Brain stimulation poised to move from last resort to frontline treatment

Imagine undergoing a medical experiment where the electrical circuits nearby occasionally explode with a blue flame. That’s how Mark S. George, a pioneer in transcranial magnetic stimulation (TMS), describes the early days of his research. It wasn’t exactly reassuring, but decades later, TMS has evolved into a safe and effective treatment for major depressive disorder—one that’s changing lives.

While the shape of the TMS coil and the target areas on the skull have changed somewhat in recent years, the basic approach remains roughly the same. Clinicians apply a painless magnetic pulse to the skull by means of a coil. The flux induces an electric field that modifies neuronal activity. Image credit: Shutterstock/Pepermpron.

A Revolution in Depression Treatment

Once dismissed as a fringe idea, TMS is now a mainstream therapy for adults with depression who don’t respond to medication. About two-thirds of these patients experience significant improvement, and thanks to brain imaging advancements, remission rates in clinical trials have soared to nearly 80%. Beyond depression, the therapy has also been approved for obsessive-compulsive disorder (OCD) and even smoking cessation.

Despite these successes, scientists believe that TMS and other noninvasive brain stimulation techniques—such as refined electroconvulsive therapy (ECT) and transcranial direct-current stimulation (tDCS)—are still in their early days. The key to unlocking their full potential lies in deeper understanding: how they interact with neural circuits and how they can be personalized for better outcomes. Some experts argue that with its safety and effectiveness, TMS should be a frontline treatment for depression rather than a last resort.

Shocking the Brain: A History

The idea of using electricity to alter brain function isn’t new. In the early 20th century, doctors found that inducing seizures through electrical stimulation could "reset" the brains of patients with severe mental illnesses. However, side effects like amnesia and the rise of antidepressants like Prozac pushed ECT to the sidelines.

The game changed in 1985 when Anthony Barker developed TMS, which used magnetic fields instead of direct electric shocks to stimulate the brain. Unlike ECT, it didn’t induce seizures, which led many to doubt whether it could be clinically effective. At the time, psychiatry largely viewed the brain as a "chemical soup," focusing on neurotransmitters like serotonin rather than brain circuits. But mounting evidence showed that TMS could influence deeper brain networks, sparking a shift in thinking.

Fine-Tuning the Pulse: The Rise of TMS

By the 1990s, scientists were experimenting with different coil shapes and pulse frequencies to improve TMS targeting. These innovations helped TMS secure FDA approval in 2008 for treating depression in patients who had failed at least one antidepressant.

The real breakthrough came when researchers discovered the importance of precision targeting. Originally, doctors placed the TMS coil using a simple rule: find the motor cortex (where moving the coil makes the thumb twitch), then shift forward a few centimeters. However, since brain anatomy varies from person to person, this approach led to inconsistent results. Enter neuro-navigation—using brain scans to precisely target the right circuits.

The Fast-Track to Remission

One of the biggest barriers to TMS adoption was the commitment: six weeks of daily hour-long sessions. Then, Stanford’s Nolan Williams had a revelation—why not intensify treatment for faster results? By tripling the pulse dose and condensing the therapy into just five days of short, high-frequency sessions, he developed Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT). The results were staggering: in a clinical trial, 11 out of 14 patients experienced remission within four weeks, compared to just two in the control group. Many patients felt better within just 2.6 days.

The FDA’s approval of SAINT in 2022 was a landmark moment. For the first time, neuroimaging was integrated into a psychiatric treatment, setting a precedent for personalized mental health care.

Beyond TMS: The Future of Brain Stimulation

TMS isn’t the only technique benefitting from these insights. ECT, long criticized for its side effects, is undergoing a quiet revolution, with modified protocols that reduce memory loss while maintaining effectiveness. Meanwhile, tDCS—a cheaper, simpler method involving low-intensity electrical currents—has shown promise for at-home depression treatment when combined with telehealth supervision.

Looking further ahead, transcranial ultrasound (TUS) could be the next frontier. Unlike TMS, which primarily affects surface-level brain areas, TUS can reach deeper structures, potentially revolutionizing treatment for conditions like chronic pain, dementia, and traumatic brain injury.

The Ultimate Goal: Precision Psychiatry

One of the biggest challenges in psychiatry is figuring out who will respond to what treatment. Right now, about 30% of people with depression don’t respond to conventional treatments—including TMS. But researchers are hunting for biomarkers—brain activity patterns, EEG readings, and even heart rate changes—that could predict a person’s response to treatment. Personalized brain stimulation, tailored to an individual’s unique neural patterns, could be the future of mental health care.

Surprisingly, adolescent brains seem resistant to TMS. While adult patients show significant benefits, a major 2020 study found that teenagers responded no better to TMS than to placebo treatment. Researchers suspect differences in brain development might require adjusted protocols for younger patients.

A Paradigm Shift in Mental Health

Brain stimulation is poised to become a standard part of mental health treatment. As technology advances, it may even be used preventatively, much like how lifestyle changes and medications manage heart disease. Instead of waiting until depression reaches a crisis point, patients could receive brain stimulation as early intervention.

With suicide rates remaining stubbornly high despite new antidepressants, the rapid relief that cutting-edge brain stimulation provides could be life-saving. As TMS pioneer Sarah Lisanby puts it, the field is on the verge of a transformation: “When you think about it, the way you really want to deal with depression is through prevention.”

If brain stimulation lives up to its promise, the future of psychiatry might look very different—and for millions of people, much brighter.

Citations: https://www.pnas.org/doi/10.1073/pnas.2401731121