Transcranial magnetic stimulation (TMS) is a non-invasive treatment that uses magnetic fields to stimulate nerve cells in the brain, offering an alternative approach for certain neurological and psychiatric conditions. The technology has evolved from a research tool into a clinical therapy, with its adoption regulated by the U.S. Food and Drug Administration (FDA). This regulatory process has established specific milestones for its use, beginning with its initial application for major depression and subsequently broadening its scope. The historical timeline of these regulatory clearances provides insight into the increasing acceptance of this neuromodulation technique.
How Transcranial Magnetic Stimulation Works
TMS operates on the principles of electromagnetic induction to influence brain activity without the need for surgery. A device called a stimulator discharges a strong electrical current into a coil placed near the patient’s scalp, which generates a brief, focused magnetic field. This magnetic field easily passes through the skull and induces a secondary electrical current in the underlying brain tissue.
The induced electrical current causes the depolarization or hyperpolarization of neurons, thereby modulating their activity. By precisely controlling the magnetic pulse, clinicians can either increase or decrease the excitability of a targeted region, such as the left dorsolateral prefrontal cortex in depression treatment. Because the magnetic field generally penetrates only 2 to 4 centimeters below the surface, the treatment is typically focused on superficial brain areas.
When magnetic pulses are delivered individually or in pairs, the technique is simply known as single-pulse TMS, often used for research purposes to map brain function. However, when the pulses are delivered in rapid succession over a treatment session, it is referred to as repetitive TMS (rTMS). Repetitive protocols can be high-frequency, which tends to increase activity, or low-frequency, which tends to decrease activity, depending on the desired clinical outcome.
The Initial FDA Clearance for Major Depression
The landmark regulatory clearance that brought TMS into clinical practice in the United States occurred in 2008. The FDA granted this clearance specifically for the treatment of Major Depressive Disorder (MDD) in adult patients. This was a significant development, as the therapy was authorized for individuals who had not achieved satisfactory improvement from prior antidepressant medication.
The initial approval was based on data from a pivotal, multisite, randomized, sham-controlled clinical trial involving over 300 patients with treatment-resistant depression. This study demonstrated that active TMS treatment significantly outperformed the sham (placebo) treatment in improving depression symptoms, as measured by standardized scales like the Montgomery-Asberg Depression Rating Scale. The results showed that the therapy was both safe and efficacious for this specific patient population.
The first device to receive this clearance was the NeuroStar TMS Therapy System, developed by Neuronetics. This regulatory milestone was granted through the Premarket Approval (PMA) pathway, which is the most stringent type of device marketing application required by the FDA. The approved protocol targeted the left dorsolateral prefrontal cortex, a brain region consistently implicated in mood regulation and depression.
The clearance solidified TMS as a viable, non-pharmacological option for patients who could not tolerate or did not respond to traditional antidepressant medications. The initial protocol involved administering magnetic pulses five times a week for four to six weeks, with each session lasting approximately 37 minutes.
Timeline of Expanded Indications
Following the initial clearance for major depression, the FDA continued to evaluate and approve TMS technology for a wider range of conditions. The first non-psychiatric condition to receive clearance was migraine headaches with aura in 2013, when the eNeura Cerena System was cleared for the acute treatment of pain associated with these migraines. This clearance marked a significant expansion into the field of neurology.
The next major psychiatric condition to receive FDA clearance was Obsessive-Compulsive Disorder (OCD). In 2017, the BrainsWay Deep TMS System became the first to be cleared as an adjunct treatment for OCD in adults. This approval relied on a different coil technology designed to stimulate deeper and wider brain areas than the original depression protocols.
Further refinement led to the clearance of intermittent Theta Burst Stimulation (iTBS) protocols for MDD in 2018. The iTBS protocol delivers magnetic pulses in short bursts at a higher frequency, drastically reducing the treatment time for depression from nearly 40 minutes to about three minutes per session.
In 2020, the FDA expanded the use of deep TMS technology to include smoking cessation, establishing a new therapeutic application in addiction medicine.