I wanted to do this episode, because when I did my episodes on electroconvulsive therapy (or ECT), I feel like I sounded a tiddly-bit dismissive of it, and I wanted to clarify what I meant when I said, “TMS, short for Transcranial Magnetic Stimulation of the Brain, as of yet is not nearly as efficacious as ECT.” If you haven’t listened to the ECT episodes, you should still be able to follow this discussion, so don’t feel left out. I give a history of TMS development, discuss some of its approved indications, and outline three important ways that TMS is not as effective as ECT. I also mention some promising evidence that TMS is gaining rapidly in at least two of these ways.
Please leave feedback at https://www.psydactic.com.
References and readings (when available) are posted at the end of each episode transcript, located at psydactic.buzzsprout.com. All opinions expressed in this podcast are exclusively those of the person speaking and should not be confused with the opinions of anyone else. We reserve the right to be wrong. Nothing in this podcast should be treated as individual medical advice.
I wanted to do this episode, because when I did my episodes on electroconvulsive therapy (or ECT), I feel like I sounded a tiddly-bit dismissive of it, and I wanted to clarify what I meant when I said, “TMS, short for Transcranial Magnetic Stimulation of the Brain, as of yet is not nearly as efficacious as ECT.” If you haven’t listened to the ECT episodes, you should still be able to follow this discussion, so don’t feel left out. I give a history of TMS development, discuss some of its approved indications, and outline three important ways that TMS is not as effective as ECT. I also mention some promising evidence that TMS is gaining rapidly in at least two of these ways.
Please leave feedback at https://www.psydactic.com.
References and readings (when available) are posted at the end of each episode transcript, located at psydactic.buzzsprout.com. All opinions expressed in this podcast are exclusively those of the person speaking and should not be confused with the opinions of anyone else. We reserve the right to be wrong. Nothing in this podcast should be treated as individual medical advice.
TMS - Brief History and Development
Welcome to PsyDactic - Residency Edition - Your podcast resource to survive and thrive in your psych residency.
I am Dr. O’Leary, and as of this recording I am a 2nd Year Resident in the National Capital Consortium Psychiatry Residency Program. However, make no mistake, I do not speak for this program, nor do I speak for the Department of Defense or the Federal Government or anyone else for that matter. What I say is my opinion, and I reserve the right to be wrong, so trust me at your own risk. It’s a risk some are willing to take.
In addition, I often use colorful language and strange, sometimes twisted metaphors. It’s a style choice. I want to make my podcasts more fun for myself and the listener. Plus, it is who I am, so you get an honest glimpse into my mind. Some of this language may seem insensitive, but it is not my intent to offend, dismiss, or belittle anyone.
I wanted to do this episode, because when I did my episodes on electroconvulsive therapy (or ECT), I feel like I sounded a tiddly-bit dismissive of it, and I wanted to clarify what I meant when I said, “TMS (short for Transcranial Magnetic Stimulation of the Brain) as of yet is not nearly as efficacious as ECT.” If you haven’t listened to the ECT episodes, you should still be able to follow this discussion, so don’t feel left out. There are three important ways that TMS is not as effective as ECT and there is some promising evidence that TMS is gaining rapidly in at least two of these ways.
First, TMS is not used for as many indications as ECT. Secondly, as I produce this podcast, TMS is not as effective as ECT for their overlapping indications. Finally, TMS is not as rapidly effective. In 2020, researchers at Stanford published results of a protocol for TMS that is promising to close the gap on effectiveness and vastly reduce the time to remission in patients with treatment resistant depression. They call it the Stanford Accelerated Intelligent Neuromodulation Therapy or SAINT for short.
But that is getting ahead of ourselves. To start, I think you deserve a quick primer on what TMS is, how it was developed, and what these recent advances actually are, so I’ll dedicate this episode to that. In future episodes, I’ll prognosticate in more detail the current trajectory of TMS.
Unlike ECT, TMS was NOT developed initially as a treatment modality. It was used for diagnostic and research purposes in the 1970s and 80s and only later co-opted for treatment. Because much of the cortex is close to the skull, neuroscience researchers can more easily stimulate it than deeper structures like the internal capsule. For motor functions researchers can stimulate the motor cortex and measure the speed of conductance. Initially stuff like this was done by directly electrifying the scalp between two electrodes. A large enough current was needed to penetrate the skull and electrify the underlying cortex, but not so much that it caused a seizure. You can imagine how uncomfortable patients must have been as unruly electricity wreaked havoc on their scalp. By using a magnetic field to induce the cortex to fire instead of electrifying the scalp, patients could be more comfortable, and presumably the site of stimulation could be much better controlled.
I am going to ask you to reach back to your electrical physics knowledge and remember that passing current through a conductor can create a magnetic field and passing a conductor through a magnetic field can induce a current. Mechanical generators like wind turbines work this way by rotating a magnet field near a conductor. Current is electrons moving through a conductor, and current always creates a magnetic field. Magnetic fields however don’t always induce current. If the magnetic field is just hanging out, constantly reaching out its invisible tendrils into a conductor without changing, electrons don’t get very excited. Instead of flowing in a current, they’ll just line up like kindergarteners waiting for lunch: still wiggly, but not getting anywhere. You either have to make the magnetic field dance or make the conductor dance parallel to the magnetic field in order to get electronic juices flowing.
So, to extrapolate to pulsating brain tissue, if you pass a strong enough magnetic field through a certain region of the brain, and then make that field dance, you can create exogenous electrical activity. We need to modulate the magnetic field and not the head because, well, just imagine how many patients would want to be placed near a magnet and have their head vibrate for 30 minutes. Also, moving the head would change the location of the magnetic field, changing the part of the brain stimulated. Instead, TMS induces current in the head not by passing the head through the magnetic field, but by changing the magnetic field in a constant region of the brain. By doing this Magnetic Mamba through brain tissues, we can either stimulate or inhibit various brain regions.
Magnetic fields exponentially lose strength the farther they are from the source, so it takes a lot of energy to induce one that can effectively reach to the cortex from outside the head. You need a capacitor that can charge thousands of joules and discharge something like 500J of energy quickly through a coil, on and off over microseconds. I’m not even sure what that means, but I’ve read you also need the help of thyristor, whatever that is, to handle the current. It is much more intensive to make a field that can reach all the way into subcortical regions. It is beyond the scope of this discussion to get to deep into the details, but I hope that you have have enough information now to see that all those magnetic hats, doo-kickeys, and do-it-yourself TMS machines you see advertised on Facebook are likely not doing much more than wasting money or energy.
When I say TMS in reference to treatment of a patient, what I am actually referring to is rTMS or repetitive TMS. Instead of just one-and-done pulsing, patients who use TMS for depression, for example, may have repeated stimulations over the course of about half and hour (or less in some current methods I’ll discuss later). This repetition is what results in benefits and these benefits are presumably the result of changes in a person’s brain.
It's important to note that the developers and users of TMS grew up consuming a different ethical and legal soup than the developers of ECT. TMS was much more thoroughly researched for safety before it was widely used on patients. Unlike ECT, TMS developers didn’t find a stray human at the train station and hook him up to see what happened. There were protocols and oversight, informed consent and precedents. Plus, as opposed to the 1920s and 30s, in the 1970s and 80s there already existed some effective treatments for severely mentally ill patients, so the urgency to develop something, anything that worked was not as great. Instead, TMS was developed with substantially more foresight.
The first TMS machine approved by the US FDA during 2008 to 2009 was from a company called Neuronetics. Their machine was called the NeuroStar. The approval FDA gave the NeuroStar was very limited due to the limited data available in sponsored research. Only a highly specific protocol was approved and only for patients who had tried one, but not more than one, adequate antidepressant trial and failed to improve. Hopefully in future episodes I’ll have time to discuss their research, but suffice it to say for now that statistically significant improvement was found only in some secondary outcomes for depression. Even so limited, this approval was encouraging to the field because due process of research had produced a device and more generally a method of treatment that was unique and found to be safe through a more ethical process that ECT was initially subjected to. Now the door was open for more exploration that had the promise of actually making it into clinical use.
Additional devices have been approved with techno-babblish sounding names like the Brainsway Deep, the MagVita, the MagVenture, the NeuroSoft, the Cerena, and the Rapid Therapy Systems. Specific devices and protocols have been approved by the FDA for the treatment of major depressive disorder, acute migraines, and obsessive compulsive disorder. Location matters and coil designs and protocols need to be adjusted based on location. For OCD the FDA has approved a protocol applied bilaterally over the left and right DMPFC. Treatment for depression is focussed over the left DLPFC. The Cerena, on the other hand, is a take-home device that may help reduce pain in migraine by diffusely stimulating the occipital cortex.
Also, as I briefly mentioned earlier TMS can either inhibit or stimulate brain activity. For example, the Cerena is supposed to inhibit activity and therefore reduce the intensity of a migraine. TMS for depression is intended to INCREASE activity in the DLPFC. It is far beyond the scope of this podcast to get into the nitty-gritty, but there are innumerable ways to design devices that could purportedly stimulate or inhibit various regions of the brain. It is important that each new device and new claim be tested for safety and efficacy. Because TMS is relatively safe and considered non-invasive it is being investigated in just about everything you could imagine, so I won’t go into that here.
Despite it’s safety, TMS is not without potentially harmful side effects or contraindications. One of the most worrisome side effects is seizure induction. For ECT, this is what is expected, and the concern for ECT is inducing status epilepticus. In TMS a convulsive seizure, even a short one, is not the desired outcome, unless you are conducting MST (or magnetic seizure therapy), which I won’t cover here. rTMS is conducted in an office setting or even in the comfort of a patient’s home, so there are no anesthesiologists with syringes and artificial airways standing at the head of the bed. The rate of seizure in TMS is hard to estimate, but one 2020 study reported 41 total seizures among who knows how many treatments (maybe millions), making the risk of seizure extremely low. It appears that seizures are also most likely in those with risk factors for seizures, so for a patient without a history or significant risk factor for seizure, it is even more unlikely to happen.
Absolute contraindications for TMS are any number of implanted medical devices in the head, neck, or upper thorax. Some of this is more out of an abundance of caution and a deficit of data, but bad things can happen. The magnetic field generated by TMS can cause objects in which a current can be induced to heat up. Have you ever used an induction stovetop? You can cook a patient with TMS, so knowing the location and composition of a patient’s devices is crucial. There are some permanent cosmetics that might also have ferromagnetic particles that can conduct and potentially heat up or cause pain. TMS may also interfere with electrical and magnetic devices, and could de-program or inactivate them.
Talking about TMS can be confusing because there are a lot of ways to create magnetic fields and to fluctuate them. I have focused on rTMS which uses 10Hz pulses about 3000 times over the course of about a half and hour. I also also mentioned MST, which gives bursts that intentionally induce seizures. Now I want to mention another player in the magneto-sphere, which is iTBS (or intermittent theta burst stimulation). It is like rTMS, except patients get more energy. For example a protocol for iTBS might use 600 60Hz pulses/day over 3-4 minutes, while rTMS uses 3000 10Hz pulses per day stretched over a half hour. With iTBS you get higher energy dosing over less time, so you can say the energy density is higher. In 2018, the FDA recognized that iTBS is at least as effective as a comparable rTMS protocol and also takes less time, so they approved iTBS for treatment resistant depression.
The SAINT protocol I mentioned earlier accelerated the delivery of iTBS even faster, giving 18000 50Hz pulses per day. In addition, they used MRI mapping to target the left DLPFC more accurately. In the next episode, I will discuss the methods and results of the SAINT trial. If the findings of this trial stand up to the ruthless demands of scientific rigor, then iTBS may edge ECT out of the depression market-place, but it is still too early to tell.
In this episode, I discussed a brief history of TMS development, described in my pitiful way how TMS works, some of its indications and contraindications, and hopefully inspired you to want to find out what the next episode has in store.
Thank you for your time, and this has been an episode of PsyDactic - Residency Edition. 1–8