The Evolution of Brain Stimulation Therapy

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 though 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 how we treat people with severe depression, especially those who 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 Institute 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 brain stimulation tools. We’ll dispel misconceptions about brain stimulation, learn how seizure therapies can help with depression, and touch upon what the future holds 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 how 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 thought, what is this thing? You know, what…it seemed magical to me. And I remember asking my attending, who was Rich Weiner, how does ECT work? And he said, we don’t really know.

And I thought, this is my purpose as a scientist, I just wanted to learn everything I could about ECT, I wanted to understand how it works, and why it’s so rapidly effective. And so, that got me hooked. 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 grandfathers 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 thought, 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 thought was if you had epilepsy, then you wouldn’t develop schizophrenia. And likewise, the people with schizophrenia 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 schizophrenia can get epilepsy and vice versa. And also now we know that electroconvulsive therapy is actually more effective for depression than for schizophrenia. So, even though 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 how we treat people with severe depression, especially those who 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 hospital, 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 whole 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 brain 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 body to not move, so the body 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 body, and that could injure the body. Today, with the anesthesia, the body does not move, so the body is protected. And you’re being monitored throughout 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 brain has a seizure, but your body doesn’t really have a seizure.

Dr. Lisanby: That’s exactly right.

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

Dr. Lisanby: To be honest with you, no, we don’t have complete knowledge of how it works. But I can say we’ve learned a lot over the decades about what ECT does, and there are theories about how 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 brain that affect brain function. Specifically, ECT affects many of the same chemicals that our medications affect. It also induces neuroplasticity. So, changes in the functioning of brain cells that alter the way circuits in the brain 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 brain, plasticity meaning change. The concept of neuroplasticity is that our brains 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 brain that we see with ECT that are thought to be related to how ECT works is the growth of new cells in the brain. You know, when I was in medical school, we were taught you’re born with a certain number of brain cells and that’s it, and you just lose them over time. You don’t ever gain any. It turns out we were wrong. Turns out we actually do gain new cells in response to different things, and ECT is one of those things that can induce that. So, one of the theories about depression is that there’s a loss of plasticity, that the brain cells have lost their resilience, or their ability to respond. And some antidepressant treatments, like ECT, have been shown to reverse that process.

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

Dr. Lisanby: So, ECT can work in people in whom 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 how potent it is in achieving remission from depression. Another way that ECT is better is that it’s faster. So, when you start 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 who are at significant risk of suicide, those days can be the difference between literally life and death.

Dr. Gordon: Is there a way to know who 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 who 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, though, is that we’ve learned a lot over the years about how to reduce the risk of memory loss. And some of that has come from studies funded by the National Institute of Mental Health. We’ve learned how to modify the way the treatment is given, literally where to put the electrodes on the head. We’ve learned how to modify the amount of electricity that’s given. From this, we’ve modernized ECT practice in ways that have significantly reduced, though 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 how 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, how powerful is it? About brain imaging, like magnetic resonance imaging? It’s that strong. So, on the order of say a two Tesla, which is a measure of how strong the magnetic field is. And those strong magnetic fields enter the brain and induce tiny electrical currents. And so, these tiny electrical currents are strong enough to stimulate the brain cells.

Dr. Gordon: Wait, wait, wait, so you can hold this paddle over someone’s head, and those waves travel through the skull, and they stimulate the brain 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 electoral currents and vice versa. And the clever thing about how 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 brain. And one of the cool things about TMS compared to ECT is we can be very precise about parts of the brain we’re stimulating. ECT stimulates literally the whole brain, whereas, with TMS, we can go in and target specific circuits in the brain, 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 how potent it is, and how 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 how 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 potency of TMS and speeding up its benefits.

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

Dr. Lisanby: Because TMS is very precise about where you target in the brain, 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 brain scan at the beginning, and you use the brain scan with your own brain 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 home this notion that depression is a brain disorder, right? When you’re stimulating the brain 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 who’s given these life-saving therapies to patients, to see a patient change and respond after you’ve stimulated their brain.

Dr. Lisanby: So, it really is transformative to see how 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 brain stimulation, drives home the point that depression is not a moral failing, it’s not like a weakness. It is a brain disorder, and it can be treated by stimulating the brain. 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 holds 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 brain stimulation, and how 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 hope you’ll join us for the next podcast.

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