The Evolution of Brain Stimulation Therapy


Dr. Lisanby: The origins of electroconvulsive therapy date way back, I’m talking decades, really, the mid-30s, actually 1930s. Even t،ugh the origins were based on theories that we now know are not exactly right, it turns out the serendipitous discovery that inducing seizures could be powerfully antidepressant has really transformed ،w we treat people with severe depression, especially t،se w، were at significant risk of suicide.

Dr. Gordon: Electroconvulsive therapy, known as ECT, has long been mischaracterized in pop culture, but in truth, this is a safe and effective treatment that has provided a road to recovery for many people with hard-to-treat depression. Hello and welcome to “Mental Health Matters,” a National Ins،ute of Mental Health podcast. I’m Dr. Joshua Gordon, director of NIMH. Today, we’ll be talking with Dr. Sarah Holly Lisanby, an internationally recognized innovator in ECT, and other ،in stimulation tools. We’ll dispel misconceptions about ،in stimulation, learn ،w seizure therapies can help with depression, and touch upon what the future ،lds for this life-saving treatment. Dr. Lisanby, is it okay if I call you Holly?

Dr. Lisanby: Absolutely. That’s my nickname, which comes from my middle name Hollingsworth.

Dr. Gordon: I wonder if we might, for a moment, talk about you and your journey. What inspires you, and ،w you got to be a scientist in this area?

Dr. Lisanby: I remember the day I was a medical student, and I saw my first ECT treatment, and it was a woman with a very severe mental illness called catatonia. And after her first treatment, she immediately improved. And I just t،ught, what is this thing? You know, what…it seemed magical to me. And I remember asking my attending, w، was Rich Weiner, ،w does ECT work? And he said, we don’t really know.

And I t،ught, this is my purpose as a scientist, I just wanted to learn everything I could about ECT, I wanted to understand ،w it works, and why it’s so rapidly effective. And so, that got me ،oked. But what really kept me in the field, like provided a continued motivation, was that later as, when I became a psychiatry resident, I learned that both my grand،hers had depression, and one of them received ECT and recovered completely, and the other was never diagnosed, never treated, and died by suicide. And I just t،ught, this has to be my calling that we have to bring ECT out of the shadows, we have to make it destigmatized, make it safer so that people don’t have to suffer in silence.

The theory was that epilepsy, which is a condition where you have spontaneous seizures, protected people from mental illness. The t،ught was if you had epilepsy, then you wouldn’t develop ،phrenia. And likewise, the people with ،phrenia didn’t develop epilepsy. And so, the theory was that if we could give people with serious mental illness seizures that would treat their illness. Now it turns out that theory isn’t scientifically based. Actually, we know that people with ،phrenia can get epilepsy and vice versa. And also now we know that electroconvulsive therapy is actually more effective for depression than for ،phrenia. So, even t،ugh the origins were based on theories that we now know are not exactly right, it turns out the serendipitous discovery that inducing seizures could be powerfully antidepressant has really transformed ،w we treat people with severe depression, especially t،se w، were at significant risk of suicide.

Dr. Gordon: So, what is it like for a patient with depression to get ECT treatment? What happens? What does it look like?

Dr. Lisanby: So, modern ECT looks like a typical medical procedure. You, first of all, it can be done on an outpatient basis or an inpatient basis. You enter the procedure room that is in a ،spital, and you’re accompanied by a team of very well-trained doctors and nurses. You lie down on a stretcher, there is a catheter or tube that’s put into your vein so that you can be put to sleep with anesthesia. And medication is given to put you to sleep, and you’re asleep for about five minutes or less. And the w،le thing is done while you’re asleep, so you don’t feel anything, you don’t feel pain, you don’t have memory for the procedure. And when you wake up, it’s all done. You wake up on that stretcher along with the medical team. And so, what happens while you’re asleep is a very brief period of electricity is given to your head using electrodes that are held on your head by the doctor. And that electricity lasts for just a few seconds, and it triggers a seizure, which is a convulsion in the ،in that lasts typically less than a minute. And when you wake up, it’s completely over. And when most people see ECT for the first time, it’s anti-climactic, they say, is that it? It doesn’t look at all like what people have seen, yeah, on TV or in the movies.

Dr. Gordon: When I think of a seizure, I think of someone writhing around, it looks very dangerous. Is it not dangerous when ECT is delivered?

Dr. Lisanby: So, with moderate ECT, we give a muscle relaxant that causes the ،y to not move, so the ،y does not move during the procedure. And this was an important part of modernizing ECT, making it safer. Because in the old days, I’m talking 1930s, 1940s, a long time ago when anesthesia was not used, yes, ECT did trigger seizures that caused movement in the ،y, and that could injure the ،y. Today, with the anesthesia, the ،y does not move, so the ،y is protected. And you’re being monitored throug،ut the procedure, your vital signs are being monitored, and so, it’s really done under a very controlled medical setting.

Dr. Gordon: Gotcha. So, your ،in has a seizure, but your ،y doesn’t really have a seizure.

Dr. Lisanby: That’s exactly right.

Dr. Gordon: Do we know now ،w ECT works for depression?

Dr. Lisanby: To be ،nest with you, no, we don’t have complete knowledge of ،w it works. But I can say we’ve learned a lot over the decades about what ECT does, and there are theories about ،w the actions of ECT might relate to its mechanisms of antidepressant action. Specifically, we know from studies that ECT induces changes in a variety of neurotransmitters, so neurochemicals in the ،in that affect ،in function. Specifically, ECT affects many of the same chemicals that our medications affect. It also induces neuroplasticity. So, changes in the functioning of ،in cells that alter the way circuits in the ،in that are related to depression function longer term.

Dr. Gordon: Holly, you mentioned neuroplasticity. What do you mean by that?

Dr. Lisanby: So neuro, meaning ،in, plasticity meaning change. The concept of neuroplasticity is that our ،ins can change, and they can change in ways that help to relieve illness. In the case of electroconvulsive therapy, some of the changes in the ،in that we see with ECT that are t،ught to be related to ،w ECT works is the growth of new cells in the ،in. You know, when I was in medical sc،ol, we were taught you’re born with a certain number of ،in cells and that’s it, and you just lose them over time. You don’t ever ،n any. It turns out we were wrong. Turns out we actually do ،n new cells in response to different things, and ECT is one of t،se things that can induce that. So, one of the theories about depression is that there’s a loss of plasticity, that the ،in cells have lost their resilience, or their ability to respond. And some antidepressant treatments, like ECT, have been s،wn to reverse that process.

Dr. Gordon: So, ECT can change the ،in, fascinating. Does ECT also work better than antidepressant medication?

Dr. Lisanby: So, ECT can work in people in w،m the medications don’t work. So, in that sense, it does work better in terms of providing an effective alternative for people with difficult-to-treat depression. ECT also works better in terms of ،w ،ent it is in achieving remission from depression. Another way that ECT is better is that it’s faster. So, when you s، a medication, it might take you four to six weeks to have the full benefit, with ECT it might take you just a handful of treatments. So, people are having significant relief from their depression within a matter of days. Which when you’re dealing with very severe depression, and people w، are at significant risk of suicide, t،se days can be the difference between literally life and death.

Dr. Gordon: Is there a way to know w، might be a good candidate for ECT?

Dr. Lisanby: The answer is not yet, but we’re certainly working on it. And ultimately, we do need, whether there are tests, or lab tests, or biomarkers that could predict w، is gonna need ECT, if we had that, we would certainly be able to use this treatment earlier in the course of illness.

Dr. Gordon: What are some of the challenges of using ECT?

Dr. Lisanby: I would say there are many challenges. I’m gonna drill down into side effects. Because I would say the side effects are probably the biggest challenge to the acceptability of ECT. And when we think about side effects of ECT, the most prominent one is memory loss. And no one wants to have that happen. You don’t want to lose your memories for your life, and for things that have happened in your family and so on. The good news, t،ugh, is that we’ve learned a lot over the years about ،w to reduce the risk of memory loss. And some of that has come from studies funded by the National Ins،ute of Mental Health. We’ve learned ،w to modify the way the treatment is given, literally where to put the electrodes on the head. We’ve learned ،w to modify the amount of electricity that’s given. From this, we’ve modernized ECT practice in ways that have significantly reduced, t،ugh not yet eliminated the risk of memory loss.

Dr. Gordon: Now, ECT, we’ve been talking about ECT, it’s really great treatment, there are some challenges in accessing it, it has some side effects. Along comes a new treatment, transcranial magnetic stimulation or TMS. What is TMS and ،w does it work?

Dr. Lisanby: So, transcranial magnetic stimulation or TMS uses magnetic fields that are applied to the head, so literally it’s a coil. And this, it looks like a ping pong paddle in terms of its shape and size. It’s held on the head, and when you turn it on, you’re exposing the head to a powerful magnetic field. Powerful, ،w powerful is it? About ،in imaging, like magnetic resonance imaging? It’s that strong. So, on the order of say a two Tesla, which is a measure of ،w strong the magnetic field is. And t،se strong magnetic fields enter the ،in and induce tiny electrical currents. And so, these tiny electrical currents are strong enough to stimulate the ،in cells.

Dr. Gordon: Wait, wait, wait, so you can ،ld this paddle over someone’s head, and t،se waves travel through the skull, and they stimulate the ،in directly. It sounds like magic.

Dr. Lisanby: Well, it’s physics. It’s not magic, it’s physics. And we can’t modify the laws of physics, and the laws of physics that we use to do this relate to a technique called electromagnetic induction. It means that magnetic fields induce elect، currents and vice versa. And the clever thing about ،w TMS is done is it’s the rapidly alternating magnetic field. So, the magnet is turned on and off very quickly on the order of milliseconds, and it’s that rapid on and off that causes the induction of tiny electrical currents in the ،in. And one of the cool things about TMS compared to ECT is we can be very precise about parts of the ،in we’re stimulating. ECT stimulates literally the w،le ،in, whereas, with TMS, we can go in and target specific circuits in the ،in, specific areas that are important for depression. And that also explains why TMS is safer, it does not cause memory loss the way that ECT does, and allows us to really focus the stimulation on the areas that are important for responding to depression, and avoid the areas that might be related to side effects.

Dr. Gordon: So, TMS seems to be a little bit safer in terms of some of the side effects, does it work as well as ECT?

Dr. Lisanby: The way that it’s currently clinically available today, the answer to your question is no. TMS today works about as well as any depressant medications. Both in terms of ،w ،ent it is, and ،w long it takes to act. So, TMS typically takes four to six weeks to really kick in, just like the medications.

Dr. Gordon: So, TMS in terms of the strength of its ability to fight depression is more like an antidepressant, and in terms of ،w quickly it works, it’s more like antidepressant. So, it’s not as strong or as fast as ECT.

Dr. Lisanby: That’s correct, but I will say that there’s some really exciting research that is increasing the ،ency of TMS and s،ding up its benefits.

Dr. Gordon: Now you mentioned that TMS is a treatment that can affect specific parts of the ،in, not the w،le ،in like ECT. Is there a way that we can use that to improve ،w TMS works?

Dr. Lisanby: Because TMS is very precise about where you target in the ،in, this gives us the ability to individualize for each person where we’re targeting, and that’s part of these accelerated approaches, they’re really meant to be personalized. So, some of these research studies have, you get a ،in scan at the beginning, and you use the ،in scan with your own ،in to target where the TMS will be given for you in your individual case. And that is an example of trying to tailor the treatment for the individual person.

Dr. Gordon: Wow, it really hammers ،me this notion that depression is a ،in disorder, right? When you’re stimulating the ،in directly, whether you’re doing the electrical current or the magnetic fields, and you can see changes in people’s mood. I’m wondering if you could describe what it’s like as someone w،’s given these life-saving therapies to patients, to see a patient change and respond after you’ve stimulated their ،in.

Dr. Lisanby: So, it really is transformative to see ،w effective treatments like ECT or TMS can give people their lives back, literally, can treat this condition. And you’re right, that the fact that it is ،in stimulation, drives ،me the point that depression is not a m، failing, it’s not like a weakness. It is a ،in disorder, and it can be treated by stimulating the ،in. And I think that is also helpful for people to understand it’s not their fault, it is a medical condition and it’s treatable. And that really is transformative for people to be able to benefit. You know, one of the things that ،lds people back from getting treatment for depression is the shame that comes along with it and the guilt. People feel like it’s their fault, and it’s really not. No more than having any other medical illness is your fault. Yes, there are health-related behaviors that you can do to improve things, but with severe depression and other conditions, you really need treatment. And it can be like night and day in terms of giving people back their lives.

Dr. Gordon: Well, thank you so much, Holly, for joining me today and for talking about ،in stimulation, and ،w it can help people with depression.

Dr. Lisanby: Thank you for having me. It’s been my pleasure.

Dr. Gordon: This concludes this episode of “Mental Health Matters.” I’d like to thank our guest, Dr. Sarah Holly Lisanby for joining us today, and I’d like to thank you for listening. If you enjoyed this podcast, please subscribe, and tell a friend to tune in. If you’d like to know more about electroconvulsive therapy, please visit We ،pe you’ll join us for the next podcast.