The "First Line" Treatment Trap in Psychiatric Care
How brain stimulation treatment changes the lives of people with OCD...and its discontents.
I write about neuromodulation treatment frequently, and a criticism of existing data? The population studied is only treatment resistant patients. This article reviews OCD treatment with brain simulation via rTMS of various targets. I hope we will all learn something about science!
This is a newsletter by Owen Muir, M.D., and it’s worth subscribing to! This article is using an experimental new tool—included videos to explain stuff!
In the beginning, there were decisions made.
Like, for this article, defining terms!
Transcranial magnetic stimulation (TMS) involves taking an electromagnet and putting it close to your skull. When we repeat pulses, we put the “r” in front, to get rTMS.
Here is one picture that crushes explaining brain connectivity—how the brain syncs with itself in obsessive compulsive disorder:
The OCD brain is stuck in a loop of wrongness.
I just love that explanation. Onward:
Mapping the Brain with TMS
Transcranial = from outside the skull to inside the skull. Cranium and skull, samesies.
Magnetic = using Michael Faraday’s law of electromagnetic induction, a changing magnetic field can be created by running electricity in a coil of wire. This creates a magnetic field, and intern, it can induce an electrical current in a “nearby wire.”
Stimulation = the nearby wires, in the context of rTMS, are actually the long axons of the neurons of your brain.
The above axon is a long wire as far a a magnetic field is concerned…here is the right hand rule in video format!
Using the above understanding, we are able to measure the motor threshold by placing the magnetic field right on top of the Brain’s motor cortex. Like a reflex hammer can make a nerve fire to create movement in a muscle, you can use our electromagnet on your brain. The power of that magnetic pulse, given once, gives you a sense of the reactivity of the brain. Here is what that looks like in practice:
We are using the Brainsway H7 Stimulator on my head. I explain the process in a little bit of detail, but not too much, here, in 48 seconds.
Using the energy we calculate by finding the power necessary to make my toes move “three out of six total pulses”—which is the motor threshold that I explain in the video—we know the power for brain stimulation.
The treatment itself involves moving the helmet from the anchor point location— in this case, the place the foot is found to be on the brain, which is in the cleft between the two hemispheres:
The above distortion of the human body as It lounges on the brain? It is known as the “homunculus.” This is the layout of the body across the strip of brain that is the motor cortex. There is a similar sensory cortex mapping, with a very similar layout of the human body. Larger areas have more dense motor and sensory information—hands, lips, etc.
The treatment location is forward 4cm from the motor cortex location we mapped. Placed in this spot, it stimulates the “anti-correlated region with the dorsal anterior cingulate”—the OCD off switch!1
This mechanism Explanation is an Owen Muir opinion, but I think science backs it up. It was formed by logic, originally, but underscored in a number2 of papers3 as likely to be the right explanation.
One Hundred Years of Neuroscience Pays Off!
We have an ability to take 100 years of science and target a treatment4. We developed a way to use noninvasive stimulation of the brain to relieve the suffering of dreadful worry.
To be clear, this is not “experimental treatment.”
This is with FDA-cleared medical devices! We have randomized controlled trial evidence plus “phase-IV” data supporting the use of brain stimulation in treatment-resistant OCD.
But you notice I just said treatment resistant OCD? I didn’t say “OCD.” One might wonder—why that caveat? There are rules about false advertising! In my role as a Doctor, and also journalist, I tend to be careful.
We have biases. Research has biases. And payment models have significant biases. Those biases prevent providing what might be a greatest treatment to the most people at the lowest cost.
Why don't we do this for Everyone?
The ability to discover if transcranial magnetic stimulation works just as well in people presenting with obsessive compulsive disorder for the very first time, so they could possibly skip the whole oral medication futzing, or maybe even skip the psychotherapy first?
We don’t have the data. And that's because financial pressures prevented that data from being collected. Let me, as per usual, explain:
Drugs and therapy were developed first. The very first thing you develop to treat a disorder is the thing that will be given to people who have never gotten any treatment, because there is no other treatment.
It’s harder to do successful subsequent research in treatment naïve individuals.
Treatment resistance is a great way of selecting for a successful research study—in (likely) very effective interventions! If you're evaluating people who failed prior treatment, the chance that they're going to respond to a sham treatment is low. Thus, the need to enroll less patients—each of them are expensive—for a new intervention. Thus, studying new treatments in populations in which are likely to demonstrate a difference—without the problem of sham responders screwing up your outcome data—is an efficient way to demonstrate a Treatment Works.
The problem comes when insurance companies decide what they're going to pay for!
“oh, well the study only included treatment refractory patients. So we're only going to assume it works in treatment refectory individuals. Let us deny payment for everyone else.”
We don't enroll treatment refractory patients in studies because those are the only people for whom we believe a treatment will be effective. We do so because we want to demonstrate conclusively that the intervention is causally related to improvement in that illness.
We use study design to conclusively demonstrate that something works—it’s less good at answering the question who else would benefit.
Efficacy v. Effectiveness
The briefest explanation of the above intentional confusion? Healthcare payers are confusing efficacy trials with effectiveness trials. I would argue this is intentional at worst, or practically exactly what's happening in the worst possible way at best. FDA trials are efficacy trials.
Effectiveness studies take interventions already demonstrated to have efficacy—a causal relationship between Treatment and outcome—and then subsequently demonstrate that the efficacy translates into improvements in peoples lives in the real world.
These are different tasks.
Using efficacy trial inclusion criteria as the rationale to exclude patients from access to an efficacious treatment, we prevent doctors from gathering the data necessary to demonstrate effectiveness.5
We have already established safety, tolerability, and efficacy, in the same illness, with lower side effects, and lower total cost of care. And yet, exclusion criteria for insurance payments that are based on research study design exclude the patients who need a better treatment that is also safer.
This matters… a person who received accelerated OCD TMS had written an email to a scientist explaining why she felt the work mattered.6 This is what she wrote. This is not a testimonial. It is an explanation of why such treatment—accelerated— is important.
In the late 1980s, I was seven years old. One of my clearest memories from that age is sitting on the floor of my school gym, knees to my chest, pretending nothing was wrong as my classmates played a game of dodgeball, wishing that my gym teacher would tell my regular teacher that something was wrong.
I have been suicidal since I was 6 or 7 years old and I am now in my early 40s. I have tried every medication that exists. I have tried all the therapies. I was in - and failed - the original IV ketamine study. As an adult, I have been hospitalized 4 times, once for a three month course of ECT. I have attempted suicide 3 times, but not since the early 2000s. I am also a highly smart, funny, savvy person who manages to be a tenured special educator within the public school system and a board certified behavior analyst with close friends and family in between and on top of all the sadness and fear and suicidality.
Because of my history of suicidality and ECT, it was virtually impossible to find a qualified outpatient psychiatrist willing to work with me when my psychiatrist-therapist of many years quit. The one we found to replace her, quit. After that, literally, 80+ psychiatrists turned me down as a potential patient. Eventually, after a few years, someone referred me to my current psychiatrist, who took me on. We commenced regular (H1 coil LDLPFC) dTMS, which we finally stopped at 86 sessions, since it didn't do a whole lot.
And then, the accelerated protocol out of stanford came into being. And the world just flipped.
I cannot really put into coherent words how my world changed as a result. The first time we tried it, I sat in a little office doing nothing at all for the first 2 and a half days, and in the second half of the third day, I looked up and thought, why didn't I bring a book? I have so much free time in between sessions. Or some work. Or something. And that was the beginning of the end of all the fear.
Because the accelerated protocol means many things but most importantly, it means that I never have to be afraid of being hospitalized again. I never have to be afraid of psychiatrists or therapists quitting because my chronic suicidality is too much. It's 5 years later, and we are in the process of figuring out what's the least amount of prophylactic or maintenance TMS is needed but either way, there will never be a need for hospitalization for me again. I will never need to take a leave of absence from the work that I love again. I will never need to scare and terrify the people who I love, or to scare and terrify myself. I will never not be able to care for myself. There will just be a long weekendish of TMS and then my most genuine self will be back. This is obviously a tad simplistic...but it's also not. I have made it through 2 years now, years that included a pandemic, global chaos, a broken country, and a newish job...with no suicidality. And when the suicidalidality did return? We utilized the accelerated protocol and within 5 days, it receded. Predictably.
This is a massive statement. Hospitalization is terrifying, dangerous, humiliating and potentially far worse than any other option. After failing the original ketamine trial which led to my course of ECT, my psychiatrist-therapist of many years quit after hospitalizing me. For years afterward, I was terrified that I would be too much for anyone else, current psychiatrist included. The outpatient accelerated protocol takes that fear right out of the picture, because there will be no constant, chronic, overwhelming suicidality. 5 or 6 days kills it.
Outpatient accelerated TMS lets me keep being the fiercely independent, high functioning, thoughtful, joyful, useful person that I am.
This is more than a scientific question that should be answered accurately. And it's more than just an issue for billing. It is an issue of getting life-saving treatment— and the best current treatment— to people who need it.
This is a personal opinion, and not the explanation given by the inventor of the H7 coil, who insisted, last time we spoke, that the mechanism is the devices ability to directly stimulate the dACC.
Abnormal Resting-State Activities and Functional Connectivities of the Anterior and the Posterior Cortexes in Medication-Naïve Patients with Obsessive-Compulsive Disorder
Cheng Y, Xu J, Nie B, Luo C, Yang T, et al. (2013)Abnormal Resting-State Activities and Functional Connectivities of the Anterior and the Posterior Cortexes in Medication-Naïve Patients with Obsessive-Compulsive Disorder. PLOS ONE 8(6): e67478.https://doi.org/10.1371/journal.pone.0067478
J Psychiatr Res. Author manuscript; available in PMC 2022 Aug 4.
Published in final edited form as:
J Psychiatr Res. 2021 Jan; 132: 72–83.
Published online 2020 Oct 8. doi: 10.1016/j.jpsychires.2020.09.028
PMCID: PMC9351617
NIHMSID: NIHMS1636030
PMID: 33068817
pairing functional magnetic resonance imaging to show us what the brain is doing in real time, plus the physics of electromagnetism, and use what we learned from brain imaging to confirm what we learned from treatment studies.
This includes those who have never gotten any treatment before. It is the same illness! It is true that we don't yet know, lacking an efficacy trial, that the intervention is biologically low active in treatment naïve individuals, but you don't need to answer that question in a randomized controlled trial design.
and we discussed the “opt-in option” of rewriting it such that it would be as anonymized as she would want it to be.
Thanks for this! I’m curious if you have any thoughts about augmentation of therapy with multiple concurrent targets? I saw quite good results from my dmPFC treatment for OCD (44 sessions) and UCSF then added the right OFC with cTBS. From what I can tell no one really know what the non-linear effects are from potentially combining targets. Not sure if you had any visibility into that or thoughts from your practice? This is mainly curiosity but also to just inform any approaches I may take for maintainance therapy.