Ep. 163- Interview with Dr. Geoffrey Grammer: New Frontiers in Treating Depression When Meds Fail

What if you've tried everything, but are still depressed? Did you know that  one third of people with depression don’t get enough relief from antidepressants? In this episode, I talk to psychiatrist and CMO of Neuronetics, Dr. Geoffrey Grammer, about what should people do when our mainstream treatments for depression fails us. He sheds light on new advancements for treatment-resistant depression: transcranial magnetic stimulation (TMS) and nasal esketamine, two evidence-based treatments that target the brain differently and raise the odds after meds stall.

We first talk about just how disappointing traditional medications and psychotherapies can be for chronically depressed patients. Then, Dr. Grammer explains how TMS works (precise, noninvasive brain stimulation that strengthens underactive mood circuits), what a session feels like, timelines for improvement, and why side effects are minimal compared to systemic drugs. We also explore nasal esketamine (Spravato) and how it works. Along the way, we dig into augmentation meds, common pitfalls, and the role of psychotherapy in turning short-term gains into lasting change.

Real patient stories ground the science in hope: remission after years of struggle, renewed presence with family, and the hard-won confidence that life can feel different. If you’ve tried two antidepressants without clear progress or hate the side effects, your next step shouldn’t be “another pill” - it should be to advocate for yourself with your providers and explore these new options.

Resources:

• NeuroStar website: https://neurostar.com/

• NeuroStar's assessment quiz for depression: https://neurostar.com/self-assessment-for-depression/

• Find a doctor page: https://neurostar.com/enter-zip-code/?as=0

• Connect to Dr. Grammer on social:

  • https://www.instagram.com/NeuroStarAdvancedTMS/

  • https://www.facebook.com/NeuroStarAdvancedTMS/

  • https://www.youtube.com/user/NeuroStarTMSTherapy

• Transcript

  Dr. Kibby McMahon: 0:00

  Hi guys, welcome to A Little Help for Our Friends, a podcast for people with loved ones struggling with mental health. Hey little helpers, it's Dr. Kibbi here. Before we dive into this episode, I wanted to tell you how I could help you navigate the mental health or addiction struggles of the people you love. Coolamine is the online coaching platform and community that I built to support you in the moment when you need it the most, like having hard conversations, asserting your needs, or setting boundaries. Even if you're just curious and want to chat about it, book a free call with me by going to the link in the show notes or going to coolamine.com, K-U-L-A-M-I-N-D.com and click get started. Thank you and enjoy the show. Welcome back, little helpers. We have a really cool guest today. His name is Dr. Jeffrey Grammer, MD, is a psychiatrist and a pioneering trailblazer in mental health care.

  Dr. Geoffrey Grammer: 0:49

  So I think it's important that your listeners understand that what we now know is that one-third of patients will not get adequate relief from medications alone, no matter how many medications you try, no matter what the combination is. And it is not their fault. They're not broken, they're not doing something wrong. This is the limits of medications. And for 70 years, medications worked on one of three neurotransmitters within the brain: serotonin, dopamine, and norepinephrine. But if your depression isn't tied to one of those three neurotransmitters, it's not going to respond to the therapy. So for decades, we had these non-responders, not because they were wrong or broken, but because the therapies were limited in what they could treat. So what's really nice now is that, you know, after two medications, the likelihood of responding to a third or fourth starts to go down precipitously. But now we have new therapies and modalities that work substantially better in that population of folks, and more stuff is coming down the pipeline soon.

  Dr. Kibby McMahon: 2:00

  Whoa, okay. I didn't know that it was as high as one-third of patients don't respond to antidepressants. Can you say why do we do you know what depression doesn't actually respond to antidepressants? I don't actually know this.

  Dr. Geoffrey Grammer: 2:15

  Yeah, we actually don't quite have the capability yet in psychiatry to be able to diagnose why someone is depressed. We have some markers to suggest that. But the metaphor I would use is think about antibiotics. You know, for years we had these antidepressants that work very specifically on those neurotransmitters. It would be like only having penicillin. But if you have an infection that is resistant to penicillin, it's not going to get better. Right? And this isn't my opinion. There was a large trial that was done called the STARD trial, which replicated real-world antidepressant treatment. And that was actually sponsored by the NIH. And they showed that if you follow this very specific algorithm of escalating care with meds, you still leave one third, you know, behind. And I think it's because depression is a heterogeneous disease, meaning it has multiple causes. Think of it like headache. You can have headache for a lot of reasons. Sometimes Tylenol works, sometimes Motrin works, but sometimes you have to take like sumatryptin, right? So depression is probably the same way where it has multiple causes. And though we don't have the ability yet to say, here's why you have depression, therefore here's the modality. What we do have is, hey, we tried this, it didn't work. Now let's try this.

  Dr. Kibby McMahon: 3:32

  That's so no idea. What is what does treatment-resistant depression look like? Like, I mean, there's a ton of people who were who go, well, I'm gonna consider SSRIs, but I'm scared, I'm scared of getting antidepressants. What if it doesn't work for me? What how what does it look like when someone is treatment a treatment resistant?

  Dr. Geoffrey Grammer: 3:54

  Right. So by definition, treatment-resistant depression is a a um lack of response to at least two antidepressant trials. Now, to put this in perspective, the patients that I see in my practice have been on an average of eight medications. So they blow through that definition. And I think it's important to recognize like what that does to somebody, right? Because, you know, a lot of them drop out of care altogether. They're like, I'm not going to go see a psychiatrist anymore because they keep putting me on stuff and I get all the side effects and none of the benefit, and this isn't helping me. I see a lot of people internalize, you know, shame inappropriately, where they they assume like it's I'm doing something wrong, I'm not thinking about the world right, I'm not exercising enough, I'm not sleeping well enough. And that's not it, right? And so, you know, unfortunately for a lot of people, and I think we haven't done a good job in psychiatry at really educating people on this, but they personalize that lack of response. And that causes them to fall out of care and to further, you know, lean into this idea of self-responsibility for their lack of response. And that's not the case, right? So part of our goal is not only to have people currently in psychiatric care come see us for things like neurostar TMS therapy, but we actually need to reach out to those who are in the community that aren't in care at all and let them know that something fundamentally different is finally out there.

  Dr. Kibby McMahon: 5:14

  So interesting. What about ECT or any of those, you know, before we get into the cool interventions, like what about, you know, psychotherapy? What about um ECT? I mean, I think I think the question that pops up in my mind is there's some people who have so who have such chronic depression that they don't know what gut getting better looks like. You know, they might feel a little bit better, you know, or they just might have that more negative outlook. Like what does what what does what should they expect from from a treatment? And what about those other ones that we have?

  Dr. Geoffrey Grammer: 5:51

  Like, yeah, so for years ECT was the sort of next step after not responding to medications and therapy. And a lot of people had concerns about that. Some of it was stigma associated with the idea of ECT. The way we did it way, way back in the day led to a lot of memory problems. You know, we're it's a it's a lot better technology now, but it still is labor-intensive, and about 70% of patients will develop temporary memory issues with that. So it's it's not an appealing uh option for some people, particularly if they're currently working, if they have childcare duties, if they can't take time off. You know, that just isn't an option. For some people, it's life-saving, no doubt about it. And it should still be out there as an option for folks. But what about, you know, the kind of walking wounded is what we used to call this in the military. Those who are going to work or going to school, they're kind of doing their stuff, but they're still suffering. It's not reached the level where it's life-threatening, but it is impacting their overall sense of well-being. And so something less invasive than ECT was definitely needed. You know, Neurostar TMS was one of those things that filled in that gap. So, um, and I I forgot the second part to your question, but one was the ECT part, and the second part was I think I I think it was just kind of like I was thinking about what um what people can expect from treatment.

  Dr. Kibby McMahon: 7:09

  I think that's the thing because like some people will take antidepressants or they'll get therapy, and uh some some things might improve and some some aren't. And and sometimes it's our job as psychologists to try to explain what getting better looks like. But I think when we're talking about like treatment-resistant depression or effective treatment, what does that look like with someone with like chronic serious depression?

  Dr. Geoffrey Grammer: 7:34

  Yeah, you know, it's interesting because and there's two parts of this, you know, one is therapy and where does it fit within this? And the other is, you know, what can people expect? And to your point, we certainly have seen this where someone has been depressed for so long that when they start to feel better, it can feel foreign. And and it can lead to issues of who am I now that I'm not depressed? You know, on a very practical level, if every weekend you spend it in bed sort of staring at the ceiling and all of a sudden you're feeling better and you're like, well, what do I do? And and you don't have the repertoire of sort of options that you've just practiced for years and years, and suddenly you have to create that. The, you know, I often tell people the one of the best times to do therapy is when you're feeling better. Because even though these meds can help with you know some of the physical symptoms of depression, sleep, and so forth, sometimes patterns of thinking and behavior can persist after the depressive episode has resolved. And that's where therapy can be absolutely critical, right? And so I would encourage people that, you know, if you're going through this and you're starting to feel better and you're like, man, I don't feel the way I'm used to feeling for the last eight, 10, 12 years, you know, that's very normal, but you're going to establish a new normal that feels a whole lot better and it's going to allow you to be a lot more functional and during that time to ease into that new kind of mindset. I highly encourage my patients to engage in therapy if they're not already.

  Dr. Kibby McMahon: 8:58

  Yeah, that's really beautifully said and beautifully describes why we say that medication plus psychotherapy or any other kind of behavioral intervention is good because they're like, oh, I'm just taking the, I'm just I'm on the meds now. Isn't that enough? And you know, I've always thought about it as like the meds can be like gas on a pedal, but it's like psychotherapy helps you know where to drive. So it's like you might have the energy, you might have more flexibility and engagement, but it's like what you do with that then, like where are you gonna put your attention? Where are you gonna put your thoughts and energy and things like that? So I really like the way you described it.

  Dr. Geoffrey Grammer: 9:39

  Yeah, absolutely. I you know, we always think in medicine everything at risk and benefit, right? And and the risks of therapy are exceedingly small, right? Yeah. But the potential benefit is huge. And so it's one of those things where, you know, I I think patients should really try to embrace and find a good therapist. I I would put one thing out there. I tell people, you know, finding a therapist is a little bit like a blind date. Like sometimes it's not a good match and it's no one's fault, right? It just you you meet with someone and you're like, we're not gelling. I don't feel like this person gets me. Don't turn off the idea of therapy just because you didn't meet with a therapist that you felt you resonated with. Meet with another. And and a good therapist isn't going to be offended by that. You know, I I think we as providers, you know, I have people that see me where I'm like, hey, do you are you do you feel like we can work together? And if they say no, Michael, let's get you someone who can. Like that it's not personal for us. We get it. It's your journey, it's your life. You need to have the people on your team that you want.

  Dr. Kibby McMahon: 10:39

  Yeah, that's a good point. Should should we do the same for medications? If you're if the after two is considered treatment depression, uh treatment resistant, and I've like tried one, and then I've tried someone tried Prozac and then Lexapro, and then they're like, oh, now they're feel great. At what point sh should they go, uh-oh, this is this is a medication problem? And I gotta do something else.

  Dr. Geoffrey Grammer: 11:05

  There was a study done that took people who had not responded to two medications, and they were randomized to receive either a third or to get TMS therapy. And the group that did TMS therapy was significantly more likely to achieve either a remission, meaning asymptomatic, or a response, meaning a 50% decrease in symptoms, than the third medication group. So if you're playing the odds, you are more likely to respond to TMS therapy than you are a third medication trial. There's also a similar study looking at what we call augments, like probably the most common out there is aeroprazol, right? Otherwise known as abilify. Same thing. If you're randomized to either, and you know, again, this was a smaller study, but it was significant. If you're randomized to receive either TMS or aeropiprazole, you're more likely to respond to TMS. And it gets back to that idea that for some patients, medications just aren't the treatment that's going to be effective for you. It's the medications that are failing the patient, not the other way around.

  Dr. Kibby McMahon: 12:09

  Can you tell me a little bit more about what those medications do, like abilify? I've always looked at those commercials and I'm like, you know, if your antidepressant medication isn't working, put another one on. And I'm like, oh, like, how does how does that work?

  Dr. Geoffrey Grammer: 12:22

  Is it is it does it work? Yeah, I mean, treatment-resistant depression is really fascinating. And what happens out in the community is a little bit different than what the evidence shows. And and that's not because doctors are doing stuff wrong. Like we're trying to help people. And, you know, research studies are always so narrow because you have to control the number of variables that it never extrapolates real easily to the real world community, right? But with that being said, let's go over kind of what that journey is like. Most people will start an antidepressant, usually one of the SSRIs, because they're they're you know easy to take, they're low cost, and they have a favorable safety profile. Um, and if that doesn't lead to an uh an adequate response, then they'll often go to a different antidepressant in another class. So the SSRIs work by inhibiting the recycling of serotonin within nerves, so it increases serotonin used to transmit between two nerves to talk. Some of the other classes are like SNRI, serotonin and norepinephrine reuptake inhibitors, or like buproprion is a dopamine orpinephrine reuptake inhibitor. So they work on some other neurotransmitters, but most of them have the same effect of increasing neurotransmitter response. Now, there's a some of the newer agents do some fancy stuff, what we call postsynaptically, on the receiving nerve, where it can try to fine-tune which receptors get stimulated and which don't. But no antidepressant on the market has consistently shown superiority over another. They all work about the same. So don't let any provider say, well, I like this because it works better. That literature doesn't exist, right? Like that's just not out there. In addition, there's no consistent convincing evidence that two antidepressants at once are better than one alone. There's a couple of studies that hint at it, but it is hardly compelling. And we see a lot of people come on on two antidepressants, and I do that sometimes too. Like it's just part of what we do, but the evidence isn't really there. So then the idea came up with these augment strategies. And the medications that were originally developed for bipolar and schizophrenia at low dose were found in clinical trials to be significantly effective for people who aren't getting enough response from just an antidepressant alone. We're not entirely sure how they work. There's different theories. Part of it is it may increase sort of dopamine activity within the brain. Dopamine is sort of that pleasure reward response neurotransmitter. Um, there's some fancier mechanisms that that it probably aren't worth going into, but you know, helping receptors do fancy things on the receiving nerve. But they were shown to be effective, but they have serious side effects. They can increase weight gain, they can cause uh sexual dysfunction, um, and they can cause a sense of restlessness or what we call extrapyramidal symptoms, otherwise known as like Parkinson-like symptoms. And so that limits some of their utility for folks, and it causes concerns with long-term safety.

  Dr. Kibby McMahon: 15:12

  That's so interesting. Um I just have so many questions. I feel like I'm getting like selfishly like a whole you know overview of psychiatry because it's it's it's something that we always work with as psychologists, but don't know the the details about it. I have heard I have heard that some medications, like well butrin, some people are like, this is it saved my life, this is amazing. And some people have had a really um, I'm I'm I'm talking about this anecdotally. I've I've seen some people and some patients who uh it's it's an astoundingly bad, you know, not even just like it doesn't work, it doesn't treat more of their depression, but they get worse. They some people were aggressive or um uh even thought of self-harm are more impulsive than they were before. What like what has have you have you seen that before? Do you know anything about specifically well butrin are a different class of medications?

  Dr. Geoffrey Grammer: 16:09

  Yeah, that's that's part of the reason why antidepressants require someone who's licensed to prescribe them be the that portal of entry, right? Because any treatment we do in medicine can have side effects and risks, right? And what I will often tell patients is any medication can have any side effect in anyone. But let's take well butrin, otherwise known as bupropion, for example. Well butyrin looks molecularly somewhat similar to a stimulant, and it inhibits the re-uptake of dopamine and norepinephrine, which are two activating neurotransmitters. People with a propensity towards anxiety or a history of trauma may get a worsening of symptoms if you're on well butrin. One of the side effects of well butrin is anxiety. Another side effect of well butrin is those who are prone to have, say, perceptual disorders, um, what we would call hallucinations. Actually, hallucinations can be one of the side effects of well butrin. It's rare. Most people do great, but some don't. So whenever I start a patient on a medication, I tell them, like, you know, here's the things to watch out for that are common, but any medit can have any side effect in anyone. And if it makes you sick, stop it and call me. You know, we will often ask people to kind of tolerate a few days of nausea or maybe a little fatigue or headache. Usually that kind of stuff gets better. But man, if you take it and you start throwing up all over the place, like talk to your provider. Like, like I wouldn't ask someone to be on a medication that does that. Same thing with weight gain. Like, that's another good example of, you know, I I don't think it's necessarily fair to tell a patient, I'm going to put you on this Lexapro, and they gain 40 pounds, and you're like, wow, tough luck. That's not okay, especially when we have other treatment options. So sometimes it's a little bit of trial and error. We try to make educated guesses on what medicine might work best for someone based upon some of the mechanisms I've talked about here, but we don't always get that right. Everyone's physiology is unique and different. And so I think the biggest thing is, you know, you need to feel like you can have a conversation with whomever is prescribing that for you. And if you have concerns about adverse effects, make sure you talk to them about it. And they'll either tell you, like, hey, this happened sometimes, you can get through it, but other times you're like, no, this is the wrong medicine for you. Let's try something different. You're not taking the meds to make your provider feel better. You are paying your provider to give you advice on how to feel better. And if that isn't happening, you know, they should be giving you different answers.

  Dr. Kibby McMahon: 18:36

  That's such an important message for people to hear because I think a lot of people do get prescribed their um psychiatric meds from general practitioners or just people who go, okay, you're depressed. You know, try try Lexapro out. Let me know how it goes. And, you know, some people might say, okay, I'm feeling better, but you know, I'm struggling with waking. But uh, you know. So I I I I love the message of talking to your provider with any concerns and not just blaming yourself, so which with depression tend to do.

  Dr. Geoffrey Grammer: 19:08

  So yeah, I'll I'll tell you an anecdotal story, which which, you know, when I was a uh junior attending, right? And and unfortunately I'm I'm coming up on my 30-year medical school reunion. Like, how crazy is that, right? Congrats. Anyway, way back in the day, I remember I was seeing somebody who who said, Hey, you know, I started him on fluoxetine or Prozac. Make him saw me, he's like, I'm doing okay, but I'm sweating on half the side of my face. And I thought, this can't be a side effect, right? So I do a literature search and find that indeed that has been reported with Prozac. And what it taught me was no one is a textbook, no one is a clinical trial, everyone's an individual. Listen to your patients. If they say a medication is causing a side effect, it's causing a side effect. Take it seriously, right? So, you know, just because you can't read it in the package insert doesn't mean it's not happening to you. If you're experiencing it, you should feel very open and comfortable talking to your provider about that. That's good. That's good to what half of the face? Uh well, it can be either half. It's just it's it activates, you know, there's we actually doubt yeah, oh yeah, it's like midline over Yeah.

  Dr. Kibby McMahon: 20:23

  That's wild. It is a wild side effect. All right. Let's say it's not working, medications isn't working. I don't know if I could ever get better. What are the new frontiers? Tell tell me about TMS and like what what is it for people who don't know what that is.

  Dr. Geoffrey Grammer: 20:43

  Yeah, so TMS or transcranial magnetic stimulation therapy, okay. Is a um, it was actually FDA cleared back in 2008 for major depressive disorder, actually treatment-resistant depression. Um, and and it has since gotten actually FDA clearance for adolescent depression down to the age of 15, as well as obsessive-compulsive disorder. And what we do is we take a powerful magnet, not like a refrigerator magnet, but like an MRI-ish magnet, uh, much smaller though, and we place it on the scalp and it pulses a magnetic field down onto uh the brain. And when it does that, it will gently stimulate the nerves in that area of the brain and exercise them, depending on the frequency we use, but usually it will exercise them. And um and what we know in depression is that there's an area of the brain that is often underactive. So instead of taking a medication, for example, that systemically goes throughout your body and is everywhere and bathes your whole brain in this stuff, with TMS, we can go in and directly start to activate an area of the brain that we know to be underactive in some patients with depression. And when we do that every day, just like going to the gym, that area gets stronger and it starts to pick up the activity on its own. And as it gets stronger, we see improvement in the depressive symptoms. So, you know, it's it's I I think the best medical metaphor for this is it is physical therapy for the brain. And it's not pseudoscience. You know, neurostar TMS therapy actually was studied in a uh sham-controlled trial where half the patients got fake treatment and the other half got real treatment, and they didn't know what they were receiving, so they were blinded to that, right? So it's it's a good evidence trial, and it showed significant benefit. And there's been numerous trials since then confirming that benefit. And the FDA reviewed it and approved it. And what's nice about it is because it doesn't have those systemic side effects, you don't get sweating on half the side of your face or weight gain or sexual dysfunction or any of the issues that you have with medications. And what we have seen, you know, the data that Neurostar has for adults is up to 83% of patients who didn't get better with medication therapy will have a significant improvement with Neurostar TMS therapy. And that is huge. Adolescents, it's 78% can have a significant improvement in symptoms. So when I say it's a paradigm changer, I mean it's a paradigm changer.

  Dr. Kibby McMahon: 23:27

  No, I mean I I've the only the only exposure I've had to TMS is my colleague at Duke is is running trials of TMS for emotion regulation and and trying to stimulate the areas that are um responsible for regulatory, you know, changing the way they're thinking about their emotion. But I didn't realize it's this effective as a as a standalone treatment for depression. It this is I wish I I wish I'd you know caught up on my uh neuroscience knowledge, but is it the same for everyone across different kinds of depression or different individuals? Is it usually the same brain areas that are underactive, or is it you know person specific where you'd you know have to put that magnet?

  Dr. Geoffrey Grammer: 24:13

  It's a good question. So um what I would say is there's no neurologic or psychiatric condition that you can think of that hasn't been studied with TMS at this point, right? So you'll find all kinds of stuff out there. But let's talk about what the FDA is kind of signed off on. So for depression, there's one sequence uh with the Neurostar TMS device that we use for treating depression that was cleared by the FDA, and that's treating over what we call the left dorsolateral prefrontal cortex. And for those on YouTube, if you're seeing my my face, that's like here, okay, which is my left side. I'm not sure if the camera's gonna reverse or not, right? Like right around here. But how we personalize it is tailored to the patient. So it's kind of cool because you think, well, how do you know where to go? Well, your your body is mapped out over the motor cortex in a very predictable fashion. It's called the homunculus, right? And there's an area that controls like your leg, your hip, your arm, and where's my camera? Your thumb. And what we do is we take the magnet and we put it in near the area of the motor cortex and we start hunting around until we can make the thumb twitch. And that tells us where we are in the brain. And then we adjust the energy level to the minimum amount of energy needed to make the thumb twitch by directly stimulating those motor neurons within the brain. That tells us the intensity to give, and then we move forward five and a half centimeters from that location, and that is the area that corresponds to the dorsal lateral prefrontal cortex. So it's mapped to the individual, but the ultimate treatment sequence is standardized to that evidence-based uh strategy that was done in the original clinical trials.

  Dr. Kibby McMahon: 25:57

  That is so fascinating. That is so okay. What's what's the catch? I mean, that just sounds too good to be true. You just, you know, you find it, you put the magnet, and then I mean, what does a treatment look like? Like how long does it take? Are the things that are going to be?

  Dr. Geoffrey Grammer: 26:11

  Yeah, so people will sit back in a in essentially a uh it looks like a dental chair. Right. And um and they lean back and you know, we place the coil on the cap. And it and the the magnet is in sort of a thing that looks like almost like a small kid's shoebox. It's about that size. Um it's five, for those that care, it's 10 centimeters across and about, I think, 15 lengthwise. Um and you know, the the provider will actually map out that location and then and then put it into treatment. And then most places will have a technician that administer the daily treatments. The treatments last depending on the sequence, but the current FDA sequence that we recommend is um 18 minutes and 45 seconds. There's another FDA sequence that's a lot shorter, but I I think um most providers do that 18 minute and 45 second sequence. It might need to be customized. So it's if it's not that, don't come back and do like hate in the comments. Like it's there's a little bit of customization. And while you're getting treated, you're totally conscious, totally awake. You can surf your phone, you can watch TV, you can talk to somebody, like you're you're not out of it at all. And then when you're done, the the chair, you know, take the coil off the head, the chair comes up, and you go out and you can hop in your car and drive and go to work and go to school, and you are there's no downtime. Right? So it's it's literally physical therapy for the brain, right? Um, you know, during the treatment, your scalp nerves are on the way to the brain, so they get stimulated too, and it can feel like tapping on the head. Um, but for 95% of patients, that tapping is well within tolerable limits. And usually after about three days, most people get used to it. I'll tell you, some patients will even take a nap in the middle of it, they just kind of fall asleep because the chair is pretty comfortable. But it's it's actually for what it sounds like, it is a remarkably sort of easy and safe treatment for people with depression. And and you say, what's the catch? You know, even if you look at the most conservative efficacy data, I'm gonna put a pin in it and say that the probably the lower end is like 50%, and and the average data is about two-thirds of patients get better, right? Um, with with the partic specific scales that I cited before being up to as much as 83%. All of that is tremendously huge for people that have not responded to multiple medications in the past. But the number one barrier is awareness. And that's what's so maddening, right? Depending on which data you look at, like right now, today in the United States, there's millions of people, up to, depending on the statue look at, 4.7 million people with treatment-resistant depression. And an infantesimally small number of those have ever even been offered neurostar TMS therapy. And that's one of the biggest tragedies of this. So, my recommendation to your listeners is you know, like if you have been down that medication wheel and and you want to try something different, like find a neurostar provider in your area. If you go to neurostar.com, there's a little physician finder, you type in your zip code, it'll show you the providers in the area, and go meet with them and see if you're a candidate. Like the worst case scenario is let's say you're not for whatever reason, but man, it can be life-altering for you. And that and the evidence shows that you're more likely to get better with that than the umpteenth medication trial.

  Dr. Kibby McMahon: 29:21

  Wow. I mean, this, you know, case in point, I didn't realize that this was just available that people can just go and and get. I thought it was still being trialed or it's still in very specialized clinics, but you neuroscience is that just one company? Does do several companies make it? Like, can you just go to a clinic? Or, you know, where are where can someone find TMS?

  Dr. Geoffrey Grammer: 29:44

  Yeah, I mean, there are multiple manufacturers, right? So so I work for Neurostore. Obviously, I think our device is better, and I can certainly talk about why that is. Um, but there are other manufacturers out there for sure. You know, quite I mean, honestly, sometimes if I have someone that's moving to an area where There's not a Neurostar provider, I'll open up Google Maps and I'll say TMS near me and uh and it'll show all the providers in the area. You know, and and there are different providers out there. What I will tell you is, you know, at Greenbrook Wellness Centers, um, we take, I'll I'll use the the air quotes most insurance, which is my way of saying like nearly all. Uh, I'm sure there's like some small insurance company out there, but we will do all the lifting for you to try to, you know, get your insurance to approve this so that your out-of-pocket expenses are as low as possible. And we're very good at that, right? Usually most insurance at this point requires that you try one or two medications and you have a course of psychotherapy. And if those things are completed, you may be a candidate. There are a few contraindications, right? Um, if you have, you know, essentially metal above the neckline, and by metal I mean medical metal, not like dental work, jewelry, and stuff like that. But if you have like a ventricular peritoneal shunt or a cochlear implant, that could be a contraindication, right? There's a couple medical things like that that a good TMS provider will go over with you. But the vast majority of people, it's like, yeah, I've been on more than two. I've been on eight, 10, 12, and I've been seeing a therapist for years and years and years, and you're like, hey, let's let's do this. Worst case scenario is it doesn't work, and then we move on to something else. And there are other things that we can do too.

  Dr. Kibby McMahon: 31:18

  People, the patients don't have you ever gotten it before? Have you ever gotten it?

  Dr. Geoffrey Grammer: 31:22

  Well, I've never been treated, but what I will tell you is um every time we have a new provider or a new technician come on board, someone has to volunteer to sit in the chair and get tapped a little bit. So I have been tapped as sort of the volunteer while someone else is training.

  Dr. Kibby McMahon: 31:35

  And it actually works, or is it just like a placebo? No, no, it it's with the real taps. Do you notice any difference in the way you're thinking or you know, like uh functioning?

  Dr. Geoffrey Grammer: 31:45

  In physical therapy or going to the gym, it takes a little bit of time to start to kick in. We usually tell people give it about two to three weeks to start to notice a benefit. So a single treatment won't do that much. Um, there are some clinical trials showing some patients will score better within that first week, but it's kind of funny. Um, and you've probably seen this in your own practice, when people start to get better, they're usually the last to know. They'll score better on the rating scales, their family and friends will notice, and then they start feeling better. So you can score a little bit better within the first week, but most patients will start to feel better around the third week. Um, but during the treatment, yeah, it feels like someone's tapping you on the head. It it's in some ways underwhelming, but it it is a little bit of an odd sensation because uh it, you know, the magnetic field is just activating those sensory nerves in a way that normally they don't get activated, but um it's hardly um unpleasant, you know, and and again, most people tolerate it just fine.

  Dr. Kibby McMahon: 32:42

  Seems it still seems too good to be true. What can can people use it to enhance other areas of the brain without the depression? You know what I mean? Like, can I just be better at math? Can I get what about my memory? Can it can improve my get get me back to pre-baby's memory stage?

  Dr. Geoffrey Grammer: 32:58

  Well, you know, it's funny. I as as a uh representative of neuronetics, I have to stick with the on-label stuff. Um, but but I'm not kidding when I say like like this idea of it's a broader field of called neuromodulation. And, you know, I I think it's safe to say that there's a lot of interest in using this as a treatment for a variety of neurologic and psychiatric conditions. You know, we've got the the the sort of two things right now, actually to be more specific, there's major depress or treatment-resistant depression, um, anxiety with depression, actually received FDA clearance, the adolescent depression, and obsessive-compulsive disorder. And the way that we treat OCD is a little bit different than what we do with depression. It's a different location, and we do an exposure beforehand. Um, and it it accelerates the sort of um uh response prevention that happens with with the typical what we call ERP exposure response prevention. Um, do I think those are the last indications to ever uh come forward in the technology? No. Um, but uh you know, if folks are interested, you look online, you'll you'll find a lot of neat stuff out there. What I would caution some folks though, um I I'm a firm believer in doing evidence-based care, right? I I follow the literature closely. I I don't want to experiment on patients per se, right? Um make sure that if you see a provider that's promising you the moon, um, that you just confirm that what they're giving you is stuff that the FDA has said, like, yeah, this is a good thing. Because you you can find some providers out there that will claim to be able to treat all kinds of conditions. And I I think that's enthusiasm and altruism misplaced.

  Dr. Kibby McMahon: 34:38

  So what you're saying is I should find a sketchy, independent provider to bring back my my memory skills. Okay, great. That's great. Tell me, tell me why, um, tell me why your TMS is different than I mean, we're at the point where we didn't even know that we could go and find TMS, but why why do you why do you like your company better than the other manufacturers out there?

  Dr. Geoffrey Grammer: 35:00

  And I've used, I mean, you know, before I worked for Neuronetics, particularly when I was in the military, um, I've used a bunch, bunch of different devices by different manufacturers. And, you know, I I will say, I mean, they're all those that are FDA cleared are all safe and they can be effective. But Neuronetics, uh, who is the parent company for Neurostar TMS therapy, um actually is one of the only companies that did a placebo or sham-controlled trial to prove efficacy. The other manufacturers, with the exception of one, uh all said, well, we're like Neurostar as well, but they never did the study. Right? And that's one of the tricky things in devices is you can show equivalency through calculations and some measurement of your magnetic fields. Um, but they're not equivalent, and that's the problem. Because with Neurostar, we have what's called an iron core design. So the way the coil looks is it's a figure eight copper wrapping, but only our device has an iron core in the center to focus the magnetic field. So you get the stimulation in the area that you want, but not in the areas you don't want. And no one else has that technology. In addition, we have what is called contact sensing. And we have two sensors on the coil and they're very, very specialized so that if there's any issues with um roll or pitch of the coil, where you would end up sending the magnetic field to a different area because you're not directly vectored down over the area you want to stimulate, this will tell you if you're off center. It makes it sure it's perfect. No one else has that technology, right? We also are the only company that has what's called a magnetic gantry arm. So uh, like one of the devices I used to use had this like 20-pound coil that you you twist a little knob and suddenly 20 pounds falls into your hand, and you have to place it on the head and then twist the knob to tighten it up. Um, our gantry arm, there's a little button you press, and it's this nice fluid, almost ballet-like thing where you can place it on the head, you let go of it, and the magnetic locks fix, and it's just a lot easier to use. We also have proprietary software that allows us to track how patients are doing, allows providers to prescribe the treatment, you can follow their scores over time, um, and all that's cloud-based. So, you know, we were the first to market, and we have proprietary technology to make sure that providers are doing it exactly the same way every time that no one else has. So that's why I think we're we're better than others. But to be clear, if your choice is no TMS or a non-neurostar TMS therapy, you're better getting some TMS. But I would if I were to get TMS therapy, I would get Neurostar TMS therapy. I mean, that's and that's just being honest. I I think it's the better device. Otherwise, I wouldn't work here. I could go work for someone else.

  Dr. Kibby McMahon: 37:54

  That's good to know. I mean I mean uh we'll definitely link we'll definitely link your um your website and you know like a directory in the show notes just so people can can find can find your um TMS devices. Um now I'm realizing that I was just in San Diego in a behavioral health tech conference, and there was a booth, like an exhibitor booth, with a like TMS, and there was a person sitting there and in the middle of the exhibitor hall and getting TMS. And I was like, is this for real? Is this actually being like, what are they doing? This seems like a carnival trick, but I guess I guess it's so available that this legitimate that people are are getting can get TMS.

  Dr. Geoffrey Grammer: 38:39

  Yeah, I think, you know, if you think about it, psychiatry and psychology are are one of the areas of medicine that are so embedded in our culture. You know, it like there are some shows like ER and stuff like that, but there are very few shows where it's like, you know, in the weeds of a cardiology practice. But even the Sopranos, you know, have the lead actor going to therapy. So, so people know about this idea of mental health care, not just from engaging with that system, but because it's in all the stuff that we see with movies and TV and culture and dialogue and so forth. But that system moves a lot more slowly than medical innovation. And I think a lot of people are still cons conceptualizing mental health care based on the paradigms of care that are now 15 years old. And, you know, again, if if you if you don't want to believe anything I've said so far, please believe that there are options for people with treatment-resistant depression that don't involve just more of the same medications. And I prescribe medications and I think they're great and they're life-saving for a lot of people, but in the in those in whom it doesn't work, we now have actual evidence-based, FDA cleared, covered by insurance, treatment options.

  Dr. Kibby McMahon: 40:00

  Really cool. Really cool. Tell me a little bit about do you also do nasal ketamine or nasal ketamine ketamine?

  Dr. Geoffrey Grammer: 40:08

  Otherwise known as spravado. So we offer that as well, and that is another great option. About equal efficacy to TMS therapy. What that is, there's so a lot of people are familiar with ketamine for all kinds of reasons. Um, nasal S ketamine is sort of all that you want in the ketamine molecule and not what you don't want. It's a it's a very customized molecule by Johnson Johnson. And patients come into an authorized center, it's it's administered under an FDA program called the Risk Evaluation Mitigation Strategy or REMS to make sure everyone is safe. You get a very specific dose. There's only two doses, both are extraordinarily safe. Um we hand you the nasal spray device, you squirt it into your nose. We do that either two or three times depending on your dose. It will cause some mild intoxication. We have to monitor you for two hours to let that kind of pass and check your blood pressure and stuff like that. And then afterwards, you have to get a ride home. We typically will do it twice a week for four weeks, once a week for four weeks, and then once every one to two weeks thereafter. But that works very differently than medications do, at least traditional antidepressants. It it binds to a receptor in the brain called the NMDA receptor. And the reason that sounds new is because it is new, right? And it was shown in numerous clinical trials to be not only safe and effective in the short term, but actually the uh Johnson Johnson has maintenance data going out to now six years showing ongoing safety. And for listeners that maybe got spooked by the Matthew Perry tragedy, this is not that. There's a big difference between getting street ketamine and injecting yourself in the rear end and going to a hot tub and getting a medically supervised treatment at a dose that is effective for depression. Ketamine is one of those medications where it's interesting. We have a few things in psychiatry where more is definitely not better. And ketamine-based therapy is one of those, where higher doses actually don't work for depression. You have to get this dose that's very, very specific. And with nasal-less ketamine, that dose has been confirmed.

  Dr. Kibby McMahon: 42:13

  That's fascinating because I've always wanted to learn more. I've heard more and more people going to, you know, having very severe major depressive disorder, going to get um to a clinic and getting more um the IV kind of uh ketamine, and then doing great. And I was like, I was skeptical. I was like, uh, you know, curmudgeon, like, oh, it's just too good to be true. No, but it's really it's really an effective treatment.

  Dr. Geoffrey Grammer: 42:38

  Yeah, IV ketamine is interesting. It's it's not FDA cleared, and we won't see it FDA cleared because it's a generic drug. No, no, but but people use it, right? They they absolutely do use it. Um, I will say that dose is really key. So make sure if you are meeting someone for IV ketamine therapy that you ask what dose you're on and why. And they should give you a really good answer because that that literature is is pretty tight. Okay. But sprovato or nasal sketamine, okay, so sorry, going back to iv ketamine, one of the challenges is um to for ketamine to work, you have to kind of stay on it, like at least once every one to two weeks. And most iv ketamine clinics are cash only, and that can be uh cost prohibitive. Spravato is covered by most insurance, right? So then you're just talking a copay for the treatment, and that makes it fiscally viable. I think with all these things like neurostartimos therapy and uh spravato or nasal esketamine, I always see see three barriers to care. Awareness, which we talked about, geographic proximity, so you gotta find a clinic, and fiscal viability. And, you know, we shouldn't have a system of healthcare where your pathway to feeling better is like doing essentially a mortgage payment per month to try to get treatment. So, you know, before you go the ivy ketamine route, my recommendation is see if there's a spravado provider in your area and see about trying to get your insurance company to pay for your treatments so that you don't run into an issue where you have to decide between the cost and feeling better. Yeah. That's a great point.

  Dr. Kibby McMahon: 44:15

  Are there people who really shouldn't look into these? I I mean you mentioned contraindic indications, but are there types of patients or medical histories or or types of even depression or mental health conditions that really should be careful with either either type of treatment?

  Dr. Geoffrey Grammer: 44:34

  Yeah, I would say, you know, unfortunately, bipolar depression is one of those things that neither nasal eschetamine nor TMS has received FTA clearance or approval for. And just so folks know, even though bipolar depression has similar symptoms as major depressive disorder, we now know that those two conditions have to be treated differently.

  unknown: 44:56

  Right?

  Dr. Geoffrey Grammer: 44:56

  If you treat bipolar depression like you treat major depressive disorder, there was another study called the STEP BD trial that showed that it didn't really work and actually may have made people a little bit worse. It precipitated uh uh mixed mood states and rapid cycling. So um so bipolar depression, unfortunately, those would not, for most patients, be something that your insurance company would cover. There are some providers that may try to work with you if you've exhausted other options. Um, spravado or nasal esketamine can't be used in women who are either pregnant or breastfeeding, and it shouldn't be used in those with a history of uh strokes, uh, something called arteriovenous malformations, um, or with uncontrolled high blood pressure. Now, most providers will go through those things with you. Like again, every medication, every treatment's gonna have cautions and precautions and contraindications. They'll go through that with you. I will say TMS is a lot safer. There are some considerations we have in people with a history of of seizures that may require some special precautions or um, you know, uh again that metal above the neckline or medical devices within 30 centimeters of the coil. But again, your providers will go over. That's why you have to see your providers to make sure you can get it safe, safely done. Makes sense. That's so great. Again, and and this would be the one thing I, you know, uh I would just encourage people to do. It you you don't have to suffer anymore. And it it just it breaks my heart how many people I see like I'll give you a a couple of just anecdotes, right? Like for people to know what this is like. I have a patient I'm treating right now with um nasal es ketamine, and you know, she had been depressed for decades and and had the trail of life events that we often see in someone with chronic depression. And since she's been in treatment, she has been asymptomatic. And her con every week that I see her, she says, I wish I had known about this years ago. One of the first patients I ever treated with TMS therapy. Um a lot of people come in and say, I've been on every drug that's out there, and and they haven't, but it feels like it. She really has. She was also doing cognitive behavioral therapy and supportive psychotherapy with a social worker. And she had been through years of of psychoanalysis. So she had like really exhausted the continuum of care. And I remember it was one of the first patients I treated. I thought at the time, like, no way. Like, like this is this is, you know, I I was pessimistic. She completely remitted from her depressive symptoms in a way that she had never experienced before in her life. And to that psychotherapy thing we talked about before, she had this great metaphor. She said, It's like my pond has been drained, and now all those rocks that were covering issues I had to deal with, I can finally see and turn over. And she stayed in remission for five years. And she came back with a recurrent re return of symptoms because she had a dear family member who was um had a terminal illness. And we treated her again, she went back into remission, and she came back and thanked us and said, Because I wasn't depressed, I was there, you know, to be available to my family and to help everyone through the grieving process, and I was able to be present. So, like, there is no depression that is too severe to explore these modalities. There is no case that is too hopeless to get this. The only way to know if it's gonna work for you is if you access the treatment.

  Dr. Kibby McMahon: 48:39

  I'm just I'm uh totally speechless. That was a beautiful example that is so hopeful because there's so many people who are just like I I it just therapy doesn't work for me, medications don't work for me. I guess it's my personality. I guess life is hard, but it's it's so exciting to know that there are like available effective alternatives to what we all know. So thank you so much for this. Is there where can people find you or where can people find um neuronetics TMS or um the nasal ketam eschetamine?

  Dr. Geoffrey Grammer: 49:12

  Yeah, so if you go to neurostar.com, that can find you any TMS therapy provider in the country. Um and they will actually uh there's a uh way that you can click on a little link to try to you know get someplace that's close to you that you can actually search by insurance and so forth. It's really great. Um what I would also encourage people to do is uh if you Google uh Greenbrook Wellness Centers or Greenbrook TMS.com, um you can find a Greenbrook Center uh, you know, near where you live. Um and you know, we pride ourselves on kind of doing the heavy lifting with insurance. That's kind of our our claim to fame because we feel like if you're coming with depression, the last thing you should have to worry about is battling your insurance company to get approval. So we have an entire team that's dedicated to uh to doing that. And uh, you know, we would love to be part of your journey towards recovery. We really would.

  Dr. Kibby McMahon: 50:00

  That's fantastic. I'll link all of that in the show notes. So if anyone's curious, you could look at the the episode description. Thank you so much. This was such a fascinating conversation and so like I feel so energized and hopeful for all these different treatments. It's so great.

  Dr. Geoffrey Grammer: 50:16

  Well, thank you for the opportunity. I appreciate what you do and what your organization does. And uh, you know, I I think we're all in this battle together to help people feel better.

  Dr. Kibby McMahon: 50:26

  Oh, that's so great. Thank you. All right, listeners. Well, if you want to uh lift my treatment to resist a depression, leave a five-star review. Um, or share this with a friend, especially, and you know, spread the word about TMS and these and natal as because I mean these different ways that people could actually get treatment. So thank you so much, and we'll see you next week. By accessing this podcast, you acknowledge that the host of this podcast makes no warranty, guarantee, or representation as to the accuracy or sufficiency of information featured in this podcast. The information, opinions, and recommendations presented in this podcast are for general information purposes only, and any reliance on the information provided in this podcast is done at your own risk. This podcast and any and all content or services available on or through this podcast are provided for general, non-commercial informational purposes only, and do not constitute the practice of any medical or any professional judgment, advice, diagnosis, or treatment, and should not be considered or used as a substitute for the independent professional judgment, advice, diagnosis, or treatment of a duly licensed and qualified healthcare provider. In case of a medical emergency, you should immediately call 911. The host does not endorse, approve, recommend, or certify any information, product, process, service, or organization presented or mentioned in this podcast. And information from this podcast should not be referenced in any way to imply such approval or endorsement. Thank you.