Transcranial Magnetic Stimulation in Psychiatry: Historical Reflections and Future Directions

The history of transcranial magnetic stimulation (TMS) in psychiatry spans disciplines, continents, and decades, and it upended prevailing dogma. Initially developed as a tool to probe the motor system in neurology, TMS induces electricity in the brain without inducing a seizure (when given within safety limits). TMS made its debut in 1985 in the United Kingdom when the prevailing dogma in psychiatry was that a seizure is necessary for the therapeutic effects of electroconvulsive therapy (ECT). The idea of treating depression with electricity alone without inducing a seizure was viewed with skepticism. Fortunately, a group of pioneering researchers across several countries in the early 1990s saw TMS as a promising means of treating severe depression without the cognitive side effects of ECT. Borrowing methods used to study the motor system (a large round coil positioned on the vertex) and the fastest repetition rate available to them in 1993 (0.25–0.5 Hz), a team in Germany treated 2 patients with treatment-resistant depression, one of whom showed benefit ( 1 Höflich G. Kasper S. Hufnagel A. Ruhrmann S. Möller H.-J. Application of transcranial magnetic stimulation in treatment of drug-resistant major depression—A report of 2 cases. Hum Psychopharmacol. 1993; 8: 361-365 Crossref Scopus (223) Google Scholar ). In 1994, a group in Israel took a similar approach in 10 patients with depression and 10 patients with schizophrenia ( 2 Grisaru N. Yarovslavsky U. Abarbanel J. Lamberg T. Belmaker R.H. Transcranial magnetic stimulation in depression and schizophrenia. Eur Neuropsychopharmacol. 1994; 4: 287-288 Crossref Scopus (134) Google Scholar ). In 1995, a team from Germany and Austria reported significant antidepressant effects of this approach in a randomized controlled trial ( 3 Kolbinger H.M. Höflich G. Hufnagel A. Müller H.-J. Kasper S. Transcranial magnetic stimulation (TMS) in the treatment of major depression—A pilot study. Hum Psychopharmacol. 1995; 10: 305-310 Crossref Scopus (176) Google Scholar ). That same year, researchers in the United States took a different approach—informed by neuroimaging findings in depression, they used the more focal figure-8 coil to target the left dorsolateral prefrontal cortex using the higher repetition rate that was available then (20 Hz repetitive TMS) and reported significant antidepressant effects in an open-label trial ( 4 George M.S. Wassermann E.M. Williams W.A. Callahan A. Ketter T.A. Basser P. et al. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995; 6: 1853-1856 Crossref PubMed Scopus (792) Google Scholar ). In 1996, a team in Spain reported the first randomized controlled trial of repetitive TMS targeting the dorsolateral prefrontal cortex for depression ( 5 Pascual-Leone A. Rubio B. Pallardo F. Catala M.D. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996; 348: 233-237 Abstract Full Text Full Text PDF PubMed Scopus (1030) Google Scholar ). Numerous randomized controlled trials, meta-analyses, and an industry-sponsored pivotal trial later, the U.S. Food and Drug Administration cleared TMS for the treatment of depression in adults in 2008. Subsequent clearances followed, for presurgical mapping in 2009, migraine with aura in 2013, obsessive-compulsive disorder in 2019, smoking cessation in 2020, and comorbid anxiety in major depressive disorder in 2021. How did we get here, and what have we learned along the way? This commentary touches on a few lessons from the past that may be useful to reflect on as TMS reaches its fifteenth year after U.S. Food and Drug Administration clearance.