, ECT and the magnetic stimulation.

One of my question was, who should you see a patient, or I think I need to be a patient, who should I go see and for what?

The place to start is usually your primary care doctor.

Okay.

So whoever you see when you have something go wrong physically, that would be your primary care doctor, the person who does your yearly check-in physical, right?

Primary care doctors have the hardest job in the whole world, in medicine by the way, because they have to know something about everything.

Oh, I see.

He's the one I would go, you know doc?

Yeah.

And he might tell me, you know, Dan, I don't want to give you Prozac or whatever, go see this person first and be a psychiatrist or-

So maybe we'll suggest one of the two referral.

Or, you know, and primary care doctors, I mean, it's very, their job is so hard.

But some primary care doctors will try an antidepressant or two or three before-

Yeah, just to save you the trouble and they know you better.

Some will, you know, say, you know what, I want you to see somebody who does this, this right away.

And then-

Okay.

So really your primary care doctor is a very good place to start.

And going from there, it depends on who you have access to and how complicated you are.

And especially since your primary already knows your other big health challenges and things like, you know, you about your body.

If they had any knowledge at all about the neural stuff, the mental stuff, they could be a good, a big funnel.

Yeah, I think a primary care doctor is the conductor of the orchestra.

So for people who have like many different health problems, you know, and they sort of add up as people get older, right?

But if you have the cardiologist over here and the dermatologist over there, and you have the gastroenterologist there, the primary care doctor is trying to keep track of, you know, what everyone is doing, how it all comes together, right?

Yeah, so that's a good place to start.

Perfect.

That's a simple, perfect answer.

Thank you.

All right.

Well, take care, Daniel.

Thanks, Dr.

Allen.

Okay.

Have a good night.