Daniel Knoepflmacher, MD (Host): Hello, and welcome to On the Mind, the official podcast of the Weill Cornell Medicine Department of Psychiatry. I'm your host, Dr. Daniel Knoepflmacher. In each episode, I speak with experts in various aspects of psychiatry, psychotherapy, neuroscientific research, and other important topics on the mind.

Our topic today is electroconvulsive therapy, or ECT. ECT is a form of neuromodulation, a treatment where nerve activity in the brain is altered by delivering direct stimulation, in this case, with electric current. It is one of the most effective and rapid-acting treatments available in the field of Psychiatry. Yet, despite its well-established positive results, ECT has been stigmatized by negative representations in popular culture, like the portrayal in the film One Flew Over the Cuckoo's Nest, which bears little resemblance to the reality of contemporary treatment.

I remember my first experience working with a patient undergoing ECT. She was a 75-year-old woman with textbook features of major depression, visibly burdened by hopelessness, suicidal thoughts, and impaired thinking. She was sapped of all energy and she was moving slowly. course of ECT, I watched as she emerged from that shell. I got to know her, finally, as someone who smiled easily, looked forward to the future, and felt a sense of amazement that she was able to feel like herself again. It was an almost magical transformation that I will never forget.

Today, we'll delve into this transformational treatment and discuss other forms of neuromodulation that can provide definitive recovery from some of the most severe forms of psychiatric illness. I'm pleased to have an expert on this topic joining me today, Dr. Dennis Popeo. Dr. Popeo is the Director of Neuromodulation for the Weill Cornell Medicine Department of Psychiatry. Dennis, it's great to have you with me on the podcast. Thank you for coming on.

Dennis Popeo, MD: it's a pleasure to be here.

Host: Well, my first question to all guests that come on this podcast is about their background. So, will you share with us how you got here and the path that you took to become a psychiatrist who now runs the neuromodulation service here at Weill Cornell?

Dennis Popeo, MD: i started off in medical school thinking that I was going to be a surgeon. And then, I realized I did not like surgery at all. And so, I realized one of the few things that I really enjoyed was Psychiatry. So, I ended up in Psychiatry. And I knew that I wanted to stay in the realm of academic medicine. And I knew that I wanted to do a fellowship after my General Psychiatry, Adult Psychiatry training.

And since I grew up with a large extended family of older folks, actually. One set of grandparents had 10 brothers and sisters between them, the other set had six brothers and sisters and we all lived in the same area, so I had a lot of older folks around as I grew up. Anyway, so that led me to do a fellowship in Geriatric Psychiatry. And a lot of older folks ended up getting ECT where I trained. And so, I thought it might be a good idea for me to learn about ECT so that I can do the best to care for the older adults that I like to care for. And once I started with the ECT, I realized I had a very sort of similar situation that you did where I would actually see people get significantly better, significantly faster and really make a difference in their lives.

Host: Just because of the immediate, positive effects, but also it's procedural, in some ways, it's one of the more surgical aspects of Psychiatry.

Dennis Popeo, MD: Yeah, definitely. And I think that we're definitely applying something, you know, in a very direct measure to the brain, which really sort of also made me more interested in the procedure and then in neuromodulation in general.

Host: Well, let's start with ECT. And if you could, tell our audience what ECT is and also how was it developed.

Dennis Popeo, MD: Sure. ECT or electroconvulsive therapy was actually developed almost on accident. So, a long, long time ago in a galaxy far, far away in a place called Austria, a Hungarian psychiatrist named Ladislav Mucina was working on an epilepsy ward. And he noticed that when patients came in to the hospital who had schizophrenia and also had a seizure disorder, that after their seizures, the signs and symptoms of their schizophrenia seemed to improve. And so, he thought maybe we can use a convulsion to treat schizophrenia. So, he went to the literature and found that you can actually induce convulsions or induce seizures by giving people intravenous infusions of camphor oil. And so, he found a patient that had schizophrenia but did not have a seizure disorder. He infused camphor oil into his bloodstream. The patient had a seizure and the signs and symptoms of his schizophrenia got better. And so, he started doing this more and more with patients there in Austria and patients got better and better.

After about a year or so, a couple of Italian scientists named Cerletti and Bini were working on applications of electricity in Medicine, and they realized that you could also stimulate a seizure by applying electricity to the brain. And so, the idea of electroconvulsive therapy was born. It came to the U.S. in 1940, first stopped over at one of our colleague institutions here in the city. But then, it was presented at the American Psychiatric Association after that happened, electroconvulsive therapy blew up. Back in the day, it was actually called electroshock therapy to differentiate it from insulin shock therapy, where again, back in the '40s and '50s, we didn't really have a lot of medication. So, we would put people in hypoglycemic comas to treat their schizophrenia, which worked when the patients survived.

Host: And so, this was a big advancement based on those survival rates.

Dennis Popeo, MD: Yeah, it was a huge advancement. And I think ,when we think about psychiatry today, if you will, you know, we have a whole lot of things in our armamentarium, right? We have different types of therapies. We have different types of medications and different classes of medications. And even within classes of medications, for instance, there are like five or six SSRIs that are available to us to use. But back in the '40s, there were no medications, right? The therapies that we think of today as part of everyone's argumentariums, cognitive behavioral therapy or dialectical behavioral therapy, they hadn't been developed yet. So, we had Freudian psychoanalysis and others of that school and long-term institutionalization for our sickest patients. So when ECT came around, it was something that actually worked really well for our very sick patients to the point where at one point in the late '40s, 'early 50s, nearly 99% of patients with schizophrenia in the United States were receiving ECT to treat their disease.

Host: Amazing.

Dennis Popeo, MD: Yeah. As psychiatry grew, and as our understanding of the brain grew, and as our understanding of pharmacology grew, medications were developed. And so, in the mid-50s, thorazine was developed. And it turned out that that actually worked really well to control the signs and symptoms of schizophrenia. So, that is one of the first paradigm shifts that we have in Psychiatry, where we moved from, you know, therapy and ECT and other what we call somatic therapies like the insulin coma therapy into pills. And as thorazine was developed, other antipsychotic medications were developed that followed with some of our antidepressants being developed, which culminated sort of in the '80s with another huge paradigm shift, which was the development of the SSRIs. And once SSRIs were developed, ECT really sort of fell by the wayside as a treatment for depression and a treatment for other forms of mental illness. But it was always still there, because some people didn't respond well to medications.

Host: And now, it seems, I mean, ECT, as you said, is still there because for those who don't respond, it's very effective. And we're starting to think about some other procedures again beyond medications, which we'll talk a little bit about more, I hope, later. But before we do that, I want to ask you about what happens inside the brain. We know that there's a convulsion.

Dennis Popeo, MD: Yeah.

Host: But describe what's happening in the brain as far as much as we know that makes this treatment so effective.

Dennis Popeo, MD: Yeah. So unfortunately, like most of the things in Psychiatry, and a lot of things in Medicine, we don't really know exactly what's going on. So, we know some things. We know that ECT loosens up the blood-brain barrier and also dumps a ton of neuropeptides, neurotransmitters, and catecholamines into the brain. And so back when we thought that depression or mental illness was caused by chemical imbalances, if you will, we thought maybe that's how ECT worked. We also knew that ECT sort of rebooted the deep neuroendocrine structures of the brain. Those structures that helped create cortisol and stress reactions. And we knew that, you know, decreasing cortisol and interacting with those areas also seemed to reduce depression and things like that.

These days, we don't really think too much about that, what we call the monoamine hypothesis of depression, the idea that there is chemical imbalance. We think more about circuitry and the different circuits running from our prefrontal cortexes to our limbic system and to our amygdala and things like that. And we know that ECT affects those as well. And I think someone in this podcast has probably used the word neuroplasticity before. And so, we know that ECT stimulates neuroplasticity in various ways. We know it increases something called brain-derived neurotrophic growth factor in the brain, and that also promotes neuroplasticity.

And so, the way that I usually explain it to people is that there's a bunch of things going on. It has to do with both the chemicals that your brain releases during the ECT, the changes in the brain that those chemicals have on the substrate, as well as the receptors in your brain. And although, we don't know exactly what's going on, we do know that it works. I usually tell my patients that, you know, when you think about rebooting your computer, this is kind of like rebooting your brain.

Host: Tell us about, as you understand it from listening to your patients, how they describe the experience of both getting ECT and then what they experience as a result of ECT.

Dennis Popeo, MD: My patients tend to tell me a couple of things about ECT. The first thing they mention is that the anesthesia gives them a very nice sleep. So, it's the same medication that you use for colonoscopies and things like that. You fall right asleep, and it's a quite nice sleep. Aside from that, as the procedure goes on, patients start to notice little changes. And it's interesting, because I think the folks around the patients notice the changes before even they do. So, you know, they notice that their relative is smiling a little bit more, or making a little bit of a joke here and there. When I take a look at my inpatients who, I treat, and these are sort of the sickest of the sick patients, like if they're very depressed, they probably haven't washed their hair for a while, they probably haven't showered for a while, they haven't really been eating. But after the second or third treatment, you notice that they're eating a lot better. They may put on a little bit of the weight that they lost from the depression. And I always find it's a big deal when they wash their hair. So when they come to the ECT suite with like freshly washed hair, that always makes me think, "Okay. They're getting better. They're starting to turn the corner."

Host: Earlier you brought up how ECT remained gold standard treatment for people who had failed various medications to treat depression, what we call in the field treatment-resistant depression. So, I would like to ask you when should someone with depression be considered for ECT, in your opinion?

Dennis Popeo, MD: So in my opinion, as soon as possible. So, I think that we've done a big disservice to our patients. And I think the disservice is because there's still a lot of stigma surrounding ECT. You mentioned One Flew Over the Cuckoo's Nest, that did a disservice to ECT and Psychiatry in general. In the 1970s, like sort of right after that came out, there was a huge, what we call the deinstitutionalization phase of Psychiatry, where we took people out of institutions, and we were allegedly going to care for them in the communities and in outpatient settings. Of course, that never happened for various reasons.

So, I think there's a lot of stigma, and I think what ends up happening between that and the fact that there are so many medications to choose from, that we tend to prescribe someone medication after medication after medication, and then maybe a combination of two different medications, and then we may add an antipsychotic medication or a mood-stabilizing medication to see if that will affect their depression. And I think that that does our patients a huge disservice.

In the research world, we think about treatment-resistant depression as patients who have had their symptoms not respond to two different medications of two different classes. So, for instance, if you start someone on an SSRI and they get better, that's great. But if they don't get better, you shouldn't give them a different SSRI, a different medication in the same class, right? There's really no difference between, say, Prozac and Paxil, if you will. So, you want to change to something else. And then, at that point, if you give them, say, an SNRI, which works differently than the other one, and they do well on that, that's great, you've solved their depression. If they don't do well on that, then it's time to start thinking about, you know, other things. And at that point, I start to think about neuromodulation on one hand or, on the other hand, say, a second medication that's added as an adjunct, right? Whatever the medication that they're taking.

Unfortunately, there's not a lot of data about what you should add to a particular medication. We know in some cases, like for instance, in patients who are depressed and elderly, we know adding an anti-psychotic medication called aripiprazole seems to be very effective in treating treatment-resistant depression. But if it's not, then you really should consider this neuromodulation, whether that's transcranial magnetic stimulation, whether that's a ketamine infusion, or it's ECT.

So, since I work here at a big academic institution, I see a lot of patients who have been suffering with depression for years and years and years. And the doctors in the community have tried every medication and every combination of medications. And, you know, even maybe some of the neuromodulation stuff. By the time they get to me, it's been like five years of being severely depressed. I think that that's a shame. That person should have come to me four years ago to think about the ECT. So, that's my plug for treating depression way more aggressively.

Host: That's depression. But what about other indications for ECT? You mentioned schizophrenia in the history of ECT, but can you speak about some of the other conditions?

Dennis Popeo, MD: Yeah,. So, we know patients with schizophrenia do respond to electroconvulsive therapy. In general, the way that I look at treating a patient with schizophrenia is that, you know, we should try to exhaust some medications first. But again, there are lots of different antipsychotic medications. And really, there are only two or three that stand out as different, right? So if you start on one antipsychotic medication and that doesn't work, then, you know, you should consider moving on to a medication called clozapine, which is a really good medication. It just requires a lot of work on the patient's part in that they have to get blood tests every week for a while.

But if the clozapine doesn't work, instead of adding another antipsychotic medication to that medication, if you add ECT, research shows us that ECT plus clozapine works better in relieving these patient symptoms than either one alone does. So, they really sort of work synergistically. And in fact, the ECT tends to have effects much longer for patients than they have had the ECT. So, the good effect extends a lot longer not just during the actual acute treatment phase. And again, that may be due to the neuroplasticity that ECT promotes.

Host: And what are the most common adverse effects? I mean, commonly known that there can be effects on memory. I'm just curious, again, as someone who's seen a lot of ECT, what has been your experience of the adverse effects?

Dennis Popeo, MD: Yeah. So, the memory and the cognitive problems are the things that people complain about the most, and I think that our people are afraid of the most. And there are some other side effects that we think about when we do ECT. We want to make sure that the patient has a good cardiovascular system. You know, we want to make sure that their heart is strong because ECT can make your heart beat really quickly. It may increase your blood pressure. In general, we can take care of those things with medications. But we want to optimize a patient for ECT just like we would optimize any patient before general anesthesia or before surgery.

But the cognitive issue is the issue I hear about all the time. I hear people saying, "Oh, I don't want to be turned into a vegetable. I don't want to forget everything." And in general, ECT does cause confusion for people, especially during the time that they're getting ECT. You know, if you think about it, we're giving you general anesthesia. We are treating you with electricity, which can mess up the electrical milieu of your brain for a short period of time. And we're giving you a seizure, which we know can cause what we call a postictal phase, or the area at the time after the seizure, then that patients can be a little slow, a little groggy, and a little confused. And then, we tend to treat people two or three days a week, so then they have two or three days of this groggy confusion.

So, I always tell my patients, during the course of ECT, you're going to feel confused. You're going to feel foggy. If your spouse tells you to do something, you're probably not going to remember it. You're not going to remember what you had for breakfast that morning or things like that. And that's completely normal and that, for the most part, goes away. It's very rare for people to have cognitive problems after a course of ECT, especially when you think about, you know, moving around between like six months, eight months, 12 months after ECT. Most people's cognition returns to normal. Some people do complain of memory problems after ECT. The interesting part is when we look at the data, it's really hard to pin down and match what they're subjectively complaining about to objective findings on neuropsychological testing or memory testing or things like that. So, I always say you will be a little bit confused during the course of the treatment, that generally goes away. In fact, for the most part, for most people, it goes away.

Host: So, it's really forgetting the time around the treatment is the biggest memory change.

Dennis Popeo, MD: Yes. I mean, basically, you know, what I tell people is that, your short-term memory just is not going to get encoded into long-term memory. You know, it's a little bit more complex than that, sort of on the neuromolecular level. But in general, that's sort of what happens.

Host: Experientially.

Dennis Popeo, MD: Yeah.

Host: we only have a few more minutes, but I want to jump into a big topic, which we just talked about ECT as one important form of neuromodulation, but can you tell us about, you've alluded to them, but some of the other forms of neuromodulation that are currently being used?

Dennis Popeo, MD: Yeah. So, we consider things like ketamine infusions as a neuromodulation, even though it is a medication like other things, probably because you have to come in to the hospital to receive them effectively. So, that's one thing. Transcranial magnetic stimulation is another form of neuromodulation that uses a magnetic field to affect areas of the brain. That's been shown to be helpful for depression, and there's a lot of research into looking at transcranial magnetic stimulation for things like OCD, obsessive compulsive disorder, and for PTSD. There is something called deep brain stimulation, which is used extensively in Neurology for the treatment of Parkinson's disease. But if you move the leads to areas of the brain that are associated with OCD and with depression, deep brain stimulation does a good job of treating very treatment-refractory OCD and some treatment refractory depressions. The Deep brain stimulation for depression is still quite experimental, but less so the OCD.

And then, there are new things coming out every day. So, this idea of near-infrared light has been shown to sort of affect mitochondria, which are the little powerhouses of the cells, if you remember from your initial biochemistry course. And so, there's a lot of research going on about using this near-infrared light to see if we can stimulate areas of the brain to affect depression and Alzheimer's disease, things like that.

There's some people actually here at Weill Cornell using focused high-frequency ultrasound to affect areas of the brain. They're actually looking at the ultrasound as a less invasive way to treat Parkinson's. Because even though deep brain stimulation works really well for Parkinson's, we are putting needles into your head and leaving them there. And of course, I'm sure someone has, or if they will be talking to you about psychedelics, things like MDMA or things like psilocybin. We do consider those sort of neuromodulation as well, or at least expand sort of our definition of neuromodulation to include those things. And there are some very promising studies, but a ton of work has to be done.

Host: Yeah. And I guess all of these, whether it's chemical or through energy and the different forms you are describing are really creating rapid-acting effects that are changing nerve activity in the brain. So, it fits that definition of neurostimulation.

Dennis Popeo, MD: You know, one of the good things about these neuromodulation treatments is that they occur so rapidly, and patients can recover rapidly. So for instance, not every patient is going to respond to TMS. However, a full TMS course can be anywhere from one week to three weeks. You don't even start feeling the effect of an antidepressant medication until the fourth week. And sometimes not the full effect until six to seven weeks. So, you know, it cuts down the amount of time. So, you can do TMS. If it doesn't work for you, then you find out it doesn't work in a very short period of time so that you can move on to the next thing so that you can treat your depression rapidly, which is what we need to do.

Host: We do need to do. I mean, we've talked about on other episodes about Precision Psychiatry and faster forms of TMS. And I hope maybe as you leading this neuromodulation service and things grow, we'll come back and we can talk about those some more. Let me just ask one last question, which is if you can recommend resources for patients, clinicians who want to learn more about neuromodulation or ECT specifically.

Dennis Popeo, MD: Yeah. I always start with recommending NAMI, the National Association for Mental Illness. I think it's nami.org is their website. I think that is an excellent resource for anyone who is dealing with a mental illness or has a loved one dealing with a mental illness.

Aside from that, if you are interested in ECT, I would say go to your good friend Google, because although there are not a lot of ECT practitioners across the country, there are a lot of places that do ECT in large cities. Obviously, New York, Boston, you know, up and down the east and west coast, but also in the middle of the country. And there are plenty of things and plenty of places that do ECT that you can find out about.

And it's sort of the same thing with ketamine and with TMS. Both NAMI and Dr. Google can help you find those resources. And I always recommend, if you have a very large academic medical center nearby, check out their website. Also, a lot of those large academic medical centers have really excellent patient information sites as well

Host: Well, Dennis, this was great, to have you here, getting this opportunity to discuss ECT and neuromodulation with you. I'm impressed with the work you've done here already to grow our neuromodulation service at Weill Cornell. I know there's more to come.

thank you for joining me on the podcast today and helping us understand the great potential of neuromodulation.

Dennis Popeo, MD: You're welcome. It was a pleasure to be here and I'll be very happy to come back whenever you'd like.

Host: I'll take you up on that. And thank you to all who listened to this episode of On The Mind, the official podcast of Weill Cornell Medicine, Department of Psychiatry. Our podcast is available on all major audio streaming platforms, including Spotify, Apple Podcasts, and iHeartRadio. If you like what you heard today, tell your friends. Give us a rating and subscribe so you can stay up to date with all of our latest episodes. We'll be back soon with another episode.

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