Transcranial magnetic stimulation (gently!) jump-starts a depressed brain

Transcranial magnetic stimulation (TMS) sounds like something from a horror film or a cousin of electroshock therapy. Fortunately, it’s not like that at all. TMS is an emerging, non-invasive therapy that responds to the biology of depression by stimulating underactive neurons in the brain. 

TMS is not a treatment of first resort. It is used to treat people who have severe or protracted depression. It offers a non-pharmaceutical alternative for people who may have tried medication and therapy, but still don’t feel like themselves. For that group of people, depression can be a discouraging and open-ended condition.

Depression is the result of shrinkage in two areas of the brain, the hippocampus (the centre of memory) and the cerebral cortex (the base of thought). This shrinkage reduces the size of nerve cells in the affected parts of the brain, and constricts their connections to other areas of the brain—ultimately affecting the brain’s ability to relay messages or instructions effectively throughout the body. The communications delay produces some of the common effects of depression: brain fog, fluctuating mood, insomnia and that characteristic heaviness that just doesn’t seem to lift. It’s helpful to imagine these nerves as an electrical circuit, wired throughout the brain and body. Depression slows the circuitry’s functioning. TMS sends a mild, stimulating current to fire up activity in the slow parts of the circuit. Much like using jump starters on a car battery (but more gently!), TMS tries to jump-start brains.

Paul Fitzgerald is a research professor of psychiatry at Monash University in Australia. He completed a fellowship at the University of Toronto, where he initially used TMS as a tool for “investigating aspects of brain function and dysfunction in people with schizophrenia.” Gradually, his studies regarding schizophrenia expanded into the possibility of using TMS as a broader therapeutic tool for treating a range of mental illnesses.

Fitzgerald has fulfilled his ambition by establishing a broader TMS research program at home in Australia. He explains that TMS revives neurons which have become underactive as a result of mental illness. The therapy can be a non-invasive alternative or a complement to medicine or other treatments. The quick pulses of TMS produce magnetic fields that induct electrical currents into the brain. When one site of the brain’s neural circuit is stimulated, it sets off a chain reaction: each neuron responds to the renewed activity of the neuron before it. This enables messages to be delivered more effectively from one side of the brain to the other, overcoming the depressive lag in response caused by previously incapacitated neurons.

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Paul Fitzgerald is a research professor of psychiatry at Monash University in Australia. 

How does TMS treatment feel?

“Screening for eligibility is relatively straightforward," Fitzgerald says. "There [are] very few people who can’t have a course of TMS." Because TMS is regulated nationally, specific eligibility criteria vary from country to country.

Patients who have decided to undertake a course of TMS can expect odd sensations and possibly slight discomfort during their sessions. Each treatment begins with testing to calculate the optimum settings. “It’s a bit of an odd procedure," Fitzgerald says. "Essentially, we put the coil not at the front of the brain where we [will] do treatment. We put it further back, over the area of the brain that controls the muscles in the hand on the opposite side of the body.” Diagonals like this frequently arise in the discussion of TMS treatment.

The electrical pulses are then gradually turned up depending on the patient's response—an adjustment which also conveniently helps the body to get used to the sensation. “We keep doing that until it gets to the point where it starts to make the nerve cells in that motor area of the brain fire," Fitzgerald explains. "And when they fire, what happens is that it sends signals to cause the muscle [to] twitch in [the patient’s] hand. You feel this sort of tapping sensation in your head and your hand starts [making] single twitches which you can’t control.” The twitching is completely normal and signifies the extent of the electrical pulse that the body can tolerate. Treatment can then begin.

TMS treatment requires the coils to be placed most commonly on the front left-hand side of the brain. Depending on the protocols of the clinic, each treatment can vary between five and 30 minutes, with the patient feeling sensations which Fitzgerald describes as “benign”. He goes on to say that a lot of “people with longer protocols fall asleep during treatments . . . they’re bored of sitting in the chair every day. Occasionally there will be some patients who find it uncomfortable, if not painful, if the coil or the magnetic field just happens to be going right where there happens to be a nerve.”

As with most measures of sensitivity, some people are more susceptible to pain than others. However, if a patient is struggling or experiencing twitching in the temple or eyelid, the TMS coils may be repositioned to minimise discomfort. Other patients take a Panadol in anticipation of a tension headache afterward.

Aside from the headaches, side effects are minimal, and patients are permitted to drive home after their treatment. However, prospective TMS patients are informed of a very rare side effect: a seizure similar to epileptic seizures. Fitzgerald explains: “We’re targeting an area of the brain in people with depression that’s underactive. We’re trying to reactivate that area of the brain. If we provide the pulses too long or too high in intensity we just occasionally, randomly, under normal parameters, overstimulate the neurons. They could then discharge spontaneously and trigger a seizure.” This effect is  so rare that Fitzgerald has not witnessed it during his 20-year practice.

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Scans of the brain when it is depressed and after it undergoes TMS therapy.

TMS treatments are repeated on a daily basis for between 20 and 35 sessions. It takes a minimum of 20 treatments to determine whether TMS is effective for any individual, and 35 is the absolute maximum length of one course.

How is the effectiveness of TMS assessed? While technicians will give patients questionnaires to gauge how they feel from a scientific standpoint, Fitzgerald says that they place most emphasis on patient testimonies: “Occasionally [we] see someone who had been unwell for 15 years . . . turn around and say, ‘I’m better, this is what I used to be like.’”

Fitzgerald also looks for the changes that treatment makes in individual lives. “You also want to see that it works, that those changes are relevant [to] people’s lives in the real world," he says. "[You want to know that] they’re going back to work, reconnecting with family and friends, [that] they’re able to get out of bed and do things.”

Depression is classed as a recurrent condition, which means it can return at any time. That heightens the importance of broadening the therapeutic toolkit. TMS can be part of that toolkit, an alternative or complement to conventional medicine with significant potential rewards.

TMS statistics are promising. The Harvard Medical School health blog by Dr Adam P. Stern summarises the results of TMS:

Approximately 50% to 60% of people with depression who have tried and failed to receive benefit from medications experience a clinically meaningful response with TMS. About one-third of these individuals experience a full remission, meaning that their symptoms go away completely. It is important to acknowledge that these results, while encouraging, are not permanent. Like most other treatments for mood disorders, there is a high recurrence rate. However, most TMS patients feel better for many months after treatment stops, with the average length of response being a little more than a year.

If the treatment has worked once, it will often work again, and patients who have experienced temporary benefits can opt for maintenance courses of TMS. 

The present and the future of TMS 

Statistics New Zealand reports that national mental health “data showed a significant increase in the proportion of people with poor mental wellbeing, up from 22 percent in 2018 to 28 percent in 2021.” Every effective treatment is good news and TMS looks like a promising option.

However, TMS is a resource-intensive treatment, not yet widely available. While there are many clinics dotted around Australia, New Zealand has only five TMS machines available in private clinics. TMS treatment is also expensive, with each individual session now costing between 200 and 300 NZD.

Accounting for one component of its cost, each TMS treatment session must be individually controlled by TMS technicians trained in the technology and its application to mental health. Because TMS does not require an anaesthetic, the prerequisites for technician training include a non-specialist background in healthcare and an appropriate degree.

These practical challenges will need to be overcome if TMS is to become generally accessible. Current results and future, potential applications for TMS suggest that there will be wider demand very soon.

Fitzgerald is optimistic about the future of TMS. The American Food and Drug Administration (FDA) has now approved TMS treatments for smoking cessation and for people with obsessive-compulsive disorder (OCD). Additional research is ongoing, with clinical trials applying TMS to Alzheimer's disease, schizophrenia, attention deficit hyperactivity disorder (ADHD), and other conditions affecting brain function. The FDA is monitoring TMS trials.

The FDA has approved the use of TMS for Americans aged 18 years and older. Research is also underway to assess whether TMS is appropriate for children and adolescents, with initial results suggesting that children have similar success rates to their older counterparts. The research is not yet sufficient for FDA approval, but the extension of TMS treatments to different demographics and conditions is rapidly evolving.

There is no guarantee that TMS will be right for any individual. However, for those who have lived with the weight of depression for years, TMS might offer one more path back to feeling like themselves.