TMS works better than antidepressants for many people with treatment-resistant depression. Clinical trials show higher success rates, faster symptom relief, and fewer side effects once multiple medications have failed. 

Antidepressants often lose impact after the second or third attempt. TMS presents a different method. Non-invasive, drug-free, and focused on stimulating underactive areas of the brain linked to mood. For patients stuck in the cycle of medication switches, this can be the turning point.

How Do TMS and Antidepressants Compare in Real Patients?

In clinical trials, TMS consistently outperforms antidepressants in treatment-resistant depression. The ASCERTAIN-TRD trial, a large, multi-center randomized study, directly compared rTMS to two standard medication strategies: switching to venlafaxine or duloxetine, or augmenting with aripiprazole.

Here’s what the numbers showed:

• Response rate for rTMS: 52.2%
• Response rate for antidepressant switching: 24.9%
• Response rate for aripiprazole augmentation: 25.3%

The difference wasn’t minor. On the Montgomery–Åsberg Depression Rating Scale (MADRS), rTMS led to an average symptom reduction of 17.39 points, compared to 13.22 points for those who switched medications. That 4-point gap reflects a clinically meaningful difference (1).

In another randomized study with 89 patients, rTMS patients had a remission rate of 27.1%, compared to just 4.9% in the group that changed medications. These patients had failed at least two previous antidepressant trials. In real-world terms, that’s a fivefold improvement in achieving full remission (2). 

Why Does Switching Antidepressants Often Fail?

Medication switching remains one of the most common responses to failed antidepressant treatments. But success rates drop significantly after the second failed attempt. According to the STAR*D trial, the probability of achieving remission after trying two antidepressants falls below 20%. Each failed trial adds more time, more side effects, and more discouragement.

Depression affects people in different ways. A medication that helps one person may do little or nothing for someone else due to:

• Genetic differences in how medications are metabolized
• Comorbid conditions like anxiety or chronic pain
• Underlying neurological patterns not addressed by SSRIs or SNRIs

Switching also resets the clock. Patients often wait 4 to 6 weeks to evaluate the new drug’s effect, enduring another round of side effects, weight gain, emotional numbness, insomnia, without knowing if relief will come. For many, this revolving door approach becomes exhausting.

How Does rTMS Offer an Advantage?

TMS works differently. Rather than altering brain chemistry systemically like medications do, rTMS uses magnetic pulses to stimulate the underactive brain regions involved in mood regulation. It targets the left dorsolateral prefrontal cortex, which tends to be underactive in people with depression.

This localized mechanism allows rTMS to:

• Activate neural circuits without affecting the entire body
• Avoid common drug side effects like sexual dysfunction or weight gain
• Deliver faster improvements, often within 2 to 3 weeks
• Achieve measurable results in patients who’ve failed multiple medications

Importantly, rTMS is non-invasive, requires no sedation, and has no recovery time. The most common side effect is a mild headache or scalp discomfort, usually resolving quickly.

It also improves more than just mood. rTMS outperformed antidepressants not only in treating depression but also in reducing anxiety and anhedonia. Two symptoms that are notoriously difficult to treat pharmacologically.

What About Augmenting With Aripiprazole?

Aripiprazole, an atypical antipsychotic, is frequently prescribed as an add-on treatment for depression. In the ASCERTAIN-TRD trial, it showed some benefit. While the response rate was lower than rTMS, patients reported a slightly better subjective experience than those who switched antidepressants. On a symptom questionnaire, aripiprazole showed a mean score change of −37.79, compared to −34.45 for switching.

However, aripiprazole is not without issues. It carries a risk of side effects including:

• Akathisia (restless legs, agitation)
• Weight gain
• Insomnia
• Emotional flattening
• Increased risk of suicidal thoughts in younger patients

Unlike rTMS, it alters brain chemistry across multiple pathways, which can make side effects harder to manage. And it often requires weeks of titration to reach a therapeutic dose.

For patients who have already endured multiple medication failures, the added risks and delayed relief make aripiprazole a less appealing choice, especially when rTMS delivers better clinical outcomes without the systemic burden.

Is TMS Also Effective for Depression With Anxiety?

In fact, TMS is one of the few depression treatments that also shows strong effects on anxiety. In a study of 1,820 patients with major depressive disorder, more than 75% also had clinical anxiety. Researchers tracked changes in both PHQ-9 (for depression) and GAD-7 (for anxiety) scores after TMS treatment (3).

Results:

• GAD-7 scores decreased markedly in the anxious depression group
• PHQ-9 scores improved significantly in both anxious and non-anxious groups
• Response rates ranged from 55.2% to 66.8%
• Remission rates ranged from 24% to 33.2%

These numbers matter. Patients with both anxiety and depression are less likely to respond to standard medications. They also experience more severe symptoms, worse functional impairment, and higher suicide risk.

TMS appears to close this treatment gap. It improves both mood and anxiety symptoms simultaneously, something many antidepressants fail to do. And unlike medications, it doesn’t rely on a slow titration period or systemic changes to brain chemistry. It works where the symptoms live, directly in the brain’s emotion regulation centers.

How Does TMS Fit Into a Broader Treatment Plan?

TMS is a strategic tool that fits into a broader, individualized treatment plan for depression. Most patients who undergo TMS have already tried at least two antidepressants without success. At that point, it becomes part of what’s called a multi-modal approach.

Here’s how TMS often works alongside other strategies:

• With medication: TMS can be used while continuing antidepressants. There’s no need to stop current prescriptions unless advised by a physician. It works differently and doesn’t interfere with drug action.
• With therapy: Cognitive behavioral therapy (CBT) or other talk therapies can continue during TMS treatment. In fact, some patients respond even better when combining the two.
• With lifestyle changes: Improving sleep, reducing alcohol use, exercise, and managing chronic stress can all enhance the effects of TMS.

Psychiatrists may also monitor for anxiety, insomnia, or trauma-related symptoms and treat them in parallel. TMS is most effective when depression is understood in the full context of a patient’s mental, emotional, and biological health. In high-functioning clinics, treatment planning is dynamic and ongoing. TMS is simply one of the most effective tools available when others have failed.

What Do Patients Experience During TMS?

TMS is an outpatient procedure. There is no anesthesia, no hospital stay, and no downtime. Each session lasts 3 to 20 minutes. Most patients come in five days a week over six to seven weeks, with occasional tapering afterward.

Here’s what a typical session looks like:

• The patient sits comfortably in a reclining chair.
• A small electromagnetic coil is positioned on the scalp.
• The technician calibrates the coil based on motor threshold mapping to target the specific brain area (usually the left dorsolateral prefrontal cortex).
• Rapid magnetic pulses are delivered in sequences lasting seconds at a time, followed by brief rest intervals.

What does it feel like? Patients usually report a tapping sensation on the scalp. Some feel mild discomfort or tightness during the first few sessions. Most adjust quickly. Mild headaches or scalp sensitivity may occur but typically fade within a day. Serious side effects are rare. Seizure risk is extremely low, far below 1% and mostly relevant only in those with a seizure disorder.

After treatment, patients can drive home, return to work, or resume daily activities. No recovery period is needed. The process becomes routine within the first week.

How Long Do TMS Effects Last?

For many patients, relief lasts for months, sometimes even longer. In real-world terms, that means:

• Some patients experience full remission and don’t need additional sessions for a year or more.
• Others return for booster treatments or preservation therapy every few months to maintain results.
• Maintenance plans are adjusted based on symptom patterns, relapse history, and individual needs.

Antidepressants must be taken daily and often come with long-term side effect risks. TMS, by contrast, offers periodic, targeted treatment without affecting the whole body. It works well for managing depression over time.

Looking for an Effective, Drug-Free Option?

Many people reach a point where antidepressants just don’t deliver. Side effects pile up, progress stalls, and relief stays out of reach. That doesn’t mean you’re out of options.

TMS Institute of Arizona helps patients who’ve already tried multiple treatments and still feel stuck. We use rTMS, which is backed by clinical data and delivered with precision. Each treatment targets the brain circuits involved in depression without medication, sedation, or downtime.

Patients come to us after years of trial and error. They stay because they start to feel clear again, sharper, and more themselves. Our team handles everything from evaluation to treatment right here in our Scottsdale, Arizona office. Thousands have gone through rTMS with us and finally felt real change. You can too. Contact TMS Institute of Arizona to get started.

References

1. Papakostas, G. I., Trivedi, M. H., Shelton, R. C., Iosifescu, D. V., Thase, M. E., Jha, M. K., Mathew, S. J., DeBattista, C., Dokucu, M. E., Brawman-Mintzer, O., Currier, G. W., McCall, W. V., Mandana Modirrousta, Macaluso, M., Bystritsky, A., Rodriguez, F. V., Nelson, E. B., Yeung, A. S., Feeney, A., & MacGregor, L. C. (2024). Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial. Molecular Psychiatry, 29(8), 2287–2295. https://doi.org/10.1038/s41380-024-02468-x
2. Dalhuisen, I., Oostrom, I. van, Spijker, J., Wijnen, B., Exel, E. van, Mierlo, H. van, Dieuwertje de Waardt, Arns, M., Tendolkar, I., & Eijndhoven, P. van. (2024). rTMS as a Next Step in Antidepressant Nonresponders: A Randomized Comparison With Current Antidepressant Treatment Approaches. American Journal of Psychiatry, 181(9), 806–814. https://doi.org/10.1176/appi.ajp.20230556
3. Carpenter, L. L. (2023, January 11). The Anxiolytic and Antidepressant Effects of Transcranial Magnetic Stimulation in Patients With Anxious Depression. Psychiatrist.com; The Journal of Clinical Psychiatry. https://www.psychiatrist.com/jcp/anxiolytic-antidepressant-effects-transcranial-magnetic-stimulation-patients-anxious-depression/