Hello and welcome. I'm Dr. John Torres, the Director of Digital Psychiatry at Beth Israel Deaconess Medical Center and technology expert for SMI Advisor. I'm pleased that you're joining us for today's SMI Advisor webinar, Electrocursive Therapy, ECT, a Comprehensive Review. SMI Advisor, also known as the Clinical Support System for Serious Mental Illness, is an APA and SAMHSA initiative devoted to helping clinicians implement evidence-based care for those living with serious mental illness. Working with experts from across the SMI clinician community, our interdisciplinary effort has been designed to help you get answers you need to care for your patients. Today's webinar has been designated for one AMA PRA Category 1 credit for Physicians and one Continuing Professional Development Contact Hour for Nursing. Credit for participating in today's webinar will be awarded until available until July 25th of this year 2021. Slides for the presentation are available in the handouts area found in the lower portion of your control panel. Select the link to download the PDF. Feel free to submit your questions throughout the entire presentation by simply typing them into the question area, also found in the lower portion of your control panel. We'll reserve about 10 to 15 minutes at the end of the presentation for question and answer. Now, the most exciting part, I'd like to introduce you to our faculty for today's webinar, Dr. John Roseman. So, Dr. Roseman is the Associate Director for the ECT Service at McLean Hospital, where Dr. Roseman shares oversight of the busiest ECT service in the country that does more than 10,000 ECT treatments per year. He's also the McLean Psychiatry Clerkship Director for Harvard Medical School and the Director of Medical Student Education for Harvard Medical School, helping train medical students at the hospital. As the Psychiatry Clinical Contact Lead for Partners eCare since 2013, he has helped lead the integration of EPIC, electronic medical record software, into inpatient and outpatient psychiatry across partners, and with an ongoing focus on McLean optimization for the EPIC system. In clinical practice, Dr. Roseman focuses on easy treatment for severe depression, bipolar disorder, psychotic disorders, and agitation dementia, while also maintaining a psychodynamically-oriented outpatient practice. Thus, you can see why I'm so excited that we have Dr. Roseman, and thank you for leading today's webinar. All right, well, thank you, Dr. Torres, for the introduction. So, actually, since submitting my bio for this webinar, I actually have acquired one more position, which is I'm actually also now the Medical Director of the Transcranial Magnetic Stimulation Service, or TMS, at McLean as well, so a little change in roles. As far as disclosures, I have no financial relationships or conflicts of interest to report for this webinar, and so just jumping right into it. So, the learning objectives for today. So, my hope is that at the end of this webinar, you all will be able to readily identify patients who are appropriate for ECT, be able to describe different techniques that we use to decrease the memory and cognitive side effects of ECT, and then summarize options for maintaining ECT response after an initial acute course of ECT. So, what I'll be doing is I'll start by giving you a little history, a brief history of ECT, a discussion of who gets ECT and indications for use, how we actually perform the technique or the procedure, how we reduce the memory and cognitive effects of ECT, how we maintain the gains that we achieve during the treatment, what little we know of the mechanism of actions, and then some common misconceptions about ECT. So, jumping right in, so what is ECT? ECT stands for electroconvulsive therapy, also known as electric shock therapy. It's a medical procedure that's performed under general anesthesia, so the patient is asleep for a few minutes for the entire procedure and also given a muscle relaxant or paralytic to prevent a significant motor convulsion during the seizure itself. To do the treatment, we use a very brief, very controlled, and low-power electrical stimulus. It's administered for up to eight seconds with the modern machines and induces a short seizure that usually lasts less than one minute and then spontaneously ends. The stimulus can be on one side, unilateral, or both sides, bilateral, and we'll get into discussion of the differences later on. It's very safe and it's painless. The biggest physical complaint that we'll get from patients is occasional headaches or jaw pain post-treatment, really of the degree that can be easily treated with Tylenol or ibuprofen, and the treatment itself is very quick. It really lasts only minutes and patients can return home after a couple hours after outpatient treatment. To give you a very brief history of the origins of ECT, in 1934, a Hungarian psychiatrist and neuropathologist, Ladislas Meduna, I'm probably mispronouncing his name, he observed on post-mortem that the brains of patients who had epilepsy had more glial cells and patients who had schizophrenia had fewer glial cells, so he hypothesized that there might be something actually protective about seizures and that perhaps one could treat schizophrenia by inducing seizures. He tried this with a 33-year-old patient who had been catatonic for four years and used an intravenous injection of camphor to induce seizures, but after five or six of these seizures, the patient became responsive and was able to speak and walk and care for himself. So, the problem with intravenously-induced seizures is that they were inefficient and very uncomfortable for patients. It was unpredictable when exactly the seizure would take place. It could take minutes before the medication had its effect, and patients would describe feeling terrible before the seizure as having these senses of impending doom or terrifying fear before the seizure began, and different chemical agents were tried. One common one was called metrazole, which has this longer, unpronounceable chemical name, and the effects were similar with also the same downsides of unpredictability and slow onset. So, in 1938, two Italian psychiatrists, D'Ugo Cialetti and Lucio Binni, thought to try using electricity to induce seizures. They had been studying epilepsy in dogs using electricity to induce seizures in the dogs, and they thought to apply this method in a person. They chose a 39-year-old man who had disorganized schizophrenia and had been found wandering in a train station, and after several ECT treatments, his psychosis improved, and he was able to return home to his wife and his job in the community. So, the big advantage of using electricity is that it was much quicker onset, much more predictable onset, and it really had fewer side effects. So, on the whole, it was much more tolerable for patients, and the use spread quite quickly throughout Europe. In 1940, ECT came to the United States, and by 1941, it was being performed at McLean Hospital, and I just want to draw your attention to this photo at the bottom. This is from the McLean archives showing one of the early ECT devices. Interesting, down here is the on and off switch, and that was how the psychiatrists would control the duration of stimulus. They'd turn it on and then shut it off when they felt that inadequate stimulus had been given. Modern machines obviously have much greater control than this device. One of the big advances to ECT took place in the early 1940s with the use of barbiturates for anesthesia to induce anesthesia for the patients, and then the use of curare as a paralytic agent to actually prevent a motor convulsion during the seizure. This made ECT much, much safer for patients, since actually the motor convulsion was really the most dangerous part of getting ECT. Patients could dislocate joints or even break bones during a violent seizure. In 1949, unilateral ECT was introduced. It had previously been bitemporal or bilateral, and this was done to reduce the electrical current going through speech centers and reduce memory effects for ECT. In 1952, succinylcholine replaced curare as the paralyzing agent, and succinylcholine is a depolarizing paralytic. A big advantage of this medication is that it essentially reverses itself. After about three minutes of paralysis, the patient will spontaneously begin breathing again. In the U.S. and from the 1960s to the 1980s, ECT really fell out of favor and its use declined. The reasons for this are not entirely clear, but a lot of it had to do, we think, with the way ECT was viewed in the popular imagination, which was influenced, at least to some degree, by the publication of the book and the release of the movie of One Flew Over the Cuckoo's Nest. For those of you who have seen it, it really portrayed ECT as kind of a barbaric and punitive treatment that was really just the side of lobotomy. In the 1990s, ECT really began to make a resurgence and has been really used more regularly since that time, becoming more accepted, I think, because of a reduction in stigma, better public education, and also improved treatments that the treatments are now much more benign and better tolerated, and also better informed consent. Then the biggest change to ECT in the last 20 years has been the introduction of what's called ultra-brief pulse ECT. I'll talk more about that later, but it's a change to the treatment that has made it much, much more tolerable with fewer memory and cognitive side effects. Why do we use this technique that's been around for almost 100 years? Essentially, ECT is by far the most effective treatment that we have in psychiatry for the treatment of depression and other major mental illnesses. It's very effective for patients who have shown medication resistance or who are tolerant to medication, and it's very effective for patients for whom the severity of illness is so extreme that they really need very, very rapid response. We look at who gets ECT. In the United States, there actually have been very few studies of the demographics of ECT patients, but whatever studies have been done have shown that, in general, patients who receive ECT are more likely to be female, elderly, and white. In a large study of inpatients, elderly Black and non-Hispanic patients with depression diagnosis were about half as likely to receive ECT as a white patient. Studies in Texas show that there were significantly higher treatment of white patients, the lowest treatment among Latino, Latina patients, with ECT generally underused among Black, Latino, Latina, and Asian patients. The same really was true in community hospital studies as well, which showed that even in hospitals with similar availability of ECT, Black patients were much less likely to receive ECT than white patients, 7% versus 2%. We don't really know why there are these disparities, and that really is an area for a future study. It probably has something to do with stigma, cultural belief, provider knowledge of ECT, which hopefully webinars like this will help improve that provider knowledge, issues of access to care, and then also bias in diagnosis. It's really well known that Black patients are more likely to be diagnosed with schizophrenia than white patients. If you're diagnosed with schizophrenia as opposed to depression with psychosis, you're much less likely to be prescribed ECT as your treatment of choice. Currently, there's a paper in submission from McLean Hospital where we're looking at data on patients who self-identify as gender non-binary. It's actually a pretty small group of patients. It's 17 patients, but at least these are areas that are being studied. Now, I'm going to move on to some case examples to illustrate the different indications for the use of ECT. These are all cases that are drawn from patients that we have treated at McLean Hospital over the last probably decade or so. The first patient, a married white man in his 70s. He had no previous history of psychiatric illness until his retirement, but soon after he retired, he began to become depressed, and it progressively worsened over the next several years. He'd had trials of multiple medications, including SSRIs and other classes, antipsychotics, and also a tricyclic amphetamine without any benefit. In the two years prior to his admission, he developed anhedonia, anergia, insomnia, and poor appetite, so a lot of neurovegetative symptoms, and then also psychosis with paranoid delusions and also inability to care for himself, so he would soil himself repeatedly rather than get up to use the bathroom. ECT is used in cases of psychotic depression very frequently and really could be considered one of the first-line treatments for this condition. It's been found that psychotically depressed patients probably respond faster than non-psychotic patients, and in the study by Petrides, where he looked at 253 patients being treated with bilateral ECT, he found remission rates as high as 95%, so very high remission rates for psychotic depression. ECT has been found to be at least as effective as combination medication therapy and probably more effective than combination med therapy in elderly patients. For patients who have catatonic symptoms, the ECT is extremely effective with efficacy rates in the 80-100% range, and it really should be considered as a first-line treatment in any time there's very severe catatonia, like malignant catatonia, severe catatonic excitement, or any time that benzodiazepines, which are the other standard treatment for catatonia, have failed or really any time that the patient is so ill that really rapid resolution of symptoms is required, so in the treatment of major depression, no trial has ever found any medication to be superior in efficacy to ECT. Response ranges for medication-resistant patients is in the range of 50% to 60%. In medication-naive or medication-intolerant patients, the response rates can be 80% to 90%, so really very high response rates, and the elderly in general probably have higher response rates than the general population. So moving on to another case example, in this case we had a married white woman in her mid-30s. She was a high-functioning healthcare professional with a history of bipolar 2 and has had a history of a remote hypomanic episode that had lasted nine months. She had had two previous depressive episodes, but the episode during which she came to ECT was the worst, and it had lasted four years since the birth of her daughter, and she had a history of two prior suicide attempts. She was admitted to the hospital for suicidal thinking, severe anxiety, guilt, poor energy, a 13-pound weight loss over the month prior to admission, and poor concentration and functioning, and she had been hospitalized a month prior for similar symptoms. The patient had just completed a partial program, but she was unable to work, was not functioning well, and was very worried about losing her job. At the time of her admission, she was on venlafaxine and eripiprazole, which had helped in the past, and she'd been on them for years. No other documented med trials, although she thought that she had been on an SSRI and sometime in the remote past. The admitting team had recommended either starting her on lithium, lamotrigine, or trying ECT, and so we were consulted. This patient had bipolar depression, and ECT is also extremely effective for bipolar depression. This meta-analysis of six studies in 2012 found that ECT was equally effective for both unipolar and bipolar depression, and a randomized controlled trial in 2015 compared ECT to the Goodwin-Jameson medication algorithm. For those of you who are not familiar with it, the Goodwin-Jameson algorithm is one of the recognized treatment algorithms for bipolar depression. It's not the only algorithm, but it is a recognized and accepted algorithm. What they found in the study of comparing ECT to medication was that the remission rates were essentially the same. There was no significant difference. It was about 30% for both ECT and medication. However, the response rates were much higher for ECT at 74% for ECT versus 35% for medication. There was also a non-significant shorter time to response in the ECT group. Actually, these response rates were among patients who had actually completed the treatment. The next case, the case of a 47-year-old man with bipolar I who had recently been discharged from the hospital for mania and psychosis, and then was readmitted from his residential facility for an increase in disorganized behavior and paranoia and also not taking his medications. On his presentation back at McLean, he was pressured, hyperverbal, hypergraphic, and showed very poor concentration. He became psychotically preoccupied with the belief that the treatment team wanted to kill him and were trying to kill him with medications, and so he was declining all medication treatment. His symptoms progressed to delirious mania, which was characterized by disorganized thinking, disorientation, confusion, memory impairment, and grossly disorganized behavior. For example, he was smearing feces on himself, including on his face. Ultimately, the treatment team went to court for the right to treat, and they included ECT as part of the treatment plan. This is really a case of a patient in a psychotic manic or mixed state. Technically, this is an off-label use of ECT, even though that's not really quite the right term. Some of you may know that in 2018, the FDA reclassified ECT devices for the treatment, specifically of catatonia and severe unipolar or bipolar depression. They reclassified the devices from class III, which was considered higher risk, to class II, which was moderate risk. For any other use of ECT devices, including schizoaffective disorder or bipolar manic states, the FDA requires what's called a premarket approval application, which is the most stringent type of device marketing application for class III devices. In practice, we use ECT all the time for mixed or manic states, but again, effectively, for its classification to a class II device, it's really indicated for catatonia and depression. Anyway, a recent large review of 115 publications over the last 80 years showed that ECT was highly effective for treating acute mania with comparable or even superior rates to those obtained with psychopharmacology. The study also found that there was strong efficacy for the treatment of mixed states, especially for medication-resistant episodes. Because of heterogeneity in these studies and the lack of randomized controlled trials, it was difficult for the authors to make any real conclusions beyond that, but in any event, ECT was found in these meta-analyses to be effective for mania and mixed states. For delirious mania, ECT really should be considered a first-line treatment. For those of you unfamiliar with delirious mania, there is some controversy over whether or not it exists as a syndrome and a claim where we're kind of true believers in delirious mania. It lacks a formal diagnostic classification, but is really this life-threatening syndrome that's characterized by manic symptoms, psychosis, disorientation, fluctuating levels of consciousness, which is characteristic of a delirium. And we see it in anywhere from 15 to 35% of acutely manic patients. And these patients can also show some catatonic symptoms. Delirious mania is a really very serious condition, and if it's unrecognized or if it's improperly treated, it can progress rapidly. And really can become a life-threatening illness. There is a lack of controlled trials of ECT for delirious mania, but numerous reports have shown efficacy. And at McLean Hospital, we have extensive experience treating patients with delirious mania. And it really results in very rapid symptomatic improvement. Delirium can resolve in as quickly as one or two treatments. Usually see resolution of psychomotor excitement within two to four treatments, and often can see a full resolution of the delirious mania in six treatments. So very, very rapid and very effective for this life-threatening condition. So looking at other indications, for schizophrenia, ECT has been used and will be used, and it's relatively effective. And there are predictors of good response for patients with schizophrenia. Patients who have abrupt or recent onset of their illness, if they have catatonic symptoms, since catatonia is so exquisitely sensitive to ECT, if they have a history of favorable previous response to ECT, if they're in the midst of a psychotic exacerbation of short duration, if they have less consistent preoccupation with delusions and hallucinations, so sort of less of an entrenched kind of psychosis, and fewer schizoid and paranoid pre-morbid personality traits. These are all predictors of a good response for patients with schizophrenia. Other indications of schizoaffective disorder, which obviously has that affective component, and also treatment-resistant schizophrenia, particularly clozapine-resistant schizophrenia. What we find in clinical practice is that patients can often have a significant reduction in their psychotic symptoms from ECT. Often it's difficult to get that response to last. So a patient may do better for maybe two weeks, but then symptoms will start to creep back in, and repeated treatment is often needed. It seems that bifrontal placement, and we'll talk more about placement soon, that bifrontal placement may have a superior clinical and cognitive outcome in patients with schizophrenia, at least compared to bilateral patients. And this study from 2013 looked at a memory scale that was actually an instrument used in India, and patients with bifrontal treatment actually had higher scores on this memory scale, and overall superior performance in cognitive measures when they were treated with a bifrontal as opposed to a bilateral treatment. So the last indication for ECT is decidedly off-label, but is actually very effective. It's the use of ECT for patients with dementia and behavioral disturbance or aggression. And this is a research interest at McLean Hospital in the ECT department, and in our geriatric psychiatry department. McLean has published a retrospective study back in 2012, and also a prospective naturalistic study in 2015, looking at patients who had dementia and behavioral disturbance, and really found that the treatment was very effective for improving these behavioral disturbances. Currently, McLean is part of a multimillion dollar grant for a large multicenter perspective control study, which is underway right now. So we look at this graph, which comes out of that 2015 study. It's looking at scores on the NPI. The NPI is the neuropsychiatric inventory, the nursing home version. And what this is, is a comprehensive assessment of psychopathology in patients who have dementia and who are residing in nursing homes. So this was the measure that was used in the study. And if you look in all these different domains of behavioral discontrol, agitation, psychosis, and mood symptoms, patients showed a significant improvement in symptoms over the course of their ECT treatment. So starting with baseline to treatment 12. So it showed that the treatment was very effective for treating these behavioral disturbances. The clinical global impression scores on average also changed from a rating of markedly agitated or aggressive at baseline to borderline agitated slash aggressive at discharge. So some improvement. There was also no worsening of the patient's actual dementia symptoms. So it didn't really have any kind of, it didn't cause any further cognitive decline, but did show these improvements. All right, so moving on to how ECT itself is done. So I've thrown around the terms of bilateral and unilateral and bifrontal. So now we're gonna talk a little bit more about what that means. So for bilateral treatment or bi-temporal, we're placing the ECT electrodes symmetrically on either side of the head, essentially near the temple. We're looking for a line from the corner of the eye to the external auditory meatus, and we're going up two to three centimeters. And that's the point at which you put the center of the ECT electrode. And again, you're doing the same placement symmetrically on the other side of the head. The big advantage for bilateral or bi-temporal treatment is probably quicker response and better efficacy. The biggest disadvantage is that patients do tend to have more memory and cognitive effect from bilateral treatment. For unilateral treatment, the electrode on the side of the head is placed as in bilateral, and the other electrode is placed essentially at the vertex of the head, just slightly to the right of midline. And this is for right unilateral treatment. Big advantage of this placement is really less memory and cognitive side effect. The disadvantage is it may work more slowly than bilateral and may require more treatments, but at high power can really approximate the effectiveness of bilateral. The last standard placement we use is bifrontal, where we're basically moving the electrodes from the side of the head up to the corners of the forehead, looking for five centimeters above the corner of the eye. Cognitive effects for bifrontal are likely somewhere in between unilateral and bilateral treatment. And we'll often do this when unilateral is not effective, but for some reason bilateral is either not well tolerated or just it's not desired. And if you think about it, when you're moving the electrodes up onto the forehead, you're getting farther away from the temporal lobe, sending less charge through hippocampus and through speech centers. So you get less memory impairment in general with bifrontal. And these are pictures I like. This is Voltaire. This was Edgar Allen Poe who probably suffered from depression. So it's an appropriate person to have here. So a little bit more about how we perform ECT itself. So on the very first treatment, we are doing what's called a titration. We're essentially finding the minimum charge needed to induce a seizure. And we begin at a very low charge and keep on bumping up the settings until we obtain the seizure. For the subsequent treatments, when the patient returns for treatment number two, for unilateral, we go to four to six times seizure threshold more typically six times seizure threshold. If a patient is getting bilateral treatment, we go to one and a half to two times seizure threshold or alternatively we can use the half age method. In the half age method, you take the patient's age, you divide it in half and you use that as a percentage of the overall maximal charge of the machine to find your setting. So for instance, a 50 year old patient, half age 25. So we need to set the machine for 25% of its maximal charge setting. And typically that half age setting ends up being very close to the one and a half to two times seizure threshold that we would find with a titration. Initially ECT is given three times a week to start or two if there's a high risk for memory loss or confusion. For instance, a patient perhaps who's had a traumatic brain injury and comes in with a baseline cognitive issues, we may start with a lower frequency of treatment. And in typical acute courses, usually in the range of eight to 15 treatments, which is then followed by a taper phase of the patient response to ECT. So now moving on to the side effects. Memory loss is the side effect that patients are most concerned about, patients and their families are most concerned about when they undergo ECT. And memory loss can really vary very greatly among different patients. It's very dependent on the electrode placement, the bilateral versus unilateral versus bifrontal, how frequently we're giving the treatments, the overall number of treatments and then the electrical charge. Those are all things that can affect the degree of memory impairment. However, also the severity of the underlying illness and patient factors are also important. As all of us who treat patients with depression or other illnesses know, depression in and of itself can impair memory and cognition. Typically the memory deficits are very manageable and they usually resolve quite quickly actually over time once ECT is finished. However, patients will frequently still have some gaps in memory from the period during their treatment or even just prior to the acute course. Less commonly gaps in memory can persist for more remote memories, although that tends to happen more with more aggressive treatments like bilateral. So when we meet with patients and talk to them about ECT, we do instruct them to expect some short term memory loss from the time that they're getting treatment and we really advise them to avoid any major life decisions during the acute course just because of the potential for memory problems. So memory effects in ECT have been studied quite extensively. Actually, if you think about memory, we usually think in terms of integrated memory, which is that ability to form new memories and then also retrograde memory, which is more like autobiographical memory or the ability to recall past memories. In studies of intergrade memory, they found that really the effects from ECT are not long lasting. There was this large review in 2010 that looked at almost 3000 patients in a meta-analysis, which found, and I'm quoting from the paper, that cognitive abnormalities associated with ECT are mainly limited to the first three days post-treatment. Pre-treatment functioning levels are subsequently recovered. After 15 days, processing speed, working memory, intergrade memory, and some aspects of executive function improved beyond baseline levels. So the take home of that is that there definitely are cognitive and memory issues immediately after treatment, but within two weeks or after two weeks of treatment, those memory deficits resolve and that in some domains you actually see an improvement of memory and cognitive functioning. And that's mirrored by our clinical experience as well. And so there really is no evidence of any long-term effects on that intergrade memory. So retrograde memory is a little bit harder to study. It's difficult to measure and can be influenced by a lot of other factors, but a large naturalistic study that was done by Harold Sackheim, whose name you'll see repeatedly over the remainder of this talk, they looked at bilateral treatment versus unilateral treatment, and they found that bilateral treatment was significantly more associated with sustained autobiographical memory effects, six months post-treatment. So if you look at this graph that came out of the Sackheim study, all these bars here, these are different neuropsychiatric measures and tests. So they're measuring different domains of cognitive and memory functioning. What I really would like to draw your attention to is just the last grouping here. So this is the AMI, which the autobiographical memory interviewed. So it's a test of retrograde memory by looking at autobiographical memory. And what you see here is this white bar, which is unilateral treatment, that at six months, the patients have no further deficit in autobiographical memory, whereas with the bilateral patients, they still do have some ongoing deficits six months post. The gray bar is bilateral. The black bar is sine wave ECT, which is actually an electrical waveform that we no longer use in ECT devices. So that's not really relevant, but the main things to focus on are the unilateral versus bilateral. All right, so to talk a little more specifically about what's going on with our ECT machine, we have to talk about kind of what's new or relatively new in ECT. So this represents the electrical waveform that's produced by modern ECT machines. As I mentioned before, older machines used a sine wave, but that's not used anymore. The modern machines use this electrical square wave. We can change a lot of parameters when we're doing treatments. We can change the duration of the stimulus, so just how long we give it. We can adjust the frequency, so the number of these pulses per second. We can adjust the current, which for different machines, one machine, the default is 800 milliamps. For a different brand of machine, it's 900 milliamps. That's something we typically don't change, but it can be changed on these machines. And then the last thing we can do is we can actually alter the duration of the electrical pulse itself. We call it a pulse width, even though it's a time. When we talk about standard pulse or brief pulse treatment, we're talking about a pulse with a 0.5 or one millisecond. With some of the older machines, we would do wider pulse widths, so one and a half or even two milliseconds. In the last 15 years, ever since 2018, we've been doing what's called ultra-brief pulse, where the pulse width is 0.3 milliseconds. The idea behind ultra-brief pulse is to take advantage of the optimal depolarization time of a neuron, which is 0.1 to 0.2 milliseconds. So if you think about it, with this wider or longer pulse, during that pulse, you're trying to stimulate neurons that are in a refractory period, because they've just been stimulated. They cannot be re-stimulated. If you're doing this series of much more rapid pulses, you're essentially able to obtain a seizure in much lower charge settings, so you can obtain the seizure much more efficiently. And with the lower charge, patients tend to have a lot less in the way of memory impairment from the treatments. So in this pivotal study that Harold Sackheim did in 2008, looking at ultra-brief pulse, what he and his co-authors found was that ultra-brief pulse unilateral treatments worked as well as brief pulse treatments, both bilateral and unilateral, but had much less retrograde memory loss. They did find, however, that ultra-brief pulse bilateral did not work very well, and they hypothesized that if you needed to turn the ultra-brief pulse up high enough to make it effective in bilateral, you would probably lose any benefits of it, so they didn't really study it further or recommend doing ultra-brief bilateral. At McLean, we have extensive experience using ultra-brief pulse unilateral, and we also have noted a significant difference or improvement in cognitive and memory effects when we use ultra-brief versus brief pulse unilateral, or certainly ultra-brief unilateral versus bilateral treatment. So this graph is from that Sackheim paper, where if you look at the orangish-red bar is ultra-brief pulse. If you look at immediately post-randomization course of ECT, so this is after an index course of ECT, and at two months and six months, you see much less of a deficit in autobiographical memory when using ultra-brief pulse unilateral. So you often see in brief pulse unilateral and also in bilateral, you see significantly more deficit. This bar, the checkered bar, are patients who crossed over from unilateral or ultra-brief treatment to bilateral if they were not having a response during the initial course. But really the take-home message is, if you look at ultra-brief pulse, you see much less deficit in autobiographical memory or retrograde memory when you use ultra-brief ECT. Okay, so now to go on to how we do ECT, particularly at McLean Hospital, but this is pretty representative of how most centers will proceed. As I mentioned previously, the very first treatment, we titrate to seizure threshold. We will typically begin patients with right unilateral ultra-brief pulse. With the following two treatments, we then remain with right unilateral ultra-brief moving up to six times seizure threshold. For treatments four to six, if the patient is improving, we just continue what we're doing or perhaps make minor increases in the settings just to basically increase the dose slightly if there's some improvement, but not as much as we would hope. If the patient is really not showing improvement, then we can further increase the ultra-brief settings to eight to 12 times seizure threshold. In treatments seven to nine, if the patient's improving, we just keep doing what we're doing. If there's little or no improvements despite adjustments to the ultra-brief, we may consider switching to brief pulse unilateral typically with a pulse width of 0.5 or sometimes one, generally at about 75% power. As we continue, if we're, again, improving, we don't change anything. If the patient is not improving with the unilateral, at this point, we may consider switching to either bifrontal or bilateral. And which we choose is really based on the tolerance of treatment and clinical situation. Generally, when we make this switch to a bilateral or bifrontal, we'll start with the slightly less aggressive pulse width of 0.5 and usually estimate using that half-age method that I've mentioned before, or else we could retitrate and then use a two-time seizure threshold for the subsequent treatment. For treatments 13 to 15, if the patient is improved or has improved, we'll either continue the current parameters or actually we'll start to taper the frequency of treatment at that point. If the patient is not improving, we may increase the bilateral pulse width from 0.5 to one or increase settings. We could also switch to bilateral if we had got to bifrontal. So the basic idea is if the patient's doing well, you keep doing what you're doing. If not, then we kind of move up the ladder of increasingly aggressive treatment until we get a good response. This is really just a basic algorithm, though, and we will adjust it based on our clinical experience and clinical situation. For example, if we're dealing with a patient who has catatonia, malignant catatonia, delirious mania, those patients will often start immediately with bilateral treatment, just given the urgency of the situation, since we know that bilateral is pretty much guaranteed to work with these patients. Once they've improved, we can often back off and switch them to unilateral to minimize memory or cognitive issues once the most acute aspect of the illness has been resolved. If a patient isn't tolerating right unilateral brief pulse, we can always go back to right unilateral ultra brief, but just go into a higher charge or perhaps spreading out the treatment if they're having a lot of memory issues. And if a patient has not responded to unilateral treatment and they can't tolerate bilateral, as I mentioned, we might go to bifrontal placement. So then there's the question of what do you do after you've got somebody better with ECP? We really recommend some form of maintenance treatment, either ECP or pharmacology or both. And when there've been studies of looking at relapse rates following ECT, patients who are medication resistant seem to have higher relapse rates after ECT, which is not surprising since those patients are often ones with the most difficult to treat illness and probably more likely to relapse in general. In this study, another study by Harold Sackheim from 2001, he looked at, he and his co-authors looked at patients who had remitted with ECT over a 24-week period post-treatment. And these were patients who had been medication-resistant or had psychotic depression. And they looked at a group with placebo. Those patients showed an 84% relapse rate. Patients who were started on nortriptyline alone had a 60% relapse rate. And patients who were started on a combination of nortriptyline and lithium had a relapse rate of 39%. All of those relapse rates are rather high, but some of that had to do with the design of the study. For instance, these patients were completely off of medications during ECT and were not started on these medications until after the acute course of treatment had taken place. But the take-home was that if you don't give the patient something after ECT, the risk of relapse is really very high. So we will typically advise our patients to either switch or augment their antidepressant following ECT if the pre-ECT regimen had not been enough to keep them well. And we will sometimes switch patients over to MAOIs, often using the period of ECT as the washout. So essentially they are protected or helped. Their depression is managed by the ECT during that period of time when they're washing out from their previous antidepressant treatment. What we'll typically do is after we complete ECT is our recommendation is that patients will do a continuation phase, which the goal of that is to prolong the beneficial effect of the acute course. Initially, we'll have patients return for weekly treatments that will typically go from anywhere from two to four weeks, depending on patient response. And then we taper a week at a time as tolerated, but we remain flexible. So if a patient has a worsening of symptoms, we can always make the treatments a little more frequent, or if they're doing extremely well, we may accelerate the rate of the taper. Once the patients are stable without any relapse of symptoms for either monthly or perhaps a greater interval, typically we'll stop ECT, but this is usually done in combination with medication. So we're trying to optimize their medication treatment during this time of taper so that they're well protected when the ECT finally stops. A small proportion of our patients do go into indefinite maintenance, which means treatments somewhere in the range of two to really out to eight weeks or sometimes even further. And those patients may indefinitely remain in the ECT treatment, adjusting the interval between treatments based on clinical response, but typically indefinitely doesn't mean forever. So after a few years of maintenance, often patients will try to stop and see how they do, and some of them will do perfectly well. So the question of continuation ECT versus continuation pharmacology has been studied by the core group, which is the Consortium for Research in ECT. This study compared patients in a structured continuation ECT series of 10 treatments comparing to continuation pharmacology with nortriptyline and lithium. And this study was designed to be similar to the Sacheim study where he was looking at placebo, nortriptyline and nortriptyline plus lithium. So that's what this medication was chosen. They looked at 201 patients that were depressed and were remitted with bilateral ECT. So what they found in six month follow-up was essentially that the ECT and the pharmacology groups had essentially the same rates of relapse, dropout and remission. And there was really no statistically significant difference among the groups. So what it tells us though, is that ECT continuation is really as good as psychopharmacology for continuation. In this further study, the PRIDE study, so this is Prolonging Remission in Depressed Elderly, which was in the American Journal of Psychiatry in 2016. The study looked at the use of ultra-brief pulse, unilateral ECT combined with dental vaccine in elderly depressed patients to look at remission rates. And what they found in phase one was the ECT only part. And they found that the remission rates for these patients were 61% and 70% response rate. They took the patients who were remitted and then enroll those who wanted in phase two, where they compare the medication of dental vaccine plus lithium versus medications with flexible dose ECT continuation. And flexible dose is kind of what I described here, what we do in clinical practice where the ECT dosing is really based upon clinical response. What they found is that overall the response, the relapse rates were very low, only 16.7% of patients relapsed, but the odds of relapsing were 1.7 times higher without ECT. And the odds of being rated not ill at all on the CGI, which is the clinical global impression scale were 5.2 times greater if continuation ECT was added to the medication. So greater chance that you will be not ill at all if you had get ECT. And these are the studies that really have guided us on our decisions to recommend maintenance and continuation treatment. So the take home points of maintenance is that most patients really do require some kind of maintenance to prevent a relapse of their illness. We recommend a continuation taper for patients who have responded in addition to optimizing medication. If a medication didn't work before ECT, then consider switching or augmenting. If the illness was a breakthrough depression for a patient who had been on a stable regimen that had previously been very successful, often we'll recommend just bumping up the dose of that medication or augmenting. And if the patient is unable to maintain the gains from ECT, meaning that as we start to do the continuation phase where we're tapering, their mood continues to decline, then we often will consider a lithium augmentation or possibly switching them over to an MAOI, which a lot of patients have not previously tried. We also strongly recommend to all our patients that they engage in psychotherapy just to help deal with just the trauma of having been that ill and reconnect with supports and deal with the losses that they experienced from their illness and also help identify and prevent triggers for relapse of their illness. All right, so I'm going to briefly talk about what we know about the mechanism of ECT. And I think the take home of the next couple of slides is that we're not exactly sure how ECT works, but we know that it works on many different systems and aspects of the brain. So ECT definitely affects regional cerebral blood flow and brain metabolism. We know that there's definitely an anti-convulsant effect to the brain kind of repeatedly shutting down the seizures. And this increased GABA inhibitory response is felt to also be involved in the beneficial effects of ECT. There may be some element of kind of rebooting the diencephalon or those deeper structures of the brain since we'll often see a pretty rapid correction of like sleep-wake cycle disturbances or appetite. There are also neuroendocrine effects. You get a flood of different neurotransmitters anytime you have a seizure. So there's an effect on neurotransmitters. And then there's also an effect on neurogenesis and neuroplasticity that you get alterations and growth factors such as the brain-derived neurotrophic factor. And this next slide, this comes from a researcher at McLean Hospital who actually developed a mouse model for ECT. So she actually has devised an electrical stimulation for mice and found that there was an increase in hippocampal neurogenesis, BDNF, and brain transcription in the brains of mice who are treated with this mouse model of ECT. So we've also found that ketamine also has similar effects on the brain, which suggests, and ketamine is another treatment that we're using for depression in the neurotherapeutics department at McLean. And it suggests that a lot of our different neurotherapeutics may have some common pathway, which is why perhaps they all work. But anyway, just a quick look at what we know about ECT and how it works. All right, so next thing that I think very important to talk about are just myths or common misconceptions that patients will come to ECT with. So I often will get the question of, will ECT cause dementia or brain damage? And there has been no association found between getting ECT and developing cognitive impairment later in life. If anything, ECT has been associated with volumetric enlargements in parts of the brain. So I think the take-home is that if anything, it probably encourages the brain to heal and to grow and grow new synaptic connections. It's not causing any kind of damage to the brain. People worry that ECT will cause a stroke. There is a transient increase in intracranial pressure during the ECT treatment, but there is no association with any elevated risk of either recurrent or incident stroke. However, as a precaution, we recommend that patients wait at least six weeks after a stroke before they begin ECT. Patients ask if they will develop seizures, will they get epilepsy because they're having seizures induced? And ECT has not been found to cause epilepsy at any retrospective studies, although there are isolated case reports of development of seizure disorders in patients who underwent ECT. And then one large study found a weak positive association between ECT and subsequent epilepsy in patients younger than 40, but a negative association in patients greater than 40. So the authors really felt that you just couldn't draw any definitive conclusions. So if it's any comfort to patients, ECT is also used to treat refractory status epilepticus so that it can actually be used to break seizures. And then finally, patients ask very reasonably, will they die during treatment? It is extremely low risk. A large European study that looked at almost 800,000 ECT treatments found that the ECT related mortality was 2.1 for 100,000 treatments. And these authors actually felt that that was quite a conservative estimate. It was probably much lower than that. And they noted that the risk of death during ECT was actually lower than the risk of anesthesia independent of the ECT. So take home is it's extremely safe. So I just threw a lot at you, but the conclusions, ECT, it can be lifesaving. It should really be considered as a first-line treatment for catatonia or psychotic depression or any time that a really quick response is needed. Advances to ECT have made it much safer, much more comfortable, and with a much better cognitive and memory side effect profile, which has really allowed it to be used as just a good treatment among others as opposed to a treatment of last resort. And any patient who undergoes ECT really does need some kind of plan for maintenance, either pharmacologic or ongoing ECT, and that should really be considered right from the beginning of treatment. All right, thank you very much for your attention. Thank you so much for interesting presentation, Dr. Rosen. That was so much just valuable information. Before we shift to the question and answer, I want to take a moment and let everyone know about the SMI advisor that were actually accessible via a smartphone app. You can use the SMI advisor app to access resources, education, upcoming events, complete mental health rating scales, and you can submit questions directly to our team of SMI experts. You can download the app at smiadvisor.org slash app. So we'll go next slide into our question and answer. And what's fantastic is your last slides actually answered some of the questions. So some of the ones that weren't kind of in those rapid-fire points at the end is you were noting that you kind of augment ECT with psychotherapy. Is there any type of psychotherapy or preference of what therapy you use in addition to ECT, with ECT? Often we just recommend that the patients do whatever they feel is most beneficial for them, because I think some patients really engage very well in a more of a psychodynamic therapy, really just to kind of help them process having been so ill and the losses they've experienced. But generally speaking, we'll also recommend that they consider doing something more like CBT or DBT to really help more specifically with the depressive symptoms. So kind of a long-winded way of saying we don't have any specific recommendation. We kind of recommend whatever works well for that patient, but it is not infrequent for us to recommend that a patient at least try CBT if that's something that they haven't tried previously. That makes sense. And this is a different question saying you talked about ultra-brief and brief. So if ultra-brief is effective and has less side effects, why would people wanna use brief pulse? So clearly there's more to it than just that pulse-width diagram that I showed you, because for some patients, ultra-brief just doesn't get them better, and yet brief pulse does. And so we'll switch simply because sometimes the first thing we try just doesn't work. You know, if you think about the way ECT works, a wider pulse-width probably is creating an electrical field that's penetrating deeper into the brain. If you just think it's starting with a, if the field diminishes, the deeper you go into the brain, if you start with kind of a wider pulse, you're probably reaching deeper structures. So there probably is some qualitative difference of using the brief pulse treatment versus ultra-brief, but still for the majority of our patients, ultra-brief is adequate. So that's why we always start with that, but we just don't limit ourselves to that one type of treatment. That makes sense to have these options. This is a question saying, you were talking about kind of to maintain gains, offering people MAOIs or lithium. What if someone says, if I'm not comfortable prescribing MAOIs or lithium to patients, are there other medications that you suggest or other antidepressants that are not MAOIs or would any antidepressant work? Really, any antidepressant works. You know, as you can see kind of from the studies, there actually haven't been a lot of studies of the use of SSRIs or other medications post-ECP. So, you know, honestly, we really recommend whatever a patient will tolerate and particularly if it's something they haven't tried before we'll recommend it. You know, one thing about, just to say about lithium, I know a lot of people are not as comfortable prescribing lithium, but often when we use lithium as an augmenting agent, we're not aiming for actual therapeutic levels the way you would if you were treating someone with bipolar disorder. So often you can kind of aim for much lower doses, which hopefully people might be more comfortable with just because the risk of developing lithium toxicity is a lot lower. So just something to at least consider adding into the mix. But yeah, so we will really recommend that patients try whatever they haven't tried before or, you know, whatever their prescriber feels comfortable with. One thing about MAOIs is we have tried people on the Selangeline patch, which, you know, you don't have to be as careful with the dietary restrictions. So that often is a good option as just a different class of medication that patients have not tried before. Got it. And this is a question, if someone reports that they got ECT a long time ago, they don't remember kind of how it was, what specifics were, and their interest in ECT, are there any kind of contraindications if people have had ECT and maybe not responded, not had a positive, the question is not got side effects, but not got much better from it. Would you consider retrying or re-challenging ECT? Yeah, we absolutely would. And actually it's interesting, I was talking with this guy, Harold Sackheim a few weeks ago at a conference. He was telling me about a study that he had done looking at patients who had not responded to ECT and then doing another trial, particularly with bilateral treatment. And I forget exactly what the number was, but the remission rates were very, very high with a re-challenge with ECT. So yes, even though patients didn't respond the first time, we definitely, if they still are having a depression characterized, particularly by a lot of neurovegetative symptoms, we definitely recommend that they get another try. That makes sense. And we have about one more minute for questions. Another one is, avoiding terms like anterograde and retrograde memory, which can be confusing to patients. How do you kind of explain to patients the memory side effects in a way that's relatable and understandable? Sure. So what I tell patients is that ECT will interfere with your ability to lay down new memories during the time that you're having treatment. So that patients will experience essentially gaps in their short-term memory for events taking place during the time that they're having their acute course. And I explained to them that they tend to be very minor things like they have a conversation with their wife and then the next day they forget the details of the conversation, or they're watching something on Netflix and halfway through they realize like, oh, wait a minute, I saw this episode a week ago. But that it really tends to be confined to those one-off unreinforced incidents. Those tend to get lost with ECT. But again, with ultra-brief pulse, they tend to be pretty minor. And then I also explained that they tend to have, patients tend to have a slowing of recall of things that they already know. So often they'll be in conversation, they'll have difficulty pulling out a word or remembering the name of their favorite actor who pops up on the TV. That's not something that patients typically notice. But again, it's really limited to the time that they're having their acute course and will really start improving as soon as the treatments get more spread out. And certainly once they're as spread out as every two weeks, their memories are getting very close to back to normal. But they will have these discrete gaps of memory from the time that they were getting their treatment. That makes sense. And one final question, we may have to respond a little quickly, but what are the relative contraindications for ECT? Sure, sure. So relative contraindications are heart rate and blood pressure does go up during treatment. So anyone who has significant cardiovascular or pulmonary disease, we have to proceed with caution, although it's not an absolute contraindication. Patients with seizure disorders, we will proceed with caution, but we can still treat patients with seizure disorders. Patients who have large masses in their head probably shouldn't get ECT just because of the transient increase in intracranial pressure. So there is a theoretical risk that you could have a brain herniation, even though if it's a stable mass, like a meningioma that someone's had for 10 years, it's probably safe. So the absolute contraindications are really rather few. Another one, just in the context of McLean Hospital, because we're not a medical hospital, if patients have bad GERD or reflux, we won't treat them in our hospital setting just because of the risk of aspiration during anesthesia. But again, that's not an absolute contraindication. So basically there aren't really absolute contraindications. They're just conditions in which you would exercise more caution. That's perfect. So I'm actually gonna switch us to the next slide, which so if we were able to get the most questions, do you have follow-up questions about this topic or any related to evidence-based care for SMI? Our clinical experts are available for online consultation. Any mental health clinician can submit a question and receive a response from one of our SMI experts. Consultations are always free and always confidential. We'll go next slide. SMI Advisor is just one of many SAMHSA initiatives designed to help clinicians implement evidence-based care. We encourage you to explore the resources available on mental health addictions and prevention, TTCs, as well as the National Center for Excellence for Eating Disorders and Suicide Prevention Resource Center. These initiatives cover a broad range of topics from school-based mental health to the opiate epidemic. And to claim credit for participating in today's event, you'll need to have met the requisite requirements for your profession. Verification of attendance can take up to about five minutes. Then you'll be able to select next to advance to complete the program evaluation before claiming your credit. And our final slide is, so please join us in three weeks on July 15th, 2021, as Dr. Robert Coates from Emory University presents Leveraging Knowledge of Clozapine, Pharmacodynamics and Pharmacokinetics to Improve Outcomes. Again, this free webinar will be on July 15th, 2021 from three to four. So I wanna again thank our speaker, Dr. Roseman, and thank you everyone for tuning in. Till next time. Thank you.

electroconvulsive therapy

ECT

mental illnesses

psychotic depression

catatonia

delirious mania

treatment-resistant schizophrenia

electrical stimulus

bilateral electrode placement

maintenance treatment