Faith Wang
Wang_1
Tyler was 28 years old | when he told his psychiatrist | he had no more hope. By that point | he’d attempted suicide seven times | in just over a decade. He’d tried every FDA approved treatment for depression.
All of them.
Hijjar 1:
Therapy and 20+ antidepressant medication,
Wang_2
It didn’t work.
Hijjar 2:
13 rounds of Electric Shock therapy
Wang_3
It didn’t work.
Hijjar 3:
6 rounds of transcranial magnetic stimulation
Wang_4
Imagine shooting magnetic beams through your head to stimulate the brain cells… In any case… It didn’t work.
Hijjar 4:
Six rounds of ketamine infusion
Wang_5
Didn’t work.
Hijjar 5:
So I got in my car one day and I was driving on the highway and I thought to myself, you know, I can just unbuckle my seatbelt and hit the sidewall and people will think it’s an accident.
And I was like, but I think I want to say goodbye to my mom. So I called my mom and I said to her, I love you so much. And I started choking up and crying a little and she could tell something was wrong. Tyler, I don’t know what’s wrong, but please don’t do anything that you can’t take back.
I said, I’ve fought long enough, and (she) said, please just call your dad,
Wang_6
So he did.
Hijjar 6:
And it’s really bizarre, but my dad said to me. You know I love you, and I can’t wait, I hope you don’t do it. But I can’t stop you. But one thing, I do not want you to wreck one of my cars. I, the comment shocked me, just kind of snapped me out of it for a second.
I just said, Okay, he goes, Why don’t you come home? I’m home and we can talk. So I went home. I gave my dad a hug and I bawled like a baby.
Wang_7
There’s a name for what Tyler has. Treatment resistant depression. It’s exactly what it sounds like: depression that doesn’t respond to any of the conventional treatments, not pills, not electric shock, not therapy.
And what Tyler was feeling, despair, the loss of agency, is common \ in those with treatment resistant depression.
Hijjar 7:
The biggest thing I felt, I would say, is the fear. When is my next episode going to happen? I just, there was no control. I was powerless.
Wang_8:
This is True Stories in Sound. I’m Faith Wang.
So, what can modern medicine offer patients like Tyler, whose depression seems to resist all treatment? What they want is something almost magical, a switch. Something you could just flip, and turn off the depression. Something that easy, that powerful.
Well, it seems that someone may have developed that switch.
[Archival sound] : A potential new approach, let me show you what l am talking about, device like this, it’s implanted like a pacemaker just underneath their collarbone , at least two wires inserted directly into the brain, And on the outside the doctor can literally flip a switch, turning it on.
Wang_9:
The switch is called DBS, short for Deep brain stimulation.
So how does it work? Well, imagine your brain as an electrical circuit in a computer. Neurons are connected to each other by axons, which are basically communication cables .
A lot of times, when the brain is damaged by something like Parkinsons, you can see it… On an MRI scan, it’s very clear. There are certain parts of the brain that are shrinking or lesioning.
Wherever that damage part is, it’s causing the whole circuit to crash. DBS uses electrical stimulation to rewire the brain around the damage \by bypassing the dysfunctional area. Like a shortcut.
The technique was approved by the FDA for the treatment of Parkinson’s in 2002.
Okay, all that makes sense. So how is using DBS treating depression any different? …Now I said this before, but it’s important: Parkinson, you can see them. Depression. You can not.
Which means, yes, there may be a switch, a switch to rewire the problematic part of your brain, but it’s difficult on depression, because how do you locate the part you need to rewire \ when you can not see it?
And that’s the problem Helen Mayberg has been trying to solve for the last 20 years.
Mayberg 1:
So, I’m a neurologist. I was interested in the neurology of depression and l did experience.
Wang_11:
Mayberg looks at depression through the lens of the brain. She believes that depression, especially treatment resistant depression, is caused by neurological issues. For 15 years straight, she didn’t treat anyone, she did one thing, experiment, mapping circuits in the brain, trying to locate the invisible, the depression.
Mayberg 2:
over many years, different kinds of tools, let us get an idea about what areas of the brain don’t seem to work together when they’re depressed and you can start to get a map of Certain areas of the brain that are part of depression and certain parts of the brain are not.
Wang_12:
And one spot in the brain began to stand out. Subcallosal area 25, a part of the cingulate cortex.
Mayberg 3:
when you look in the animal literature, there were speculations about what it did. Because if you stimulate there in a monkey, it makes crying sounds.
When we did and other people did experiments, mapping, It didn’t light up when people got happy, didn’t light up when people got fearful. when you challenged people with a sad memory, it seemed to be very active.
Wang_ 13:
So, what is this area 25? If you look at a brain map, area 25 is shaped sort of like a tiny sleeping seahorse, resting on the left edge of the most central and deepest region of the brain. One medical journal describes it as one of the least understood regions of the cingulate cortex.
It is least understood and overlooked because there are no pathological changes in that area, you know, like the kind of damage Parkinson would cause to certain parts of the brain. So it won’t catch your eye on an MRI scan.
Area 25 doesn’t serve any function by itself. Instead, it talks to other parts of the brain. It’s an intersection that combines sensory, cognitive and autonomic processing at the core of emotional experience. It generates impulse. It’s like a processor for the computer.
Mayberg 4 :
Think about it when you get sad. If you’re watching the news and it’s really terrible, you get kind of inside yourself and then they have a happy story next and you break the negative mood, right? Because this system is a toggle. You need a system that says when this is negative, I need to stop what I’m doing, maybe make an assessment and then I need to make an action plan and move.
Wang_14:
But people with treatment resistant depression can’t toggle and remove themself from the negative. Because, Mayberg argues, their area 25 is too active, the processor is overloaded. The more active area 25 gets, the more depressive one becomes. When we think about depression, we picture a brain that is too negative or has lower energy. But really think about when you are depressed, in pain, really think about it, it’s because you are feeling too much. According to this theory, the reason you have lower energy is because the overwhelming waves of emotions are exhausting you.
So now, Mayberg has a location. The next step would be to install the switch using the same bypass rewiring methodology for treating Parkinson, focused now on area 25.
The idea was to use electronic stimulation to lower the activities on area 25, to turn it down.
But in the medical world, to turn an idea to FDA surgery takes decades. It certainly takes longer – when it’s using an invasive brain surgery to treat mental health compared to other diseases. But we will get to that later.
In 2003, FDA approved the first ever medical trial to use DBS to treat Treatment Resistant Depression.
Mayberg 5 :
go back 20 years . It’s a thought experiment. I have all these scans. I talked to the surgeon. Can he do this? And it’s a hypothetical, right? And now you’re going to go to the OR and you’re going to go into somebody’s brain and you’re going to put this in and you’re going to see what happens. Cause you really, have no idea if your idea is right. And I got very worried the first time, and the surgeon was very helpful to me. He said, Look, We’re going to go to the OR. The patient’s going to be awake, we will carefully turn it on and we will see what happened. If we do something and nothing happens, that’s good. We didn’t ever expect anything to happen in the OR. you’re nervous because.
You don’t want an idea to hurt somebody, right?
Wang_15:
and the first patient was implanted.
Mayberg 6 :
So when the first person we started stimulating, first contact, nothing. Second contact, nothing. Third contact, suddenly just different.
How can any, it’s indescribable because you had no idea what might happen and then something is happening.
Wang_16:
That moment, that “oh my god, something magical is underway” moment, happened in 2003 for Mayberg. 16 years later, 2019, Tyler was counting on something similar to save him from his own depression.
Tyler, if you’ll recall, is the guy we heard from the beginning of our story, who’s depression had resisted all treatment. That day he imagined driving his car into the highway retaining wall, his dad called the doctors working on that trial at Emory University.
At that point, Mayberg was running her third trial, and a patient had just dropped out. So Tyler was in luck. He and his family flew to Atlanta to receive the surgery.
Hijjar 9:
They bolted a crown type device on my head. They explained to me what they were going to do, Dr. Helen Mayberg was there, such a lovely lady.
And I said, you know what, I trust you guys. At that point I was so apathetic, I didn’t care if I lived or died.
During the surgery, they tried different settings.
Wang_17:
Like when you go to see an eye doctor.
Hijjar 10:
It’s really hard when someone says, you feel anything here, you feel anything now, and you just don’t know how to answer and ask questions. How do you feel? How do you feel?
I’m like, I don’t want to answer the wrong way because this is in my brain. So, I just tried to answer to the best of my ability, and the most honest way possible. I go, just wait a minute, I just, I’m just trying to really feel how I’m feeling there.
Mayberg 7:
We know which one should give the big effect. The patient doesn’t know which one’s the best. And we try all eight.
Wang_19
Eight settings, that evoke eight different sensations.
Hijjar 11:
And they hit one setting that made me feel very afraid. I got extremely anxious I was also very surprised that simply running electrical current in the brain like that could change my mood that fast.
I felt like I was crawling in my skin. Um, I’m like, could y ou turn that one off? Can you turn that off? And they said, sure, sure, sure.
Wang_20
And within seconds, he calms down. But Mayberg wasn’t calm.
Mayberg 8:
Every time you go to the OR, you’re always nervous. Is it
gonna be the same this time? So you’re sitting waiting. I know which
contact it should be, but I’m …..just waiting.
Hijjar 12:
and they woke me up and they tried a different setting
Wang_21
And that, is the setting Mayberg has been waiting for.
Mayberg 9:
when if you’re watching a patient’s face and they’re, you know, you can’t see much.They’ve got just their eyes. They’re bolted in there in a frame. It’s a very weird environment. All you can see is their eyes and all they can see is your eyes. There’s a way people look when you stimulate after about 20 seconds where I know they’re going to say something. I can just see it. I can’t, I know it’s like their, their eyes lighten up.
Hijjar 13 :
and I remember feeling good for the first time. In a decade, in 10 years, I mean, really good. The tension in my shoulders, you know, I just felt relaxed. I felt like it wouldn’t be an effort for me to sit up and walk around the room.
Mayberg 10:
So when people have this relief, it’s not because you hit 25. It’s because you change the connections to these other places in the brain. It’s like it’s like the whole system comes back online.
Hijjar 14:
Like, I didn’t realize I could feel that good. Not, not like euphoric good, but like normal.
You know, I would compare it to, it was like a feeling of like, It’s like a feeling I used to get when I used to make people laugh, or l see videos of soldiers coming home to their families. something as cliche as helping an old person cross the street.
Like you’re smiling right now, as I’m describing this stuff, it’s just those good feelings. And I hadn’t felt those feelings In a long time,
Mayberg 11:
There’s something about their facial expression that and I’m waiting to see what they say,
Hijjar 15 :
I said: this is the setting that I want. depression feels like there’s a weight. It’s like dragging around a boulder and that heaviness can bury people. And for the first time in years, I felt lighter.
Mayberg 12:
And there is a joy, happy dance kind of in my head, like, yes, it’s there. And when I see it, I know what’s going to happen to the person going forward. It becomes the reinforcement that this is the first part of all of this.
Wang_22
After the surgery, the doctors would turn off the DBS device inside of Tyler’s brain for a month, just to eliminate any possible placebo effect, which means Tyler would soon be depressed again. And Tyler knew that would happen, and sure enough, within a month, it did. But this time is different, because this time he had something he hadn’t had for too long.
Hope.
Hijjar 16:
I was like, wow, okay, so this, I’m not feeling good. I have low energy. but I don’t want to take my life because I know this is going to pass. I know, right?
Wang_23
It’s worth noting that Mayburg’s research has its detractors, and the procedure could still be years away from FDA approval. But patients like Tyler are desperate. There are 2.8 million people with treatment resistant depression in the US. And only a tiny percentage of those, around 400 people… have received DBS treatment so far.
Mayberg 14 :
And as we read people’s stories, it almost feels to me like patients look and go, I should be able to assume the risk, and I should be able to get it, whether it’s approved or not,
And, and this is very hard. It’s like you’ve got your face pressed against the window and you’re starving and there’s food.
Wang_24
Dr. William Anderson of John Hopkins University, performs DBS for treating Parkinson’s, and is the author of the book Deep Brain Stimulation: Techniques and Practices. He’s skeptical of Mayberg’s results. Even if the FDA approves the therapy at some point based on Dr. Mayberg’s data – Anderson told me the technique would need at least a decade of follow up to know for sure that any benefits were durable. The trials that he’s seen just aren’t convincing…
Anderson1:
Approximately 10 years ago, there were two very large industry sponsored trials of deep brain stimulation for major depression. Unfortunately, both of those trials had to be stopped, uh, because, uh, the patients, uh, there was no consistent improvement in the patient’s symptoms.
Of course some patients do very well. We just heard one of those stories. But for Anderson, that’s not enough.
Anderson2:
And that’s really the critical thing, you know, Uh, because there are always statistical fluctuations with these clinical trials. And so you may see fantastic papers that show two or three patients that respond and you think, Oh, this is great. This is going to change the world. Uh, that’s very rare. It’s very rare to happen.
Wang_25
For the patients for whom DBS works though, the procedure can be so life changing that they aren’t willing to wait for FDA approval. Abbey Robbions struggled for decades, and tried every other way to treat her condition, just like Tyler. This is the letter she wrote to the DBS medical trial. This is what Abbey wanted the doctors to hear.
Abbey 1:
I work hard but I get nothing to show for it except for still being alive. I know no treatment is going to do all the work for me. All I want is for it to be possible for me. All I want is just enough help for my hard work to make a change.
Maybe people like me are more likely to get dementia because it’s not within human capabilities to maintain this state of being. Maybe losing my mind will be the only option my brain will have to stay alive.. If there is any possible way to get DBS sooner, please find it for me. I am absolutely begging you.
Wang_ 24
And the doctors listened. Abbey got in the trial. It took a little longer for her, the doctor had to turn the stimulation up several times within a year for her to start to feel better. But it worked.
Abbey 2:
The doctor, he was like, did you want to turn it down? So the battery lasts longer. I was like don’t fucking touch a thing.
Sorry, Sorry, I was like no don’t don’t. Keep it where it is, or I will slit your throat. I didn’t say that, but I don’t care that it’s, I’m not going back to how I was before for anything.
[music transition]
Wang_25:
And that, perhaps, is why people like Mayberg keep going.
Scientific breakthroughs are covered way more than failures, even though the two are often intertwined.
Mayberg:
We’re going to design it better. We’re going to try to get it right. The ultimate validation as a scientist to have people go, we’ve watched that you didn’t give up. You took the hit of everybody saying you’re wrong. It didn’t work. You fall down four times. You get up at five.
And if DBS is going to be the solution to treatment resistant depression, that’s the kind of determination it might take.
This episode was reported by me, Faith Wang, for Columbia University Journalism School. It was edited by Daniel Alarcón. Music from Sang quan and tunetank.
Thanks for listening.
Telling True Stories in Sound 