Hi Sable, I’m a TMS (+EEG) researcher. I’m happy to see some TMS discussed here and this is a nice introductory writeup. If you had any specific questions about TMS or the therapy I’d be happy to answer them or point you in the right direction. Depression is not my personal area of study or expertise, but it’s hard not to know a lot about depression treatment if you study TMS for a living because it’s the most successful application of the technique.
Two specific things you mentioned—first, that TMS depression therapy does not require or use an MRI. It’s right of you to point this out, because doesn’t it seem obvious that if we targeted based on the brain’s structural or functional properties we could give better therapy? The answer is yes, and it’s frankly a miracle that TMS works for depression without this kind of targeting. Still, there is still a strong intuition that the current therapy leaves a lot on the table, and lots of labs are studying how to make it better in depression, other dysfunctions and in healthy cognition. This is close to my area of research, which is broadly to investigate what spatial or temporal information about the brain is useful to make a given therapy or research intervention better and develop techniques for actually using it.
The second thing I noticed was your frustration that you have to fail medications to get approved for TMS. This is super frustrating, but I think it’s just about caution in the medical community rather than any first order conspiracy by pharma. My sense is that medications still work better for most people, where “work better” is a conjunction between the raw effectiveness of the therapy and treatment adherence (which as you mentioned is a not-convenient aspect of TMS for depression). A related issue is that the medical community knows how well medications work and so are in some kind of Hippocratic contract to force people try that first before offering the “experimental” thing. Even though it’s over a decade old now, TMS depression therapy is still considered pretty experimental. Epecially the kind it sounds like you got, which is an accelerated course.
I’m really glad the therapy worked for you, thanks for bringing this content to LessWrong.
My biggest question is probably what the distribution looks like for people who get TMS for depression—how many of them are “cured” in the sense that they never need TMS again? How many need it again after a year? Two years? And so on.
Took me a while to get back to this question. I didn’t know the answer so I looked up some papers. The short answer is, knowing this requires long follow-up periods which studies are generally not good at so we don’t have great answers. Definitely a significant number of people don’t stay better.
The longer answer is, probably about half of people need some form of maintenance treatment to stay non-depressed for more than a year, but our view of this is very confounded. Some studies have used normal antidepressant medications for maintenance, and some studies have tried additional rounds of TMS, both of which work really well. Up to a third of patients experience “symptom worsening” meaning that after an initial improvement from TMS, their symptoms actually get worse than when they started, but apparently more TMS can fix this in most people? I wasn’t completely sure what they were saying here. So yeah, it isn’t great. A lot of people need maintenance of some kind. This could very well correlate with whether your depression is the “life circumstances” kind or the “intrinsic brain chemistry” kind, not that we have a great handle on differentiating those two either.
Furthermore, (1) there are a few modes of TMS therapy out there, including most notably the accelerated course, and there may be different relapse rates across these treatment modes. There is some handwaving that the accelerated course may be more effective in this regard but I don’t think we know yet. And (2) another important issue with interpreting these data is that many of the studies are done on people who are treatment resistant, such as yourself. It’s unclear how much the results translate to the general population of depressed people.
Overall this is probably not a very satisfying answer, I don’t really have the specialist inside view on this one.
FYI the most targeted paper I found on this topic is the citation below. Note that it’s from 2016. There is probably something more recent, I just didn’t have more time to dig.
Sackeim, H. A. (2016). Acute continuation and maintenance treatment of major depressive episodes with transcranial magnetic stimulation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, 9(3), 313-319.
This isn’t directly related to TMS, but I’ve been trying to get an answer to this question for years, and maybe you have one.
When doing TMS, or any depression treatment, or any supplementation experiment, etc. it would make sense to track the effects objectively (in addition to, not as a replacement for subjective monitoring). I haven’t found any particularly good option for this, especially if I want to self-administer it most days. Quantified mind comes close, but it’s really hard to use their interface to construct a custom battery and an indefinite experiment.
Hey, I remember your medical miracle post. I enjoyed it!
”Objectively” for me would translate to “biomarker” i.e., a bio-physical signal that predicts a clinical outcome. Note that for depression and many psychological issues this means that we find the biomarkers by asking people how they feel...but maybe this is ok because we do huge studies with good controls, and the biomarkers may take on a life of their own after they are identified.
I’m assuming you mean biomarkers for psychological / mental health outcomes specifically. This is spiritually pretty close to what my lab studies—ways to predict how TMS will affect individuals, and adjust it to make it work better in each person. Our philosophy—which I had to think about for a bit to even articulate, it’s so baked into our thinking—is that the effects of an intervention will manifest most reliably in reactions to very simple cognitive tasks like vigilance, working memory, and so on. Most serious health issues impact your reaction times, accuracy, bias, etc. in subtle but statistically reliable ways. Measuring these with random sampling from a phone app and doing good statistics on the data is probably your best bet for objectively assessing interventions. Maybe that is what Quantified Mind does, I’m not sure?
The short answer is that if this were easy, it would already be popular, because we clearly need it. A lot of academic labs and industry people are trying to do this all the time. There is growing success, but it’s slow growing and fraught with non-replicable work.
Not my medical miracle post, just my comment on it.
“Objectively” for me would translate to “biomarker” i.e., a bio-physical signal that predicts a clinical outcome.
Yes, though I wouldn’t restrict it to “clinical” because I care about non-medical outcomes, and “bio-physical” seems restrictive, though based on your example, that seems to be just my interpretation of the term.
Note that for depression and many psychological issues this means that we find the biomarkers by asking people how they feel
These are legitimate biomarkers, but they’re not what I want, and I’m struggling to explain specifically why; the two things that come up are that they have low statistical power and they’re a particularly lagging indicator (imagine for contrast e.g. being able to tell whether an antidepressant would work for you after taking it for a week, even if it takes two months to feel the effects). They’re fine and useful for statistics, and even for measuring the effectiveness of a treatment in an individual, but a lot less useful for experimenting.
I’m assuming you mean biomarkers for psychological / mental health outcomes specifically. This is spiritually pretty close to what my lab studies—ways to predict how TMS will affect individuals, and adjust it to make it work better in each person.
That sounds really cool. I’m assuming there’s nothing actionable available right now for patients?
Our philosophy [...] is that the effects of an intervention will manifest most reliably in reactions to very simple cognitive tasks like vigilance, working memory, and so on. Most serious health issues impact your reaction times, accuracy, bias, etc. in subtle but statistically reliable ways.
Yep. This is basically what I’m hoping to monitor in myself. For example, better vigilance might translate to better focus on work tasks, or better selective attention might imply better impulse control.
Measuring these with random sampling from a phone app and doing good statistics on the data is probably your best bet for objectively assessing interventions. Maybe that is what Quantified Mind does, I’m not sure?
QM doesn’t work so well on phone and hasn’t been updated on years and has major UX issues for my use case that makes it too hard to work with. It also doesn’t expose the raw statistics. Cognifit (the only app I’ve found that does assessment and not just “brain training”) reports even less.
Do you have a specific app that you know of?
The short answer is that if this were easy, it would already be popular, because we clearly need it. A lot of academic labs and industry people are trying to do this all the time. There is growing success, but it’s slow growing and fraught with non-replicable work.
I don’t think this is true. My alternative hypothesis (which I think is also compatible with the data) is that it’s not hard, but there’s no money in it, so there’s not much commercial “free energy” making it happen, and that it’s tedious, so there’s not much hobbyist “free energy”, and academia is slow as things like this.
Hi Sable, I’m a TMS (+EEG) researcher. I’m happy to see some TMS discussed here and this is a nice introductory writeup. If you had any specific questions about TMS or the therapy I’d be happy to answer them or point you in the right direction. Depression is not my personal area of study or expertise, but it’s hard not to know a lot about depression treatment if you study TMS for a living because it’s the most successful application of the technique.
Two specific things you mentioned—first, that TMS depression therapy does not require or use an MRI. It’s right of you to point this out, because doesn’t it seem obvious that if we targeted based on the brain’s structural or functional properties we could give better therapy? The answer is yes, and it’s frankly a miracle that TMS works for depression without this kind of targeting. Still, there is still a strong intuition that the current therapy leaves a lot on the table, and lots of labs are studying how to make it better in depression, other dysfunctions and in healthy cognition. This is close to my area of research, which is broadly to investigate what spatial or temporal information about the brain is useful to make a given therapy or research intervention better and develop techniques for actually using it.
The second thing I noticed was your frustration that you have to fail medications to get approved for TMS. This is super frustrating, but I think it’s just about caution in the medical community rather than any first order conspiracy by pharma. My sense is that medications still work better for most people, where “work better” is a conjunction between the raw effectiveness of the therapy and treatment adherence (which as you mentioned is a not-convenient aspect of TMS for depression). A related issue is that the medical community knows how well medications work and so are in some kind of Hippocratic contract to force people try that first before offering the “experimental” thing. Even though it’s over a decade old now, TMS depression therapy is still considered pretty experimental. Epecially the kind it sounds like you got, which is an accelerated course.
I’m really glad the therapy worked for you, thanks for bringing this content to LessWrong.
That’s awesome that you’re doing that research!
My biggest question is probably what the distribution looks like for people who get TMS for depression—how many of them are “cured” in the sense that they never need TMS again? How many need it again after a year? Two years? And so on.
Took me a while to get back to this question. I didn’t know the answer so I looked up some papers. The short answer is, knowing this requires long follow-up periods which studies are generally not good at so we don’t have great answers. Definitely a significant number of people don’t stay better.
The longer answer is, probably about half of people need some form of maintenance treatment to stay non-depressed for more than a year, but our view of this is very confounded. Some studies have used normal antidepressant medications for maintenance, and some studies have tried additional rounds of TMS, both of which work really well. Up to a third of patients experience “symptom worsening” meaning that after an initial improvement from TMS, their symptoms actually get worse than when they started, but apparently more TMS can fix this in most people? I wasn’t completely sure what they were saying here. So yeah, it isn’t great. A lot of people need maintenance of some kind. This could very well correlate with whether your depression is the “life circumstances” kind or the “intrinsic brain chemistry” kind, not that we have a great handle on differentiating those two either.
Furthermore, (1) there are a few modes of TMS therapy out there, including most notably the accelerated course, and there may be different relapse rates across these treatment modes. There is some handwaving that the accelerated course may be more effective in this regard but I don’t think we know yet. And (2) another important issue with interpreting these data is that many of the studies are done on people who are treatment resistant, such as yourself. It’s unclear how much the results translate to the general population of depressed people.
Overall this is probably not a very satisfying answer, I don’t really have the specialist inside view on this one.
FYI the most targeted paper I found on this topic is the citation below. Note that it’s from 2016. There is probably something more recent, I just didn’t have more time to dig.
Sackeim, H. A. (2016). Acute continuation and maintenance treatment of major depressive episodes with transcranial magnetic stimulation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, 9(3), 313-319.
This isn’t directly related to TMS, but I’ve been trying to get an answer to this question for years, and maybe you have one.
When doing TMS, or any depression treatment, or any supplementation experiment, etc. it would make sense to track the effects objectively (in addition to, not as a replacement for subjective monitoring). I haven’t found any particularly good option for this, especially if I want to self-administer it most days. Quantified mind comes close, but it’s really hard to use their interface to construct a custom battery and an indefinite experiment.
Do you know of anything?
Hey, I remember your medical miracle post. I enjoyed it!
”Objectively” for me would translate to “biomarker” i.e., a bio-physical signal that predicts a clinical outcome. Note that for depression and many psychological issues this means that we find the biomarkers by asking people how they feel...but maybe this is ok because we do huge studies with good controls, and the biomarkers may take on a life of their own after they are identified.
I’m assuming you mean biomarkers for psychological / mental health outcomes specifically. This is spiritually pretty close to what my lab studies—ways to predict how TMS will affect individuals, and adjust it to make it work better in each person. Our philosophy—which I had to think about for a bit to even articulate, it’s so baked into our thinking—is that the effects of an intervention will manifest most reliably in reactions to very simple cognitive tasks like vigilance, working memory, and so on. Most serious health issues impact your reaction times, accuracy, bias, etc. in subtle but statistically reliable ways. Measuring these with random sampling from a phone app and doing good statistics on the data is probably your best bet for objectively assessing interventions. Maybe that is what Quantified Mind does, I’m not sure?
The short answer is that if this were easy, it would already be popular, because we clearly need it. A lot of academic labs and industry people are trying to do this all the time. There is growing success, but it’s slow growing and fraught with non-replicable work.
Not my medical miracle post, just my comment on it.
Yes, though I wouldn’t restrict it to “clinical” because I care about non-medical outcomes, and “bio-physical” seems restrictive, though based on your example, that seems to be just my interpretation of the term.
These are legitimate biomarkers, but they’re not what I want, and I’m struggling to explain specifically why; the two things that come up are that they have low statistical power and they’re a particularly lagging indicator (imagine for contrast e.g. being able to tell whether an antidepressant would work for you after taking it for a week, even if it takes two months to feel the effects). They’re fine and useful for statistics, and even for measuring the effectiveness of a treatment in an individual, but a lot less useful for experimenting.
That sounds really cool. I’m assuming there’s nothing actionable available right now for patients?
Yep. This is basically what I’m hoping to monitor in myself. For example, better vigilance might translate to better focus on work tasks, or better selective attention might imply better impulse control.
QM doesn’t work so well on phone and hasn’t been updated on years and has major UX issues for my use case that makes it too hard to work with. It also doesn’t expose the raw statistics. Cognifit (the only app I’ve found that does assessment and not just “brain training”) reports even less.
Do you have a specific app that you know of?
I don’t think this is true. My alternative hypothesis (which I think is also compatible with the data) is that it’s not hard, but there’s no money in it, so there’s not much commercial “free energy” making it happen, and that it’s tedious, so there’s not much hobbyist “free energy”, and academia is slow as things like this.