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Personalized TMS Treatments Might Be a Possibility for Patients with Treatment-Resistant Depression


When it comes to treating depression, there’s no singular method that’s universally effective. Unfortunately, for patients, this usually means a lot of trial and error with different types of antidepressants. Even so, as many as one-third of people do not respond to treatment for their depression—this is known as treatment-resistant depression. 

Transcranial magnetic stimulation (TMS) is a non-drug psychiatric treatment for depression that has been shown to help in cases where several types of antidepressants have failed. However, there’s no real way to know if TMS will work or not on someone, leaving doctors and patients wondering the same thing, “Why isn’t there an easier way to find an effective treatment for depression?” 

A recent study may have made progress in regard to this long-unanswered question. Keep reading to find out more about:

  • What treatment-resistant depression is, and what’s normally done to treat it
  • TMS, including what it is and how it works 
  • The study and its results

Treatment-Resistant Depression

What Is Treatment-Resistant Depression?

Treatment-resistant depression is depression that doesn’t improve or ceases to improve despite treatment. Like depression in all of its forms, treatment-resistant depression presents itself in many ways and varies from person to person. According to the FDA, depression can be considered treatment-resistant if the patient continues to feel depressed after having at least two adequate trials of antidepressants over a period of two years. 

Depressed girl cries in blue bathtub
Treatment-resistant depression is especially challenging to cope with because with every failed treatment comes increasingly intense feelings of hopelessness, which are already a predominant symptom of depression. 

Responding to Treatment-Resistant Depression

Antidepressants generally take four to six weeks to reach full effectiveness, which can feel like a lifetime to someone who’s just been diagnosed with depression. Furthermore, finding the right antidepressant isn’t always a simple process, and many patients struggle to determine what type of drug and/or combination of drugs is most effective for them. 

Aside from psychotherapy, which is usually the first treatment that patients will try, there are five main strategies for treating treatment-resistant depression:

  • Optimization — In order to ensure that an antidepressant is being fully optimized, a psychiatrist might suggest that a patient continue to take the same one for a longer period of time or to increase the dosage. 
  • Switching — Because there are several different classes of antidepressants, one class might work better than another for certain patients. A psychiatrist might switch to a new class of antidepressants if the first one does not work as expected.
  • Combination — If one antidepressant alone isn’t helping, a psychiatrist might combine different classes of antidepressants to see if a multi-tiered treatment is more effective. 
  • Augmentation — Augmenting a patient’s drug regimen with new drugs or increased dosages is another common route of experimentation. Augmentation might involve using medications that were developed for other purposes but have since shown to help treat depression. 
  • Somatic alternatives — A psychiatrist whose patient’s depression continues despite multiple treatment methods might suggest that the patient try a somatic, or non-drug, treatment as an alternative. Perhaps the best known somatic alternative is electroconvulsive therapy or ECT, which has become infamous due to historical misuse of the treatment and its negative portrayal in the media. However, ECT has undergone an evolution and is now considered to be a lot safer. A little lesser-known treatment that has been rising in popularity in recent years is TMS, which is regarded as being highly tolerable and, unlike ECT, is non-invasive. 

TMS: A Groundbreaking Means of Treating Depression

What Is TMS?

TMS uses magnetic pulses to stimulate the part of the brain where depression is thought to be most localized. The magnetic fields generated during TMS interact with electrical currents in the brain and over time can alter neurological chemistry, leading to improved mood and decreased symptoms of depression. As previously mentioned, TMS is non-invasive, which means it does not require patients to be sedated during treatment. Therefore, patients are fully conscious throughout TMS, and because the treatment does not affect cognition, patients can resume daily activities after a TMS session. 

Patient receiving TMS therapy with NeuroStar
TMS is extremely tolerable with little to no pain or discomfort. Some patients may get a headache during or after treatment, but it should not last long and can be treated with over-the-counter pain relievers. Image courtesy of Medscape

How Does TMS Work?

In order to create substantial changes in the brain, TMS must be consistently administered on a daily basis (five days a week) for around six weeks. While the length of each treatment session varies from patient to patient, the average time is around 30 minutes. During a TMS treatment, the patient is seated with an electromagnetic coil positioned against their head. As the pulses come through the coil, the TMS machine makes a clicking sound, and the patient will feel a light tapping sensation as the pulses are being transmitted. These pulses only affect the area directly beneath the electromagnetic coil, penetrating the skull to reach around 2 or 3 centimeters deep in the brain. 

Determining the Treatment Site

In order to find the right area of the brain (the prefrontal cortex) to target with each treatment, the TMS provider conducts a mapping session during which they attempt to stimulate the nearby motor cortex enough to trigger a physical reaction, usually the jerking of the patient’s fingers. If the patient does not feel the results from daily TMS sessions after around four weeks of treatment, the provider might remap the brain to try and locate a more precise area to stimulate. 

Diagram of TMS treatment location in the brain
TMS providers stimulate the motor strip because it elicits an immediate, external response from the patient, unlike stimulation of the prefrontal cortex, which causes gradual, internal changes to occur. Image courtesy of Manuel F. Casanova on ResearchGate

The Study: “Trajectories of Response to Dorsolateral Prefrontal rTMS in Major Depression”


Though TMS has proven to be effective for many patients with treatment-resistant depression, no previous scientific study had characterized the trajectories of patients’ responses to TMS. This absence of research prompted a team from the Centre for Addiction and Mental Health in Toronto to do some investigation into possible patterns that might become apparent following TMS treatments. 

The Results 

The subjects in the study were adults (ages 18 to 65) who had been diagnosed with major depressive disorder and had failed to respond to at least one trial with an antidepressant. The researchers saw four sub-groups emerge among the 388 participants throughout the study: 

  1. No response (11 percent of all participants)
  2. Rapid response to treatment (19 percent of all participants)
  3. A steady decline in participants with more severe symptoms (30 percent of all participants)
  4. A steady decline in participants with more mild symptoms (40 percent of all participants)

According to the researchers, the older patients were more likely to be rapid responders, the reasons for which they could not determine. Furthermore, these rapid responders were also more likely to have entered the study with more mild symptoms. Conversely, the non-responders were more likely to have entered the study with more severe symptoms. Additionally, the researchers found that benzodiazepines, which include tranquilizers like Valium and Lithium, seemed to interfere with the TMS’s effects. 

Following the study, the researchers concluded that “major depression shows distinct response trajectories to rTMS, which are associated with baseline clinical characteristics but not treatment protocol. These response trajectories with differential response to rTMS raise the possibility of developing individualized treatment protocols.” 

Hopefully, research focusing on personalizing TMS will continue to take place to increase the treatment’s accuracy as well as the rate at which patients experience relief from their symptoms. 

If You Have Treatment-Resistant Depression, TMS Might Be Right For You 

If you have tried one or more antidepressants but have not achieved remission for your depression, you may have treatment-resistant depression. TMS was approved by the FDA to treat major depressive disorder in 2008, and because it has gained so much traction in the psychiatric community, it is now covered by most insurance companies. This means that TMS is not only available for patients with depression, but it is also widely accessible for patients whose condition has proved to be treatment-resistant. 

Because TMS is non-pharmaceutical, most patients should be able to continue to take their antidepressants, allowing TMS to be incorporated rather seamlessly into a patient’s treatment regimen. Ask your doctor about finding a TMS provider near you, and jumpstart your journey toward a life without depression. 

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