TMS Treatment for Depression

TMS, or transcranial magnetic stimulation, is a treatment for depression and other mental health disorders that has been shown to help patients who haven’t responded to therapy and medication. TMS works by using high-frequency magnetic pulses to stimulate a brain region that is underactive in people with depression.

The FDA approved TMS for use in adults with what’s called treatment-resistant depression in 2008. It hasn’t been approved for use in adolescents. But a substantial number of studies have shown TMS to be safe and effective for adolescents, and it is increasingly being used to treat adolescents off-label.

TMS is a non-invasive procedure that directs a series of electromagnetic pulses at a brain region called the DLPFC, or dorsolateral prefrontal cortex.

Lucian Manu, MD, the founding director of the Stony Brook Treatment Resistant Depression Program, is a psychiatrist with extensive experience using TMS to treat people, including adolescents, who haven’t responded to other treatments for depression. Dr. Manu explains the effect of TMS to patients and parents, by showing them a picture of a neuron connecting to other neurons. “When you image the brain of depressed patients, these neurons are atrophied. They’re shriveled. They’ve lost connections with other neurons. When a critical mass of connections is lost, that’s when people start having symptoms.” The TMS creates a weak electrical field around the brain cells in the target area, he adds, and that revitalizes them.

He compares underactive neurons to trees in winter that have lost their leaves. TMS reinvigorates those neurons, he explains, prompting them to create more active connections.

A patient treated with TMS sits in a chair with a cap or helmet fitted on their head that places the stimulator, containing a magnetic coil, close to their scalp. In a session that usually lasts from about 20 to more than 30 minutes, the patient receives hundreds of magnetic pulses targeted at the DLPFC. In standard treatment, these sessions are repeated 5 days a week for a total of 30 to 36 sessions over 6 or more weeks.

Magnetic imaging, such as an MRI or fMRI, is sometimes used at the start of TMS treatment to locate the target area.

The most widely used and extensively tested TMS technology in the US (brand name NeuroStar) uses a figure-8-shaped coil. But there is a newer technology called deep TMS (brand name BrainsWay), which uses an H-shaped coil. The H-shaped coil is said to reach a larger area, deeper in the brain than the figure-8-shaped coil, and it does not require imaging to target the correct area.

The machines that generate magnetic pulses for TMS make a lot of noise, so patients are advised to wear earplugs. Unlike electroconvulsive therapy (ECT), TMS doesn’t require sedation, so the patient can drive home after the treatment. The strength of the magnetic field is comparable to that of an MRI, and the TMS energy exposure is only half that delivered by ECT.

During TMS treatment, a patient taking antidepressant medication can continue it, although some choose to stop. “Sometimes patients don’t like taking medication, or their parents don’t like giving it to them,” Dr. Manu reports. “So if patients feel better with TMS, parents, in general, tend to want to take them off their medications, and I think that’s fine.” Dr. Manu encourages patients to continue in psychotherapy during TMS treatment.

It’s usually clear whether TMS is reducing a patient’s symptoms of depression by the midpoint of treatment — 15 to 18 sessions. If patients report improvement very quickly, it can be a kind of placebo response, Dr. Manu notes. “You want to make sure that the early response is real response, not a wannabe.”

How long the results will last is difficult to predict. “I’ve had patients who got better and stayed well for many months — over a year,” says Dr. Manu. “And I’ve had patients who relapsed weeks after they stopped the treatment. There’s just no way to foresee that.”

Some clinicians recommend that patients who have gotten good results from a course of treatment with TMS continue with a schedule of several “maintenance sessions” a month to forestall relapse.

What percentage of patients respond to TMS? “If you look at all the studies done with standard-protocol TMS, regardless of whether it’s deep TMS or conventional TMS, the take-home message is that about one third of people go into remission,” explains Dr. Manu, which means their symptoms are gone. “Then you have another third who go into what we call ‘full treatment response,’ which is at least 50 percent reduction in symptoms. Then you have about a third of people who don’t get either of those.”

Treatment of depression is the most thoroughly studied and widely adopted use of TMS. TMS is also FDA-approved for OCD and for quitting smoking. Some very small trials have shown promise for alleviating symptoms of autism.

For his patients with depression, after an initial evaluation, Dr. Manu offers them a choice of several treatments, including TMS, ketamine, ECT, and vagus nerve stimulation. He explains the pros and cons of each to give the patient — and in the case of adolescents, the parents — a good sense of how each option might affect them and how it would fit into their life.

Dr. Manu says it’s important to follow the patient’s lead. “What do they see themselves engaging with? What do they think appeals to them? Because it’s very important for patients to invest a lot of capital — a lot of faith, emotion, and hope that these treatments will work. It ensures that the patient will be diligent about treatment.”

This is especially important in teenagers, he adds. “With adolescents, I want them to take ownership of this. I don’t want their parents to push them through the motions.”

Since having as many as 36 20–30-minute TMS treatment sessions is inconvenient for many patients, researchers have been devising ways to shorten the time required for treatment.

One innovation shortened the length of each session to as little as 3 minutes. It’s called iTBS — intermittent theta burst stimulation –– which is another form of repeated magnetic pulses. Research has shown outcomes to be roughly similar to standard treatment.

In 2018, the FDA approved iTBS to treat depression in adults. Both NeuroStar and BrainsWay technologies are FDA approved for iTBS as well as standard TMS.

Another innovation has been to do multiple sessions in a single day to shorten the overall treatment length and see results sooner.

In 2020, researchers at Stanford University tested a new protocol called SAINT (Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression) on 22 patients. In SAINT, the researchers delivered an iTBS session of 10 minutes — each involving 1,800 pulses — 10 times per day, with 50 minutes between sessions, for 5 consecutive days.

SAINT is also unusual in that it uses fMRI brain scans — rather than less accurate MRI scans — to identify the exact target of the treatment in the DLPFC and another technology called neuronavigation to deliver the pulses more accurately to the target area.

The net result is a higher dose of magnetic stimulation delivered more accurately over a shorter period of time, and the results appear to be better than those of standard TMS treatments. In the original SAINT study, as well as a double-blind, randomized controlled follow-up, this protocol showed substantially better results than standard TMS for TRD — as high as 87 percent remission. Remission is said to have lasted about 12 months with no further treatment.

Dr. Manu sees a good deal of excitement in the clinical community for innovations to make TMS workable for more patients by modifying the SAINT protocol. “People are using it in all kinds of modified versions in different locations.”

TMS is generally well-tolerated and has no cognitive side effects.

The most common side effect is headaches, which are reported by about half of the patients receiving TMS. These usually fade throughout treatment, but over-the-counter pain relief can be taken if needed. “Out of many, many patients, I haven’t had anybody who stopped treatment because of headaches,” Dr. Manu reports.

Some patients also experience scalp pain or aching, which usually fades after the treatment. Other possible side effects include fatigue and nausea.  Temporary hearing loss can result if earplugs aren’t worn during the treatment.

Other rarer side effects of TMS include seizures, but there are no known lasting effects from a seizure related to TMS.

While Dr. Manu recommends that all his patients continue with psychotherapy while doing TMS, he also sometimes combines different TMS protocols to maximize patient response.

With a new patient, Dr. Manu begins with a standard 20-minute session with deep TMS once a day. “Everybody starts with standard because it’s the most non-controversial and has the most evidence behind it,” he notes. If by the mid-mark of treatment, the 15th to 18th session, he doesn’t see a sign of improvement in the patient’s symptoms, he may add 3–5 minutes of iTBS at the beginning of each session to prime or enhance treatment.

With patients who are not responding, or only partially responding, to TMS, Dr. Manu may also offer the option of switching to or adding ketamine — another promising new treatment for depression. “If I see that you’ve had a response, even a small response to TMS, then I would say, ‘Let’s continue,’” he says. “Maybe ramp it up a little bit, and add that 3-minute iTBS, and let’s start ketamine.’”

Dr. Manu sees combining treatments as becoming more common. “I think it’s the way of the future — instead of trying them sequentially, one after another, after another, you try to try them in synergy.”