The last few months have seen major advancements of TMS in the treatment of psychiatric illness. In August TMS was approved by the FDA for the treatment of Obsessive-Compulsive Disorder, a third indication after depression in 2008 and migraine with aura in 2013 (this approval was broadened in September 2017 to include prevention of migraine). The FDA’s announcement included the following statement by Carlos Peña, PhD, MS, and director of the Division of Neurological and Physical Medicine Devices in the FDA’s Center for Devices and Radiological Health, “Transcranial magnetic stimulation has shown its potential to help patients suffering from depression and headaches; with today’s marketing authorization, patients with OCD who have not responded to traditional treatments now have another option.” The specific device approved is Brainsway’s H7 coil which targets the medial prefrontal and anterior cingulate cortices. The treatment takes 30 minutes and is administered five times a week for 6 weeks. One month follow-up outcomes showed significant benefit in active vs sham subjects. Because of Brainsway’s unique H-coil design, it may be some time before other FDA-approved TMS devices utilizing the traditional figure-8 coil receive approval for OCD.
August also saw the FDA’s approval of a newer, much quicker TMS treatment for depression. Whereas traditional TMS depression treatments have relied on a 10-20Hz protocol taking anywhere from 18-40 minutes to administer, the new protocol utilizes a different pattern of TMS known as Theta Burst Stimulation (TBS). TBS protocols take as little as three minutes to administer and have been known in research circles for years as a faster and equally effective method of administering TMS. Currently, the only device to have received this approval is Magventure’s MagVita TMS Therapy system, though as the Magventure system employs the traditional figure-8 coil, it will likely not be long before other manufactures receive this approval as well. Whether or not the faster TMS treatment will have an impact on insurance reimbursement remains to be seen – a treatment that used to take half an hour now takes three minutes, with some speculating insurers will mandate patients first fail treatment with TBS to then receive other TMS protocols.
There are numerous studies continuously being published that add to the growing body of literature supporting TMS as an effective treatment for psychiatric and neurological conditions, including just recently Tobacco Use Disorder, Parkinson’s, Somatic Symptom Disorder, and stroke. But one study published this summer in JAMA Psychiatry has received a lot of attention for being one of the few TMS studies that did not find a difference between active and sham treatment groups. The study, ‘Effect of Repetitive Transcranial Magnetic Stimulation on Treatment-Resistant Major Depression in US Veterans; A Randomized Clinical Trial,’ was an effectiveness trial and not an efficacy trial – participants with PTSD, previous Substance Abuse, and multiple medical comorbidities were allowed to participate as long as when asked by screeners reported depression as being their primary psychiatric problem as opposed to any other psychiatric condition. There was a mathematical difference of outcome in participants who had MDD without PTSD, which would have reached significance if this study was able to double the number of participants thus increasing its power. What might be more interesting though than how effective the treatment was for the active treatment group – 41% of active treatment participants achieved remission, is that the sham treatment group also reported such a high remission rate, 37%. Compare this to the 5% sham remission rate in the OPT-TMS trial (the study that lead to FDA approval of TMS for depression) as well as the 7% sham remission rate in the Neuronetics manufacturer’s trial, and one must wonder what is behind this discrepancy.
This is not the first time a randomized clinical trial involving military veterans with psychiatric disorders in the VA system has failed to show efficacy for a treatment that had been effective in initial studies. Earlier this year, a VA study found no difference between Prazosin and placebo in the treatment of PTSD-associated nightmares. There was a negative randomized trial of sertraline for PTSD, despite the FDA’s approval of the drug for this condition. Other examples include a negative trial of trauma-focused psychotherapy for PTSD, a negative trial of FDA-approved naltrexone for alcoholism, and a negative trial of depot risperidone (vs. oral) for schizophrenia – all in solely VA populations. Why is the veteran population so often at odds with the general population? One proposed reason lies in who these people are and the training they received. All of these study participants go through at a minimum basic training i.e. boot camp where the purveying ethos is no man left behind; these are people willing to take a bullet for one another. Devotion to the cause, ‘esprit de corps,’ is impressed heavily among veterans and lasts a lifetime. Though a veteran themselves may not be experiencing benefit of a particular treatment or therapy, they may be inclined to see that one of their combat brethren has the opportunity for wellness, and over-report improvement to make a particular therapy or medication available to all, not appreciating the impact this has on statistical analysis.
There are numerous proposed reasons studies of the VA population often do not coincide with studies of other populations, medication compliance, selection bias, and secondary-gain issues among them. The VA however, thankfully, is familiar with the shortcomings of studies performed in their facilities, and practitioners in this community continue to prescribe Prazosin for PTSD-associated nightmares, depot risperidone for Schizophrenia, and naltrexone for alcoholism. Recommendations in VA practice guidelines state that sertraline be used as first-line pharmacotherapy for PTSD, with trauma-focused psychotherapy promoted as first-line evidence-based psychotherapy. Finally, with the data from this recent TMS study in front of them, the VA purchased 40 TMS devices for use in its facilities around the country.
Indeed, these are exciting times in the field of TMS. This summer I had the pleasure of working with neuroscientists in the brain stimulation labs at the Medical University of South Carolina, where TMS took root more than two decades ago, and the most cutting-edge TMS and brain stimulation experiments are currently under way. TMS as an instrument to measure consciousness, EEG-guided TMS, TMS for pain, cocaine addiction, and acute suicidality, are not far-off theoretical concepts, rather their future applications are being tested right now, and show great promise for the treatment of many neuropsychiatric conditions.
Dr. Shapiro is currently a fourth-year psychiatry resident at Westchester Medical Center in Valhalla New York. adam-shapiro@hotmail.com.
