TMS Therapy as a New Hope for Treatment-Resistant Depression

Depression becomes “treatment-resistant” when the usual therapies—talk therapy and standard antidepressants—don’t work. This often happens because multiple factors interact in ways that outlast simple fixes. For some, a family history of stubborn depression or early-onset episodes makes recovery harder. Others carry low-grade inflammation or hormonal imbalances that keep stress responses stuck in the “on” position. Difficult life experiences—like childhood trauma or ongoing financial and relationship pressures—can deepen the condition, while certain thinking styles (perfectionism, constant worry, negative loops) reinforce it. Finally, changes in brain circuitry and reduced flexibility to rewire itself might cause the usual pills to miss the mark. When these biological, psychological, and social factors overlap, more targeted treatments—beyond another medication trial—are needed.

A study called STAR*D tracked people who tried up to four different antidepressant pills one after the other. Here’s what they discovered:

• First try: About 4 in 10 people (37%) felt fully better.
• Second try: That dropped to just 3 in 10 (31%).
• Third try: Only 1 in 7 people (14%) reached full relief—and side effects became much tougher, so more than one-third (35%) gave up on the medication before it even had a chance to work.

Those results make it clear: simply swapping one antidepressant for another often leaves too many people still stuck in depression—and points to the need for treatments that work in entirely different ways.

Transcranial Magnetic Stimulation (TMS) is a non-invasive, FDA-approved procedure that uses gentle electromagnetic pulses to “wake up” underactive parts of the brain involved in mood (and even obsessive-compulsive) disorders. First cleared by the FDA in 2008, TMS has since shown high response and remission rates for people with treatment-resistant depression—67% respond (≥50% symptom improvement) and ~37% reach full remission.

LifeStance uses specialized TMS devices (i.e. Neurostar and Magstim chairs) for treatment, and each TMS session is closely monitored by a TMS technician.

What this means for you is that TMS offers a powerful, durable treatment for individuals whose depression has not improved with medication—highlighting its reputation for real-world efficiency and patient satisfaction.

A standard TMS course involves 36 sessions, delivered five days a week over six weeks. Each session lasts about 20–30 minutes, and because there’s no anesthesia or sedation, the individuals stay awake, feel what is typically described as a mild tapping sensation on their scalp, and can drive themselves home immediately afterward.

TMS therapy has relatively few known side effects, and most are mild and temporary. The most common side effects are mild headaches and scalp discomfort, often occurring at the treatment site. Other potential side effects include sleep changes and mild temporary facial pain. While seizures are a serious potential side effect, they are extremely rare, with a risk of less than 1 in 10,000.

• Electroconvulsive Therapy (ECT) is a long-standing treatment for severe, treatment-resistant depression in which a brief, controlled seizure is induced under general anesthesia. While ECT can be highly effective—especially for cases with psychotic features or life-threatening symptoms—it often causes short-term memory loss, requires recovery time, and carries the usual risks of anesthesia. Transcranial Magnetic Stimulation (TMS), by contrast, uses magnetic pulses to stimulate the same mood-regulating brain regions without inducing a seizure or needing anesthesia. Individuals remain fully awake, usually experience only mild scalp tenderness or a headache, and can return to their normal activities immediately—making TMS a far gentler, non-invasive alternative for those with treatment-resistant depression.
• Traditional antidepressants can lead to daily, whole-body effects such as nausea, fatigue, weight gain, sexual dysfunction, and sedation.
• Atypical antipsychotics, often added to an oral antidepressant for TRD, frequently carry risks of significant weight gain, metabolic syndrome, and even diabetes.

Because TMS targets only specific brain circuits without anesthesia or systemic drugs, it avoids these broader risks—allowing patients to resume normal activities immediately and making it far better tolerated than ECT or daily medications.

Before starting Transcranial Magnetic Stimulation, the person is screened for certain contraindications. You cannot receive TMS if you have any non-removable, magnetically sensitive metal objects in or around your head, including:

• Implanted electrodes or stimulators
• A deep brain stimulator
• Aneurysm clips or coils
• Cochlear implants
• Intracranial stents
• Bullets or other metal fragments
• Vagus nerve stimulators

Other medical concerns—such as seizures, significant head injuries, or unusual brain lesions—are also reviewed by the TMS psychiatrist during your evaluation to help ensure safety.

Looking ahead, Transcranial Magnetic Stimulation (TMS) has emerged as one of the most effective treatments for treatment-resistant depression we currently have, helping roughly 67% of people with TRD cut their symptoms by half and sending about 37% into full remission—all while typically causing only mild, temporary side effects like scalp tenderness and headache. TMS joins a family of neurostimulation approaches—such as Electroconvulsive Therapy (ECT), Deep Brain Stimulation (DBS), and Vagus Nerve Stimulation (VNS)—that directly target brain circuits when medications alone fall short.

Beyond stimulation, the novel nasal spray Spravato® (esketamine) often provides rapid relief by engaging different neurotransmitters. And on the horizon are promising pipeline therapies—Magnetic Seizure Therapy, Transcranial Direct Current Stimulation, intravenous ketamine, guided psychedelics, anti-inflammatory and immune-modulating agents, and neurosteroid treatments—that could further expand our toolkit for hard-to-treat depression.