So, Ian, I want to jump right into the questions, because we've gotten some really great ones as we've gone through. So, one of the first questions that came in was around negative effects from TMS, and the individual is wondering, they understood what you explained, but for things like the tapping and the headache, does that resolve, and about how long does that take? So the tapping sensation is present only when the device is actually activated. So as soon as the session's over, no more tapping. A headache, if it happens, and it happens only in a minority of people, it tends to be present just for the first maybe two or three treatments, and then it's no longer an issue. If you look at the actual dropouts from the first trial, all reason people withdrawing from that study was about 5% of the subjects, which is in contrast to maybe 20, 30% of subjects who drop out of a drug trial because of side effects. So this is much better tolerated, in my opinion, and the data tends to support that. But as soon as the session is over, the tapping has gone away, and usually by session three, there's no more headache problem. Wonderful. Would TMS be appropriate for a person who's managed MDD for many years with medication, but who would prefer to leave medication? Boy, this is a question which I have gotten many times over the years. Okay. Usually, usually posed by a person who is on meds, is doing well, but is wary of the side effects or the burden or, for whatever reason, wants to get off their meds. Because TMS doesn't work for everyone, the way in which we usually assess, is it helping, is by following symptom changes. And many of us, most of us probably nowadays, do this with structured rating scales as well as with direct one-on-one interview with patients. And so in the absence of having symptoms to follow, it's hard to know, is this treatment working for this person or is it not? And they're just well because they're still well after ending their medication. So in general, what I have counseled patients over the years is, if you are doing well on your medications, you have to think about what is the likelihood of doing well with TMS. And it's pretty good, but not perfect. What are the consequences of having another depressive episode? And if a person rapidly becomes suicidal, if they become impaired and can't work or can't function at home or whatever, you're balancing potential risks and potential benefits in a way. What I usually make as sort of the bottom line for many patients is, thank you for coming in to meet with me. Now that we know you, now that we're all set, we can pull the trigger and start TMS whenever it makes sense. If you and your regular physician want to have a trial off med, we're here to help catch you if the symptoms, if and when the symptoms come back, and we'll be all set to go. And a practice where there's insurance clearance needs to be obtained ahead of time, that often takes many weeks, and so needs to be lined up ahead of time, of course, as well. And very often we have people where we have a good initial evaluation and hear from them several months later, and they said, okay, I decided to go off my meds. Or sometimes they say, I didn't decide to go off my meds and I had a relapse nonetheless, so let's try TMS now. But in general, most practitioners are not keen to treat with TMS if there are no symptoms to follow to give you an indication as to whether it's effective or not. Wonderful. So can you please say more about what we know about using TMS in treatment-resistant psychosis? Sure. We need a lot more data here. But what we do have pretty strong evidence for is that there can be benefits for things like drug-resistant auditory hallucinations. And here, rather than treating over the dorsolateral prefrontal cortex like we do for mood disorders or for anxiety conditions, the target is actually nearer to the ear. Heschl's gyrus is, I believe, the name of it. It's a well-described target back there in the temporal cortex. And sending in inhibitory pulses to help reduce the activity in that auditory network tends to reduce the auditory hallucinations. So, practitioners have told me things like, yeah, I still hear the voices from time to time, but they're not nearly as bothersome, and they're no longer, the content is not as disturbing as it had been before, you know, there are no mad hallucinations, things like that. As far as helping with other positive symptoms, that hasn't been demonstrated all that much just yet. And there is still a lot of work to be done with negative symptoms, but one would think that stimulating areas of the brain that are involved in decision-making, in emotional reactivity, might have a potential for being a benefit for the negative symptoms there, too. We just need more data. All right, I think this will be my last question, but it's a three-parter, so hold on here. So, it's all about seizures. So, what's the incidence of seizures during TMS sessions, that's one. Are the seizures generalized tonic-clonic type, that's part two. And if a patient has a seizure, does that preclude further treatment sessions? Okay, so in somewhat reverse order, there are people who have had a seizure with TMS, who then got worked up, and depending upon what was found, many of these people have gone on to go back to TMS, although, as you can imagine, with a certain amount of nail-biting by the treaters, and have successfully completed it without further seizure, and have done well in terms of being clinical responders. To the best of my knowledge, and here I have not had any direct experience with seizures happening, knock on wood, for over the past 11 years of doing this, some of the time it has not been a full generalized tonic-clonic seizure. Sometimes it has just been a partial seizure. And this depends a little bit on what is going on. So, for instance, of the reports of seizures with TMS, if the problem is that the magnet was not placed correctly, and was placed too near to the motor cortex for whatever reason, there you're going to actually be stimulating the motor cortex in a way that may lead to kindling and a seizure event. But then it's over. One seizure event was related to a patient, as the story goes, who was especially anxious one morning and took double his usual dose of bupropion that day. We all know that bupropion is associated with seizures in people who have electrolyte abnormalities. It does tend to affect cortical excitability. And so here it seems that taking that extra dose of medication and not sharing that information with the treatment team was part of what led to the seizure happening that day. My understanding is that if a person's on a medication that changes their cortical excitability, the general practice is, if there's a change in med, you re-measure how strong the magnetic field needs to be. It doesn't take that long to do and gives you and the patient that extra degree of safety. As to the actual numbers, my recollection of the most recent analysis of this suggests that it is less than 0.1 percent of treatment sessions have had a seizure event associated with them. Again, it's on the order of a few dozen seizures over worldwide use of this over the past decade. So it is a very rare event.

Transcranial Magnetic Stimulation

TMS therapy

negative effects

medication-resistant depression

seizures