Magnetic Fields, Magic and Mental Health

The Clinical TMS Society Annual Meeting in Review

Greetings from the Frontier! Today we are focusing on the frontiers of brain stimulation in psychiatry. Last weekend we attended the Clinical TMS Society’s 9th Annual meeting and would love to share the highlights here. Recognizing that not everyone is interested in Transcranial Magnetic Stimulation, we will frame this around quotations that should resonate with most curious humans and try not to “talk shop” too much. 

For a quick Primer on TMS for those new to the mental health magic of magnets, we made this video awhile back:

“Diseases desperate grown, By desperate appliance are relieved, Or not at all.”- William Shakespeare in Hamlet

One of the most fascinating talks at the conference was delivered by Dr. Harold Sackeim, often called “the most biological psychiatrist in America” (though he is a psychologist) and the founding editor of Brain Stimulation. He was tasked essentially with predicting the future of brain stimulation and rarely is our mind blown, dear readers, but here we are. 

He highlighted the truly wild study results of a 2017 study on “social dominance” that used optogenetics to turn  “loser” mice into “winners.” Sure it is just mice but the implications here for cosmetic brain stimulation are profound. Imagine being able to stimulate your brain to have “learned resilience”, aka grit? Venture Capitalists and Angel investors emphasize they are often investing in the founders and looking for a certain type of magic. The idea that we could manipulate the dial on grit is both frightening and exhilarating. 

While the above is still quite a ways away from prime time for humans, Dr.Sackeim was pretty confident that within a few years many of us psychiatrists in the room would be directly administering drugs locally in the brain. He walked us through a company called Cerebral Therapeutics, which was founded by a neurosurgeon who could no longer practice his craft due to worsening eye sight. Cerebral Therapeutics is pioneering intracerebroventricular drug delivery. They have studies underway showing a 77%  reduction in seizure frequency targeting the hippocampus with Divalproex Acid  in patients with temporal lobe epilepsy. He imagined a world in which psychiatrists directly administered clozaril to the brain in people with schizophrenia.  Clozaril can have some life threatening systemic side effects limiting its more widespread use despite its efficacy. Keep an eye on this company to see if his predictions come true!

He also touched upon a wide array of neuromodulation devices in use now that are worth checking out: 

• The Vagal Nerve Stimulator for treatment resistant depression only works for a minority of people but for those it does, the results can be dramatic and durable. Trials underway with VNS need to be several years long because results take time to accrue. I recall many years ago working as research assistant on a trial of VNS for depression in kids getting it for seizures so it was interesting to get an update. 

• Relivion: a non-invasive multi-channel brain neuromodulation system that stimulates six branches of the occipital and trigeminal nerves for migraine headaches. There is also a version for depression that is under investigation

• Reliefband: a non-invasive, FDA cleared class II neuromodulation device for the treatment of nausea and vomiting associated with motion sickness, anxiety, physician-diagnosed migraines, hangovers, morning sickness, chemotherapy, and post-operative nausea and vomiting . It stimulates the median nerve which sends pulses to the Dorsal vagal complex, an area of the brain that controls nausea and vomiting. (A word of caution- if you look this up be prepared for an onslaught of targeted social media ads about carsickness)

And now, on to the star of the show, TMS.  

“It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so.”- Josh Billings (sometimes incorrectly and ironically misattributed to Mark Twain)

Having been to this annual meeting for several years, it is clear there are some ongoing areas of debate amongst TMS clinicians and one of them is whether or not bilateral or unilateral TMS is best for depression. Many assume that treating two sides would be inherently better than just treating the left side whereas others believe adding the right side is a waste of time. In the field of psychiatry, it is pretty rare to have data registries to answer empirical questions but thankfully, the folks at Neurostar have a large outcomes registry to do just that. Surprisingly, their dive into the data suggests that not only does bilateral TMS not appear to be superior, it may even be a little worse than unilateral. The thinking of “well it couldn’t hurt to add the right side protocol” may lead to worse outcomes after all. There may be certain situations where it makes sense but a one-size-fits all approach seems misguided. Without registries like these, we rely on sometimes false assumptions.

At our practice, we contribute anonymous outcome data on our TMS treatments to Brainsway, the makers of the devices we use, and believe these outcome registries are key to answering so many questions about best practices. As more and more psychiatrists start to incorporate interventional procedures like TMS and psychedelic medicine like Esketamine into their repertoire, device manufacturer registries and forward thinking mental health electronic medical record startups need to be on our radar. Two startups in this space I follow are Osmind and Maya Health and both track outcomes and allow patients and clinicians to participate in formal clinical trials. Recently, I joined Osmind’s Clinical Advisory Board alongside leaders in the field like Robin Carhart-Harris who led the recent groundbreaking study on psilocybin for depression. There is great excitement about machine learning in all of medicine and we need datasets for that. 

“The plural of anecdote is data”- Raymond Wolfinger

At an even more basic level, we need to share our experiences beyond single anecdotal case reports. That’s why I was excited to see that CTMSS’s TMS and Data Collection Affinity Group have launched a TMS Perinatal Registry. At our practice, we have a Perinatal Team led by Dr.Amanda Tinkelman and they are passionate about finding evidence-based approaches to treating Perinatal Mood an Anxiety Disorders. Given the favorable side effect profile of TMS and concern around the systemic impact of some psychiatric medications, it offers great promise for this population. However, we need to work together as a field to determine where it fits in the perinatal psychiatrist’s toolkit. In addition to the launch of the registry, there was also an interesting poster presented on the use of TMS in pregnancy suggesting in a small case series of 4 pregnant women, the standard protocol we use for depression was safe, well tolerated and effective.

“Medicine is a science of uncertainty and an art of probability” - Sir William Osler

Keeping with the theme of not assuming things that ostensibly make sense but turn out not be true, Dr.Aron Tendler, the medical director of Brainsway did something we rarely see at academic conferences: He shared the results of a failed trial! We learned more from this failure than any other talk in recent memory and so we would encourage conference organizers and journal editors to follow suit in publishing negative results. Dr.Tendler shared that in their study of deep TMS for PTSD, both the sham (aka placebo) group and the active treatment group got better but the sham group beat the active treatment! Participants in both groups used Script Driven Imagery (SDI) about their trauma, a type of exposure therapy for PTSD. It seems that the deep TMS protocol used, which targeted the medial prefrontal cortex interfered with this exposure work. In imaging studies of individuals with PTSD, there is often low activity in the prefrontal cortex and higher than normal activity in the amygdala, the brain’s fear processing center. Therapies for PTSD, such as EMDR (Prince Harry’s treatment of choice), Cognitive Processing Therapy and SDI promote activity in the prefrontal cortex.  It is possible that a different protocol could work for PTSD in conjunction with SDI, such as a protocol targeting the dorsolateral prefrontal cortex, could have more promising results but further research is clearly needed.

“Any sufficiently advanced technology is indistinguishable from magic”- Arthur C. Clarke

And finally, one of our favorite leaders in the neurostimulation field, Dr.Nolan Williams from Stanford, gave attendees a crash course on his accelerated TMS protocol for depression, known as the SAINT protocol. Instead of the standard 1 treatment a day for 36 treatments, SAINT is 10 treatments per day for 5 days. So far, three studies of it have suggested it leads to dramatic improvements in depression and suicidal thinking in under a week. His studies focus on individuals with what he terms “Surgical Level Depression”- people whose depression has not responded to interventions like ECT, countless medication trials and traditional TMS. How durable these results are remains an open question. At our practice, we do a modified version of this protocol which does not involve neuronavigation and have a robust data set ourselves we just need to write up (hint hint, any budding research assistants out there? Get in touch!). Dr.Muir wrote extensively about accelerated TMS in our practice’s blog and people travel from all over the world to places like Stanford and our practice in NYC to try it out when more traditional interventions for mood disorders fall short.

Stay Tuned….Stay Curious

There was a lot more and paid subscribers will have access to some audio excerpts from our recent pop-up Clubhouse room were we discussed the conference and took general audience questions about TMS. Look out for that post soon as well as others about mental health, social audio (including some technical audio guides thanks to Owen) and more.

Our weekly Clubhouse Creator First show, The Frontier Psychiatrists, will have its second episode this Friday at 1pm EDT (our “new normal” timeslot) so tune in for that and subscribe to our gCal that tracks all our upcoming appearances and Sphere Club happenings across social audio platforms! Tonight at 6:55 pm EDT we will be talking about psychiatric hospitalizations on AMA Frontier Psychiatrists, our weekly show featuring a panel of mental health experts with the Human Behaviour Club, the first club on the platform to hit half a million followers. We have psychiatrists who have worked at psychiatric hospitals, who have been patients on them and who have worked hard to keep people out of them so this should be a rich discussion.