From Heretical Idea to Mainstream Psychiatry: Brain Stimulation Has Ridden a Wave

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Back to table of contents Previous article Next article Clinical & ResearchFull AccessFrom Heretical Idea to Mainstream Psychiatry: Brain Stimulation Has Ridden a WaveMark George, M.D.Mark GeorgeSearch for more papers by this author, M.D.Published Online:15 Oct 2021https://doi.org/10.1176/appi.pn.2021.11.26AbstractBrain stimulation methods have progressed from unusual novelties and way-out ideas to sophisticated treatments that are now saving lives daily.I live a stone’s throw from the beach near Charleston, S.C., where I sometimes enjoy surfing. In the surf, I sit on my board and watch the incoming waves, selecting the one that seems best, paddling to it, and then timing my board with the wave. Once you’re up, it’s a rush, and you stay up as long as the wave allows and enjoy the ride.They call this feeling “pura vida”—joyful being and gratitude. My career in brain imaging and then brain stimulation has been like riding a most remarkable wave.Brain imaging techniques and analysis methods have transformed our ability to understand and image the brain. I remember the day during my residency when the first MRI scanner arrived. Disappointingly, a patient with a dense hemiparalysis had a “normal” MRI scan. We had a lot more to learn. (Acute ischemic strokes were not detectable with MRI.) Now we have robotic MRIs with the ability to image structure or function as well as compare a single patient’s results with thousands of other scans in the human connectome. We can map exactly what parts of the brain are involved in most activities and which cortical regions control deeper structures. PET, SPECT, and advanced EEG can reveal amazing information about our patients.Amazing as the brain imaging advances have been, the brain stimulation methods are the most thrilling developments of my career. Brain stimulation methods have progressed from unusual novelties and way-out ideas to sophisticated treatments that are now saving lives daily. The graph below shows the number of publications a year that mention “brain stimulation.” Starting with almost nothing in the year I was born—1958—about 7,000 publications a year now have the keywords “brain stimulation.” More important than publications, almost every other month now the FDA approves yet another brain stimulation method for treating a severe brain disorder.Although I and several others somehow knew that focally stimulating the brain would benefit psychiatric patients, we were a small minority. And the ideas that are now mainstream were largely considered heretical. Psychiatry had long-established traditions of talking therapies and psychopharmacology, but brain surgery and stimulation had a checkered past. Electroconvulsive therapy was and still is a life saver, but we had not yet invented the modern modifications that reduce its cognitive and other side effects.Refining Transcranial Magnetic StimulationI was extremely fortunate to see one of the first transcranial magnetic stimulation (TMS) machines being used for research when I was at Queen Square Hospital in London during my first imaging fellowship. I then was able to carry out important discovery studies at my next fellowship at the National Institutes of Health (NIH) in Bethesda, Md. Over many years, we refined TMS methods and then launched a positive industry trial, and the NIH sponsored the OPT-TMS study. The FDA cleared TMS in 2008, and developments have snowballed since then. There are now at least seven TMS devices that are FDA cleared for treating depression and likely over 40 TMS manufacturers on the planet. My friend and colleague Harold Sackeim, Ph.D., recently published a landmark post-registry study of real-world outcomes of patients with treatment-resistant depression who have received TMS in the years following FDA approval. Roughly 30% of patients who have tried and failed medications reach remission, and another 30% have their symptoms at least cut in half. TMS is also FDA cleared for obsessive-compulsive disorder (OCD), anxious depression, and smoking cessation. Exciting research is refining where to place the coil on each individual based either on imaging studies, biomarkers like heart rate changes, depression symptoms, or some combination. Other researchers are reducing six weeks of therapy to a single week. We’ve even done TMS in zero-G, preparing for TMS and other forms of brain stimulation on interplanetary missions.The excited surfer in me shouts, “Cowabunga!” What a wave!Another interesting aspect of brain stimulation methods is that they are not competitive with pharmacology or talking therapy. Brain stimulation brings together psychiatry’s different treatment traditions. In fact, brain stimulation methods are much more powerful when they are combined with integrated forms of therapy. The recent TMS approvals for smoking and OCD require that patients be anxiety provoked or craving during stimulation. And some medications boost the plasticity of TMS, pointing the way toward future combinational pharmacology.There is equally exciting research with other forms of brain stimulation, including cervical or transauricular vagus nerve stimulation (VNS); transcranial direct or alternating current stimulation (tDCS or tACS); and the newest method, pulsed ultrasound. The technologies are amazing, with closed-loop sensing devices and other Star Wars–like advances. However, the limiting factor for their use is that psychiatry does not have enough trained translational clinical researchers who can help move these wonderful ideas from the shelf to the patient’s bedside.Future Lies in Better Access, Less Expensive TechnologyAlthough the growth and flourishing of brain stimulation methods has been a marvelous story, rates of depression, addiction, and suicide continue to climb. These brain stimulation methods have not yet made a significant dent in terms of large-scale mental health. Some of this may be in part due to lack of knowledge. Sadly, in the United States, likely less than 5% of depressed patients who meet criteria for treatment with TMS actually receive treatment. Another factor in addition to lack of education may be the relatively high cost and inefficiency of how we use these technologies.Can we develop less expensive forms of brain stimulation that might be used at home? Transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, and other technologies are being tested now for home use. If they work, they may begin to make a larger impact, particularly during and after the COVID-19 pandemic, when patients are looking for home-based treatments.Luckily, I’m still on my brain stimulation surfboard. This amazing wave of brain stimulation methods continues to swell and grow. Brain stimulation methods are helping psychiatrists to treat our patients, decrease patients’ distress, battle stigma, and discover how the brain works in health and disease. What a wonderful ride it has been and will continue to be. ■“Differences in Antipsychotic Treatment Discontinuation Among Veterans With Schizophrenia in the U.S. Department of Veterans Affairs” is posted here.The 2017 analysis, “Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia” is posted here.Mark George, M.D., is a Distinguished University Professor of Psychiatry, Neurology, and Radiology and holds the Layton McCurdy Endowed Chair at the Medical University of South Carolina. He is also a staff psychiatrist at the Ralph H. Johnson VA Medical Center in Charleston and oversees the TMS clinic there. He is the editor-in-chief of the journal Brain Stimulation: Basic, Translation and Clinical Research in Neuromodulation. ISSUES NewArchived