Facebook Live: Brain Stimulation Therapies
Transcript
SARAH “HOLLY” LISANBY: Hello, everyone. Thank you for joining me today for this discussion on brain stimulation therapies in recognition of National Mental Health Awareness Month. My name is Dr. Holly Lisanby. I'm a medical doctor and a psychiatrist. Here at the National Institute of Mental Health, I wear a couple of different hats. I'm the director of the noninvasive neuromodulation unit in the Experimental Therapeutics & Pathophysiology Branch in NIMH's Intramural Research Program. I'm also the director of the Division of Translational Research at NIMH, and I'm a part of the NIH BRAIN Initiative. The mission of the Noninvasive Neuromodulation Unit is to discover the mechanisms of action of noninvasive neuromodulatory treatments and to use this understanding to develop safer, more effective, and personalized interventions for serious psychiatric conditions, such as treatment-resistant depression and autism spectrum disorders. The treatments I work with include transcranial magnetic stimulation, or TMS, for short, and electroconvulsive therapy, or ECT, for short. ECT is highly effective for a broad range of serious psychiatric conditions, including treatment-resistant depression, mania, psychosis, and catatonia, but it can also cause memory loss.
SARAH “HOLLY” LISANBY: In contrast, TMS has an excellent safety profile and is FDA-cleared for treatment-resistant depression, obsessive-compulsive disorder or OCD, migraine, anxiety with depression, and smoking dependence. But TMS does not yet match the effect size and the therapeutic spectrum of ECT, and TMS is not yet approved for youth under the age of 15 years old. My lab has two research aims. The first aim is to make ECT safer by unpacking its active ingredients, that being the electric field and the seizure. And our second aim is to make TMS more effective by optimizing its dosage, personalizing its targeting, and discovering biomarkers to help guide patient selection. Brain stimulation therapies can help people with certain mental disorders, like major depression, who have not responded to other treatments. During the next half hour, I'll describe common types of brain stimulation therapies, and while they are used, I'll dispel some misconceptions, and I'll highlight NIMH-supported research in this area. I'll also take the last 10 minutes to take some of your questions. So please enter them as comments under the livestream post below, and I'll do my best to answer as many as I can before the end of this event.
SARAH “HOLLY” LISANBY: It's important to note that during the event today, I can't provide specific medical advice or referrals. Please consult with a qualified healthcare provider for diagnosis, treatment, and to answer your personal questions. If you need help finding a provider, please visit the website nimh.nih.gov/find-help. If you or someone you know is in crisis, please call or text the 988 Suicide & Crisis Lifeline at 988. You can also visit the website 988lifeline.org for more help and information. The Lifeline provides 24/7 free and confidential support for people in distress, prevention and crisis resources for you or your loved ones, and best practices for professionals in the United States. Brain stimulation therapies hold promise for people with certain mental disorders who have not responded to other treatments. They can be used in combination with other treatments, such as psychotherapy and medication. Brain stimulation therapy should be prescribed and monitored by a healthcare provider with specific training and expertise. A trained medical team performs the procedures. Some brain stimulation therapies like ECT involve using anesthesia to sedate the patient and a muscle relaxant to prevent the body from moving.
SARAH “HOLLY” LISANBY: In this case, an anesthesiologist will monitor breathing, heart rate, and blood pressure throughout the procedure. A treatment plan involving brain stimulation therapy is based on a person's individual needs and medical situation. It usually also includes psychotherapy, medication, or both. Patients will likely be advised to continue these other treatments during and after brain stimulation therapy. Electroconvulsive therapy, or ECT, is a noninvasive procedure that treats serious mental disorders by using an electrical current to induce a seizure in the brain. ECT has the longest history of use for depression and is one of the most widely used brain stimulation therapies. The FDA has cleared ECT to treat severe depressive episodes in people 13 years and older with depression or bipolar disorder. The medical literature also supports the use of ECT to treat medication-resistant schizophrenia, schizoaffective disorder, and mania. ECT is usually considered when a person's illness has not improved after trying other treatments like psychotherapy and medication. To be eligible for ECT, a person usually either has a severe treatment-resistant depression or they require a rapid response due to a life-threatening circumstance.
SARAH “HOLLY” LISANBY: For example, they are catatonic, which is a condition where you are unable to move or respond to the outside world or they are suicidal or malnourished due to their mental disorder. ECT can be effective when medications haven't worked, cannot be tolerated, or are undesirable due to physical illness, which is often the case in older adults. ECT also begins working more rapidly than traditional antidepressant medications, usually taking effect within the first week of treatment. Before a doctor performs ECT, the patient is sedated with a short-acting general anesthetic and given an intravenous muscle relaxant to prevent movement in the body. So the person is asleep for the entire procedure. A typical course of ECT is administered three times a week until a patient's symptoms improve. It usually takes anywhere from six to 12 treatments. Frequently, a patient who undergoes ECT also takes antidepressant or mood-stabilizing medication. Although ECT is effective in treating depressive episodes, follow-up treatment, either antidepressant medication or maintenance ECT or both, is usually required to sustain the clinical improvements and reduce the chances that symptoms return.
SARAH “HOLLY” LISANBY: Maintenance ECT varies depending on the patient's needs and may range from one session a week to one session every few months. The most common side effects associated with ECT include headache, muscle aches, memory loss, and disorientation or confusion. Some patients may experience memory loss, especially for memories around the time of the treatment. Sometimes the memory problems are more severe, but usually they begin to improve over the days and weeks following the end of the ECT course. The risk of memory loss is affected by how the ECT procedure is performed. Two important aspects of ECT technique include electrode placement and pulse width. I'm going to define each of these. Electrode placement describes where on the head the ECT electrodes are placed. The placement of the electrodes on the head determines where in the brain the electric field is induced. The three most common electrode placements are right unilateral, bitemporal, and bifrontal. Of these three electrode placements, right unilateral has the lowest risk of memory loss. Now I'm going to define pulse width, that second aspect of ECT dosing. Pulse width describes how long in milliseconds each electrical pulse lasts.
SARAH “HOLLY” LISANBY: Electrical pulses lasting from one to two milliseconds are referred to as brief pulse. And those lasting from 0.25 to 0.3 milliseconds are referred to as ultrabrief pulse. Of these two pulse widths, ultrabrief pulse width has the lowest risk of memory loss. If you or a loved one needs to have ECT, it's important to talk to the doctor about these two key aspects of ECT dosing. Again, that's electrode placement and pulse width. So you can make informed decisions with your care team about these aspects of your healthcare. If you're interested in learning more about ECT and its history, we invite you to listen to NIMH's Mental Health Matters podcast episode I did recently with NIMH director, Dr. Joshua Gordon. In our lab here at NIMH, we are conducting research studies on ways to make ECTs safer by examining the independent roles that the electric field and the seizure play in determining the efficacy and side effects of ECT. One of our studies, called Transcranial Electric Stimulation Therapy (TEST), for short, delivers an electrical current without inducing a seizure to see if the electrical current itself may be sufficient to treat depression without the seizure. If you want to learn more about the TEST study , we'll share that link in the comments.
SARAH “HOLLY” LISANBY: Now I'm going to move on to talk about another treatment called repetitive transcranial magnetic stimulation, rTMS. rTMS is a noninvasive therapy that uses an electromagnet to stimulate the brain using repeated low-intensity pulses. The magnetic field that rTMS creates is about the same strength as a magnetic resonance imaging scanner, MRI scanner, which is about 2 Tesla. But the magnetic field of rTMS is turned on and off very rapidly. And that rapid change in the magnetic field strength induces weak electrical currents in the brain. These weak electrical currents stimulate the brain cells or neurons and neural circuits in the brain. Several rTMS devices have been cleared to treat specific mental disorders. The FDA cleared the first rTMS device in 2008 for depression in adults who had not responded to at least one antidepressant medication in the current depressive episode. Although ECT is still considered the gold standard for very severe treatment-resistant depression, especially certain subtypes of depression, there's strong clinical evidence supporting the effectiveness of rTMS in reducing depressive symptoms. rTMS is now used to treat moderate to severe depression in cases where medications have proven ineffective or intolerable.
SARAH “HOLLY” LISANBY: In 2008, rTMS was cleared to treat-- or since 2008, rTMS has been cleared to treat several different types of depression, including depression with comorbid anxiety and depression with suicidality. Then, in 2018, the FDA also cleared rTMS for the treatment of severe obsessive-compulsive disorder or OCD. More recently, the FDA cleared a rapidly acting form of accelerated TMS for treatment-resistant depression called SAINT. With the SAINT procedure, patients benefit from having an entire course of treatment in a shorter period of time and getting relief from their symptoms more rapidly. This accelerated treatment involves getting an MRI scan to determine the optimal spot in the front of the brain called the prefrontal cortex for each patient. And just this year, the FDA cleared rTMS for the adjunctive treatment of depression in adolescents 15 years old and up. Rather than applying electricity directly to the head, as we do with ECT, rTMS uses magnetic pulses to stimulate the brain. And these magnetic pulses induce weak electrical currents in targeted regions of the brain. Unlike ECT in which the stimulation is generalized, in rTMS, magnetic stimulation is targeted to specific sites in the brain. Also, in contrast to ECT, rTMS does not require anesthesia, and rTMS can be performed in an outpatient clinic or office setting.
SARAH “HOLLY” LISANBY: A typical rTMS session lasts anywhere from 3 minutes to 40 minutes. A typical course of rTMS treatments consists of daily sessions, five days per week for four to six weeks. Accelerated TMS protocols like SAINT work much faster within a week, in fact. In this case, multiple sessions are delivered on a single day with short breaks in between. We are researching the safest and most effective uses of rTMS, the optimal brain sites to target, and the best follow-up approach to sustain clinical improvement. In our lab at NIMH, we're studying ways to combine TMS with different forms of therapy to make it more effective. If you want to learn more about how to enroll in our rTMS depression studies , we'll share a link in the comments. We are also using TMS to study the brain networks involved in autism spectrum disorders or ASD . And we'll share a link to this study too. If you're interested in what a TMS procedure actually looks like, we'll be sharing a link to an NIMH video in the Facebook comments for you to view. Overall, rTMS is safe and well tolerated. But like all the therapies I'm describing here today, it can have side effects. These side effects of rTMS include discomfort at the site on the head where the TMS coil is placed, contraction or tingling of the scalp, jaw, or face muscles during the procedure, mild headaches or brief lightheadedness, dizziness, and more rarely, seizure.
SARAH “HOLLY” LISANBY: Using magnetic pulses to target a specific brain site results in milder stimulation than we see with ECT avoiding seizure. Although it is possible for TMS to cause a seizure, and a comprehensive review found that the risk of seizure with rTMS is very low, especially when safety guidelines are followed. In fact, most side effects of rTMS appear to be mild and short-term when expert guidelines are followed. Now I'm going to discuss a newer treatment we're studying for depression called magnetic seizure therapy or MST, for short. MST is a noninvasive procedure that uses higher doses of TMS to induce seizures. The seizures are targeted to specific sites in the brain. My team developed MST as a way to make ECT safer by using the minimum amount of electricity needed to induce a seizure and by targeting that seizure more precisely than can be done with conventional ECT. My team and I performed the first MST procedure in 1998, and we used MST to treat the first patient with depression in the year 2000. In the past two decades, my research team and other researchers across the globe have conducted a series of studies on MST showing it to be safer than ECT with less risk of memory loss and yet still carrying antidepressant benefits.
SARAH “HOLLY” LISANBY: In the United States, MST is currently available only as a part of a clinical trial or research study. NIMH has information on joining a clinical trial with MST or other brain stimulation therapies, and we'll add a link to these studies in the comments at the end of our discussion. MST was designed to maintain all of the benefits of ECT but with fewer cognitive side effects, specifically less memory loss. In MST, a magnetic coil is held on the scalp. The magnetic coil induces seizures in the brain that are much more localized and milder than those created with ECT. We do MST under anesthesia, so the person is asleep for the entire procedure. My colleagues and I recently published in the journal, JAMA Psychiatry, a clinical trial of people with severe depression. And we found that these patients showed significant and sustained antidepressant benefits with MST and that it was similar in efficacy to ECT in this study in treating the disorder while leading to fewer cognitive side effects, such as memory problems. However, more confirmatory evidence is needed to draw definitive conclusions about MST's effectiveness in treating depression and other mental disorders. The results of an NIMH-sponsored confirmatory efficacy trial comparing ECT and MST will soon be available.
SARAH “HOLLY” LISANBY: Like ECT, MST carries the risk of side effects caused by anesthesia and the induction of a seizure. These side effects can include headache, dizziness, nausea, muscle aches or fatigue, and memory loss. There are other types of brain stimulation therapy in development, including low-intensity-focused ultrasound, temporal interference, transcranial alternating and transcranial direct current stimulation, and deep brain stimulation, or DBS, for short. I only have time to discuss this last one, DBS. DBS is a surgical implant that uses electricity to directly stimulate sites in the brain. DBS is FDA-cleared to treat severe medication-resistant OCD, and it's being studied in clinical trials for the treatment of severe depression in patients who have not responded to other treatments. DBS works by sending electrical pulses to specific brain areas. It requires surgery to implant the electrodes in the brain. Although the exact mechanisms of action of DBS remain under study, researchers believe that it uses electrical pulses to help reset or modulate malfunctioning networks in the brain. Prior to the procedure, scans of the brain are taken using MRI, which the surgeon uses as a guide to determine where to place electrodes during surgery. DBS was first developed to treat movement disorders, including tremor and Parkinson's disease. The FDA has since cleared DBS for severe OCD.
SARAH “HOLLY” LISANBY: However, there's still much to be learned about optimizing DBS treatment. DBS received breakthrough device designation from the FDA in the year 2022 to investigate its use for treatment-resistant depression. A recent study supported in part by the National Institutes of Health's Brain Initiative showed favorable effects of DBS in treating depressive symptoms. DBS remains an experimental treatment for depression, while more data from high-quality studies such as this are underway. DBS carries risks associated with any brain surgery, such as bleeding and infection. Because the procedure is being studied, other side effects not yet identified are possible. Long-term benefits and side effects are not known. Well, I think this is a good time to stop and take some of your questions. So we're going to pause for a moment and look if you've posted some questions in the chat. And I see a first question here. Is ECT effective for Lewy body disease? Well, thank you for that great question. ECT is effective for a number of neurological conditions. In today's talk, I've focused on the psychiatric conditions that ECT is effective in treating. But also, studies support that ECT can be helpful in certain neurological conditions. For example, movement disorders like Parkinson's disease. ECT is not the primary treatment, but it does have temporary benefit in Parkinson's disease.
SARAH “HOLLY” LISANBY: Lewy body's disease has some similarities to certain forms of Parkinson's disease. Part of why we think ECT might work in such conditions is that it powerfully releases some of the brain's neurotransmitters, which are the chemicals that allow one brain cell to communicate with another. And one of those neurochemicals that ECT releases is called dopamine. And there are certain neurological disorders where dopamine is too low, and Parkinson's is one of those. So now I'm going to look if there's some other questions. Let's see. The next question is, are there ongoing studies on the effect of brain stimulation therapies on schizoaffective disorder? So I did mention that schizoaffective disorder is one of the conditions where there is evidence in the medical literature that ECT might be effective, especially in situations where the medications are not effective. Now, in terms of TMS, the transcranial magnetic stimulation, there is some research looking at whether we could identify the right spot in the brain to stimulate to help with conditions like schizophrenia or schizoaffective disorder. But I would say that we are not yet there in terms of the level of evidence that the FDA would require to demonstrate safety and efficacy. But it is an important area of study.
SARAH “HOLLY” LISANBY: The NIMH does have programs where we support research on novel treatments for schizophrenia and schizoaffective disorder. And the types of treatments that we're investigating include not just brain stimulation therapies but also cognitive and behavioral therapies as well as novel drug treatments. I'm going to look if we have any other questions. Are these therapies safe for children and adolescents as well? So this is a really important question because we know that we are experiencing a youth mental health crisis, and we need more safe and effective treatments for children and adolescents who are suffering from severe mental disorders. That's why it's very exciting that transcranial magnetic stimulation was recently approved to be available for treating adolescents aged 15 years and above. But we know that depression doesn't stop at the age of 15. We know that younger adolescents and even children can experience severe depression. And indeed, death by suicide is one of the leading preventable causes of death in that age group. And so research is underway to try to develop brain stimulation therapies and novel drugs as well as psychotherapies to try to find safe and effective alternatives for younger children.
SARAH “HOLLY” LISANBY: In the case of electroconvulsive therapy, I mentioned that the FDA has cleared ECT down to the age of 13. But we know there are individuals younger than 13 who have serious mental disorders, and that is an area of active research. I'm going to move on to another question here. And the question is, why hasn't my doctor ever mentioned these treatments to me before? So we have a lot of work to do to communicate the latest research developments so that healthcare providers have access to that information so they can provide the latest evidence-based care to their patients. In the case of ECT, this is well-known in the medical literature since it's been around for decades. TMS has been around since 2008. And I would say increasingly, healthcare providers are aware of it. But research has led to more recent developments like the availability of TMS for adolescents and the availability of rapidly acting accelerated TMS protocols. And so events like this and other community outreach events are designed to help communicate and get the word out, both to consumers or individuals suffering from mental disorders that could benefit from it or their family members as well as to clinicians so they can be aware and have access to the most recent developments.
SARAH “HOLLY” LISANBY: So I'm looking at our questions here and I see another question. Are brain stimulation therapies effective for chronic anxiety-based insomnia? So that's another great question. I did mention that the FDA has cleared TMS for the treatment of anxiety when it occurs along with depression. And we know that insomnia is one of the leading signs that a person can have when they have depression. In fact, sleep disturbance is very common in mood disorders. It can be cases of insomnia where you have trouble falling asleep or trouble staying asleep. You can also have hypersomnia where you are sleeping longer than you should and nevertheless feeling fatigued during the day. And so TMS has been found to be effective in treating depression in people with both this combination of anxiety and depression. In terms of whether TMS might be effective specifically for anxiety alone and insomnia associated with anxiety, I would say that's an area for more research. And it's certainly very important because we know that we need more effective treatments for insomnia. One of the important things to know about RTMS in comparison to some medication-based treatments for insomnia, like sedatives or benzodiazepines, TMS is not habit forming. It does not cause addiction and you don't develop tolerance to TMS. But some of the sedative medications that are used to treat anxiety, not all of them but some classes of medications that are used to treat anxiety and insomnia, can be habit forming.
SARAH “HOLLY” LISANBY: You can develop dependence and you can develop tolerance to it, meaning you need a higher dose in the medicine to have the same effect. So we're hopeful that device-based therapies like TMS could be developed to treat a broader range of conditions especially because TMS is not habit forming. You don't develop tolerance to it as far as we know, and you don't develop a dependence on it. Now look here to see if we have a few more questions. I think we have time to answer one more question, and then we're going to wrap up. And I see a question here. Is neurofeedback a more general term for any of these specific treatments, or is it something different? So you're asking a very timely question because NIMH is sponsoring a free workshop tomorrow, May 2nd. We invite you to log in and join us for our workshop on neurofeedback. Neurofeedback refers to a different class of therapies where signals that reflect brain activity. These signals might be derived from electroencephalography, where EEG electrodes are placed on the scalp, or it might be signals derived from functional magnetic resonance imaging or fMRI where you're lying in a scanner and the EEG or the fMRI measures your brain activity and then feeds that back to you with usually a visual cue so that you are able to learn how to modulate your own brain activity and brain network.
SARAH “HOLLY” LISANBY: The brain stimulation therapies that I focused on today are therapies that administer electricity or magnetic fields to the head. Whereas neurofeedback technologies measure brain activity and then present information about that brain activity to the person usually in the form of a computer screen or some sort of visual feedback. So in that way, brain stimulation is different from neurofeedback. But one thing they share in common is they both use devices. One device stimulates the brain, the other device listens into brain activity and feeds that information back to the person so that they can use it to be able to modulate their activity. I really thank you for your questions, and I'm going to wrap us up with a few comments. So we've reached the end of our discussion today. Thank you so much for joining me and for all of your important questions. If you want to learn more about what I've discussed here today, please visit the NIMH website for more information. NIMH sponsors a wide range of research, including clinical trials, to develop new ways to prevent, detect, or treat diseases and conditions. The goal of a clinical trial is to determine if a new treatment or test works and is safe. To learn more or to find a study, please visit our website, nimh.nih.gov/clinicaltrials. Thank you, and stay well.