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Owen Muir, MD, believes TMS ought to come before antidepressants for many teens with depression, but does the FDA agree with him?
Publication Date: 11/10/2025
Duration: 13 minutes, 39 seconds
Transcript:
KELLIE NEWSOME: The FDA has a new clearance for TMS. It hasn’t made many headlines, but some think it changes the game for adolescent depression. Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003.
CHRIS AIKEN: I’m Chris Aiken, the editor in chief of The Carlat Report.
KELLIE NEWSOME: And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.
CHRIS AIKEN: I’ve always wished I could practice psychiatry in 1963, because that’s around when insulin coma therapy and frontal lobotomies were on the decline, rapidly replaced by safer and more effective therapies like psychopharmacology. I say more effective, because there was a small signal that these older therapies worked, at least in terms of reducing symptoms, at least worked enough that psychiatrists argued for their utility well into our current age. The last paper that argued for frontal lobotomy in schizophrenia was a case series from 1997 (by this time the name had changed to leucotomy), and as late as 2013, we find a case report on the efficacy of insulin coma therapy in refractory depression. With hindsight, these changes are dramatic, they are revolutionary, but for practicing psychiatrists, the changing of the guards was a gradual process, quietly hashed out in the back pages of medical journals and sporadic conference debates. Which means we could be in a revolution right now and not even know it. Here are some contenders….
CHRIS AIKEN: I’m Chris Aiken, the editor in chief of The Carlat Report.
KELLIE NEWSOME: And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.
CHRIS AIKEN: I’ve always wished I could practice psychiatry in 1963, because that’s around when insulin coma therapy and frontal lobotomies were on the decline, rapidly replaced by safer and more effective therapies like psychopharmacology. I say more effective, because there was a small signal that these older therapies worked, at least in terms of reducing symptoms, at least worked enough that psychiatrists argued for their utility well into our current age. The last paper that argued for frontal lobotomy in schizophrenia was a case series from 1997 (by this time the name had changed to leucotomy), and as late as 2013, we find a case report on the efficacy of insulin coma therapy in refractory depression. With hindsight, these changes are dramatic, they are revolutionary, but for practicing psychiatrists, the changing of the guards was a gradual process, quietly hashed out in the back pages of medical journals and sporadic conference debates. Which means we could be in a revolution right now and not even know it. Here are some contenders….
- The first is antipsychotics in delirium. This year, the APA updated their practice guidelines for delirium, downgrading antipsychotics to a treatment of last resort. The changing of the guards came on top of numerous meta-analyses and large controlled trials show no discernible benefit with antipsychotics in delirium and some well-known risks. So far, the reaction on the professional level has been mixed, with some accusing the APA committee of being out of touch with the realities of everyday practice, and others retorting that the trials enrolled the wrong patients, looked at the wrong outcomes, or that we have to use antipsychotics until something better comes along.
- The second quiet revolution is antidepressants in child and adolescent depression. Over 34 placebo-controlled trials have tested these medications in this age group, and only one has come out with clear efficacy: fluoxetine, Prozac. Runners up include the FDA approved escitalopram, approved down to age 12, and the unapproved sertraline, both of which have a mix of positive and negative data in this age group.
Now, I hope you don't take what I'm saying the wrong way. I am not saying that there's some connection between lobotomy or insulin comatherapy and antipsychotics in delirium or antidepressants in children, not by any stretch. These two don't match up in their overall profiles, their methods, or their risks at all. I am saying that I think our forebearers had good intentions when they used these treatments, and they believe these treatments worked based on the evidence they had. We are not so different from them, and I think we need to be on the lookout for treatments we use every day that really don't work despite our best intentions.
KELLIE NEWSOME: At this point, we’d like to read you the list of antidepressants that did not pass muster in youth depression, but it’s too long. Suffice it to say that it includes the tricyclics and nearly all modern antidepressants – including the newest ones, levomilnacipran, vilazodone, and vortioxetine – just about all except trazodone and bupropion. Those are still uncharted territory. So, outside of fluoxetine, why do we use antidepressants in children?
CHRIS AIKEN: I think the assumption is that – if fluoxetine and escitalopram worked – then most of the others must work as well – and there was something wrong with the trials, not the meds. The trials were very well designed, and the only fault we can find is that they have a high placebo response rate that may have made it difficult to detect any medication effect. Whichever side of this debate you choose to stand on, I’d be careful about discontinuing antidepressants in youth. If you do, do it slowly, as antidepressant withdrawal can trigger depression.
KELLIE NEWSOME: Well, judging by the numbers, it seems a lot of clinicians are on the side of antidepressants. Around 1 in 10 adolescents in the US have depression, and about half of them are prescribed antidepressants. But you’re suggesting we’re in the midst of a revolution, that this is about to change.
CHRIS AIKEN: I’m not a child psychiatrist and don’t have the expertise to make that kind of judgment, but I’m going to talk to someone who is. Owen Muir is a child and adolescent – and adult – psychiatrist and Chief Medical Officer at Radial, a practice that specializes in TMS and other interventional therapies. When I asked him who the ideal candidate was for TMS, his answer surprised me and got me thinking. Owen, of all the patients that you see, who is the best candidate for TMS?
OWEN MUIR: The younger the person is, the closer, and closer, TMS or transcranial magnetic stimulation gets to being the first thing I'd recommend.
CHRIS AIKEN: Younger like children, that's not what I was expecting.
OWEN MUIR: Adolescents are in crisis frequently when they're coming to see a psychiatrist. Like if it wasn't that big of a problem, they'd talk to their parents, maybe they'd talk to their friends. But by the time they're seeing a mental health professional, it's a real problem. For adolescents, the risk of attempting suicide is terrifyingly high. When we look at data from the CDC in 2023, 13% of high school girls will attempt to end their life by suicide, and 7% of adolescent boys.
CHRIS AIKEN: So that's like 13% of all high school girls?
OWEN MUIR: Yes.
CHRIS AIKEN: Okay. So these are really alarming rates, and why does that draw you to TMS?
OWEN MUIR: TMS works. It's an effective treatment that will make depression and particularly suicidality get better in most people we use it with, and increasingly quickly. And I don't wanna worry, right? As someone who is a healer, and someone's bringing their child to me to heal them from despair, that could lead to death. I want that to be over quickly.
CHRIS AIKEN: Alright. But what about antidepressants? Do they work in children? I mean, fluoxetine is FDA-approved.
OWEN MUIR: It's, and it's probably saved more lives than I could count. However, every oral antidepressant medicine in youth has a black box warning for increasing suicidal thinking. So, a quick moment for every death by suicide, another 27 will self-report attempts at suicide, and another 273 will be thinking about suicide actively, and so when we talk about the number of suicide attempts that we see in young people, the overwhelming majority of those kids will not die by suicide. Awesome, but many of them will be miserable, and for a long time. So when we're thinking about treatments for adolescent despair, some of which is depression, but not all, we really wanna do something that is highly likely to work quickly.
CHRIS AIKEN: And you say adolescence, I remember the TMS got FDA approved for younger patients. What age does it go down to now?
OWEN MUIR: The FDA label, TMS treatment as an adjuvant to first-line treatment for depression, which, remember, includes psychotherapy, is down to age 15, and that approval was based on post-marketing data in the real world at a massive scale. So, we're talking about 10,000 kids who were submitted to the FDA for that post-marketing data set.
KELLIE NEWSOME: Let’s pause for a preview of the CME quiz for this episode. Earn CME for each episode through the link in the show notes.
KELLIE NEWSOME: At this point, we’d like to read you the list of antidepressants that did not pass muster in youth depression, but it’s too long. Suffice it to say that it includes the tricyclics and nearly all modern antidepressants – including the newest ones, levomilnacipran, vilazodone, and vortioxetine – just about all except trazodone and bupropion. Those are still uncharted territory. So, outside of fluoxetine, why do we use antidepressants in children?
CHRIS AIKEN: I think the assumption is that – if fluoxetine and escitalopram worked – then most of the others must work as well – and there was something wrong with the trials, not the meds. The trials were very well designed, and the only fault we can find is that they have a high placebo response rate that may have made it difficult to detect any medication effect. Whichever side of this debate you choose to stand on, I’d be careful about discontinuing antidepressants in youth. If you do, do it slowly, as antidepressant withdrawal can trigger depression.
KELLIE NEWSOME: Well, judging by the numbers, it seems a lot of clinicians are on the side of antidepressants. Around 1 in 10 adolescents in the US have depression, and about half of them are prescribed antidepressants. But you’re suggesting we’re in the midst of a revolution, that this is about to change.
CHRIS AIKEN: I’m not a child psychiatrist and don’t have the expertise to make that kind of judgment, but I’m going to talk to someone who is. Owen Muir is a child and adolescent – and adult – psychiatrist and Chief Medical Officer at Radial, a practice that specializes in TMS and other interventional therapies. When I asked him who the ideal candidate was for TMS, his answer surprised me and got me thinking. Owen, of all the patients that you see, who is the best candidate for TMS?
OWEN MUIR: The younger the person is, the closer, and closer, TMS or transcranial magnetic stimulation gets to being the first thing I'd recommend.
CHRIS AIKEN: Younger like children, that's not what I was expecting.
OWEN MUIR: Adolescents are in crisis frequently when they're coming to see a psychiatrist. Like if it wasn't that big of a problem, they'd talk to their parents, maybe they'd talk to their friends. But by the time they're seeing a mental health professional, it's a real problem. For adolescents, the risk of attempting suicide is terrifyingly high. When we look at data from the CDC in 2023, 13% of high school girls will attempt to end their life by suicide, and 7% of adolescent boys.
CHRIS AIKEN: So that's like 13% of all high school girls?
OWEN MUIR: Yes.
CHRIS AIKEN: Okay. So these are really alarming rates, and why does that draw you to TMS?
OWEN MUIR: TMS works. It's an effective treatment that will make depression and particularly suicidality get better in most people we use it with, and increasingly quickly. And I don't wanna worry, right? As someone who is a healer, and someone's bringing their child to me to heal them from despair, that could lead to death. I want that to be over quickly.
CHRIS AIKEN: Alright. But what about antidepressants? Do they work in children? I mean, fluoxetine is FDA-approved.
OWEN MUIR: It's, and it's probably saved more lives than I could count. However, every oral antidepressant medicine in youth has a black box warning for increasing suicidal thinking. So, a quick moment for every death by suicide, another 27 will self-report attempts at suicide, and another 273 will be thinking about suicide actively, and so when we talk about the number of suicide attempts that we see in young people, the overwhelming majority of those kids will not die by suicide. Awesome, but many of them will be miserable, and for a long time. So when we're thinking about treatments for adolescent despair, some of which is depression, but not all, we really wanna do something that is highly likely to work quickly.
CHRIS AIKEN: And you say adolescence, I remember the TMS got FDA approved for younger patients. What age does it go down to now?
OWEN MUIR: The FDA label, TMS treatment as an adjuvant to first-line treatment for depression, which, remember, includes psychotherapy, is down to age 15, and that approval was based on post-marketing data in the real world at a massive scale. So, we're talking about 10,000 kids who were submitted to the FDA for that post-marketing data set.
KELLIE NEWSOME: Let’s pause for a preview of the CME quiz for this episode. Earn CME for each episode through the link in the show notes.
1. In March 2024, the FDA extended the clearance of TMS in major depressive disorder down to what age level?
A. Age 12
B. Age 18
C. Age 15
D. Age 6
CHRIS AIKEN: If we look at antidepressants, a little over 20 of them have been studied for depression, and really only fluoxetine passed. I mean, just a few months ago, vortioxetine, the great Trintellix, tried and didn't make it. So maybe citalopram or escitalopram is kind of 50/50, but we really don't have much of a strong signal with antidepressants even working, in addition, you have this suicide risk, which I understand kind of tapers off as you get older. Maybe by age 25 it starts to go down, so you're saying we should think of the opposite taper with TMS, that the younger you are, the more likely TMS is gonna be a better choice than an antidepressant. Am I hearing you right?
OWEN MUIR: I think adolescents are probably feeling really smug if they listen to this, because, oh gosh, we, adults, just don't know what we're talking about. I'm joking a little bit, but if you're running an adolescent trial, like nothing adolescents like more than sticking it to clueless old people, and depression studies do a good job of that because it turns out adolescents, on average, respond well to people being interested in them and caring. And that's what we see in studies.
CHRIS AIKEN: Ah, so maybe that's why there's such a high placebo response rate in pediatric studies of depression.
OWEN MUIR: Exactly. Now, at the same time, we really wanna make sure if we're worried about somebody, and I worry about impulsive young people, because they can do things that adults would never consider a good idea, think back to everything you did in your youth.
CHRIS AIKEN: Whether they have bipolar or not.
OWEN MUIR: I remember thinking it was a good idea as a teenager to open a popcorn tin by throwing it out of a moving car with my friends. Adolescents do dumb stuff, routinely, because their brains, you know, we talk about them not being fully developed, but like thinking that something is a bad idea and stopping, is not an adolescent's strong point.
CHRIS AIKEN: And that's where the suicide risk comes in.
OWEN MUIR: Exactly. So when adolescents are in despair, they haven't had the experience that adults have had of it passing, especially if it's the first time.
CHRIS AIKEN: Okay, so when it comes to adolescent depression, we have better evidence for psychotherapy for TMS, and antidepressants are kind of on the marginal side of the evidence there.
OWEN MUIR: The only large-scale data that says an oral medicine works better than a placebo, AKA carrying alone, for adolescents is for fluoxetine, the first drug in the SSRI class. So we've got one drug for adolescent depression. It's hard to show a difference in adolescent depression.
KELLIE NEWSOME: Owen Muir is a clinical assistant professor at the Menninger Department of Psychiatry and Behavioral Sciences. He has the following conflict of interest to disclose. He has received research funding from Brainsway and Magnus, manufacturers of TMS devices. He practices and works as CMO at Radial, and is also CMO of Neurolief, which is developing a home-based neuromodulation therapy. In his limited spare time, he runs the popular Frontier Psychiatrist blog and podcast on Substack. Psychiatric revolutions are ripe for opinions, and we’d like to hear your take on these controversies. Write us at asktheeditor@thecarlatreport.com, or join the conversation on Dr. Aiken’s Daily Psych feed. Search for ChrisAikenMD on LinkedIn, Twitter, Facebook, Bluesky, and Threads.
CHRIS AIKEN: If we look at antidepressants, a little over 20 of them have been studied for depression, and really only fluoxetine passed. I mean, just a few months ago, vortioxetine, the great Trintellix, tried and didn't make it. So maybe citalopram or escitalopram is kind of 50/50, but we really don't have much of a strong signal with antidepressants even working, in addition, you have this suicide risk, which I understand kind of tapers off as you get older. Maybe by age 25 it starts to go down, so you're saying we should think of the opposite taper with TMS, that the younger you are, the more likely TMS is gonna be a better choice than an antidepressant. Am I hearing you right?
OWEN MUIR: I think adolescents are probably feeling really smug if they listen to this, because, oh gosh, we, adults, just don't know what we're talking about. I'm joking a little bit, but if you're running an adolescent trial, like nothing adolescents like more than sticking it to clueless old people, and depression studies do a good job of that because it turns out adolescents, on average, respond well to people being interested in them and caring. And that's what we see in studies.
CHRIS AIKEN: Ah, so maybe that's why there's such a high placebo response rate in pediatric studies of depression.
OWEN MUIR: Exactly. Now, at the same time, we really wanna make sure if we're worried about somebody, and I worry about impulsive young people, because they can do things that adults would never consider a good idea, think back to everything you did in your youth.
CHRIS AIKEN: Whether they have bipolar or not.
OWEN MUIR: I remember thinking it was a good idea as a teenager to open a popcorn tin by throwing it out of a moving car with my friends. Adolescents do dumb stuff, routinely, because their brains, you know, we talk about them not being fully developed, but like thinking that something is a bad idea and stopping, is not an adolescent's strong point.
CHRIS AIKEN: And that's where the suicide risk comes in.
OWEN MUIR: Exactly. So when adolescents are in despair, they haven't had the experience that adults have had of it passing, especially if it's the first time.
CHRIS AIKEN: Okay, so when it comes to adolescent depression, we have better evidence for psychotherapy for TMS, and antidepressants are kind of on the marginal side of the evidence there.
OWEN MUIR: The only large-scale data that says an oral medicine works better than a placebo, AKA carrying alone, for adolescents is for fluoxetine, the first drug in the SSRI class. So we've got one drug for adolescent depression. It's hard to show a difference in adolescent depression.
KELLIE NEWSOME: Owen Muir is a clinical assistant professor at the Menninger Department of Psychiatry and Behavioral Sciences. He has the following conflict of interest to disclose. He has received research funding from Brainsway and Magnus, manufacturers of TMS devices. He practices and works as CMO at Radial, and is also CMO of Neurolief, which is developing a home-based neuromodulation therapy. In his limited spare time, he runs the popular Frontier Psychiatrist blog and podcast on Substack. Psychiatric revolutions are ripe for opinions, and we’d like to hear your take on these controversies. Write us at asktheeditor@thecarlatreport.com, or join the conversation on Dr. Aiken’s Daily Psych feed. Search for ChrisAikenMD on LinkedIn, Twitter, Facebook, Bluesky, and Threads.
