Dmitry M. Arbuck, MD President and Medical Director Indiana Polyclinic Carmel, Indiana
Ali A. Farooqui, MD Integrative Psychiatry, PLLC Clinical Faculty Department of Psychiatry University of Louisville School of Medicine Louisville, Kentucky
Rif S. El-Mallakh, MD Professor and Director, Mood Disorders Research Program Department of Psychiatry and Behavioral Sciences University of Louisville School of Medicine Louisville, Kentucky
Disclosures Dr. Farooqui is a speaker for AbbVie and BioXcel. Dr. El-Mallakh is a speaker for Axsome, Idorsia, Intra-Cellular Therapies, Janssen, Lundbeck, Myriad, Noven, Otsuka, and Teva, and has received research support from Sunovion. Dr. El-Mallakh is Current Psychiatry’s Section Editor, Clinical Neuroscience. Dr. Arbuck reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers or competing products.
An unintended outcome of the increased interest in TMS has been an increased understanding of brain regions involved in psychiatric illness. TMS was able to bring knowledge of mental health from synapses to circuits.25 Work in this area has further stratified the circuits involved in the manifestation of symptom clusters in depression.26 The exact taxonomy of these brain circuits has not been fully realized, but the default mode, salience, attention, cognitive control, and other circuits have been shown to be involved in specific symptom presentations.26,27 These circuits can be hyperactive, hypoactive, hyperconnected, or hypoconnected, with the aberrancies compared to normal controls resulting in symptoms of psychiatric illness.28
This enhanced understanding of brain function has led to further research and development of protocols and subsequent FDA approval of TMS for OCD, anxious depression, and smoking cessation.29 In addition, it has allowed for a proliferation of off-label uses for TMS, including (but not limited to) tinnitus, pain, migraines, and various substance use disorders.30 TMS treatment for these conditions involves stimulation of specific anatomical brain regions that are thought to play a role in the pathology of the target disorder. For example, subthreshold stimulation of the motor cortex has shown some utility in managing symptoms of pain disorders and movement disorders,31,32 the ventromedial prefrontal cortex has been implicated in disorders in the OCD spectrum,33 stimulation of the frontal poles may help treat substance use disorders,34 and the auditory cortex has been a target for treating tinnitus and auditory hallucinations.35
The location of stimulation for treating depression has evolved. The Talairach-Tournoux coordinate system has been used to determine the location of the dorsolateral prefrontal cortex (DLPFC) in relation to the motor cortex. This was measured to be 5 cm from the motor hotspot and subsequently became “the 5.5 cm rule,” taking skull convexity into account. The treatment paradigm for the Hesed coil also uses a measurement from the motor hotspot. Another commonly used methodology for coil placement involves using the 10 to 20 EEG coordinate system to individualize scalp landmarks. In this method, the F3 location corresponds most accurately to the DLPFC target. More recently, using fMRI-guided navigation for coil placement has been shown to lead to a significant reduction in depressive symptoms.36
For depression, the initial recommended course of treatment is 6 weeks, but most improvement is seen in the first 2 to 3 weeks.14 Therefore, many clinicians administer an initial course of 3 weeks unless the response is inadequate, in which case a 6-week course is administered. Many patients require ongoing maintenance treatment, which can be weekly or monthly based on response.37
Research to determine the optimal TMS dose for treating neuropsychiatric symptoms is ongoing. Location, intensity of stimulation, and pulse are the components of stimulation. The pulse can be subdivided into frequency, pattern (single pulse, standard, burst), train (numbers of pulse groups), interval between trains, and total number of pulses per session. The Clinical TMS Society has published TMS protocols.38 The standard intensity of stimulation is 120% of the motor threshold (MT), which is defined as the amount of stimulation over the motor cortex required to produce movement in the extensor hallucis longus. Although treatment for depression traditionally utilizes rapid TMS (3,000 pulses delivered per session at a frequency of 10 Hz in 4-second trains), in controlled studies, accelerated protocols such as intermittent theta burst stimulation (iTBS; standard stimulation parameters: triplet 50 Hz bursts at 5 Hz, with an interval of 8 seconds for 600 pulses per session) have shown noninferiority.36,39
Recent research has explored fMRI-guided iTBS in an even more accelerated format. The Stanford Neuromodulation Therapy trial involved 1,800 pulses per session for 10 sessions a day for 5 days at 90% MT.36 This treatment paradigm was shown to be more effective than standard protocols and was FDA-approved in 2022. Although this specific iTBS protocol exhibited encouraging results, the need for fMRI for adequate delivery might limit its use.
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