From Scientific American
Transcranial magnetic stimulation(TMS) isn’t a new therapy, but it can be an effective last line of defense against this frequently disabling disorder.
Depression and antidepressant use are at all-time highs in the year 2017, but for about a third of those affected, depression still doesn’t get better with medication—and for these patients, transcranial magnetic stimulation (TMS), which uses powerful magnets to stimulate brain cells noninvasively, can be a viable option.
To be clear, TMS isn’t new; it was first approved by the FDA in 2008. What’s new is that the evidence for its safety and effectiveness has only gotten stronger. TMS is now generally covered by insurance companies for treatment-resistant depression, and new studies have shown that combining it with traditional treatments like psychotherapy can lead to significantly higher response rates. Some scientists also now believe TMS can be a dominant therapy compared to antidepressants, based on its lower cost, higher net monetary benefit and better quality of life outcomes produced. Although there are still many questions about TMS left unanswered, it is a treatment with a strong presence in fighting depression and much promise as personalized TMS grows closer to becoming a reality.
WHEN MEDICATION FAILS: TREATMENT-RESISTANT DEPRESSION
According to the World Health Organization, an estimated 350 million people worldwide suffer from depression, making it the leading cause of disability worldwide. As many as 30 percent of people with depression are resistant to medication, and show suicide thoughts and attempts, and an overall poor quality of life. With traditional treatment options ineffective, these patients need a solution.
One such person is 63-year-old Brenda Griffith, a retired nurse, mother and grandmother.
“My depression started prior to my late 30s when my life wasn’t great. I couldn’t think clearly a lot of the time and it was difficult working as a nurse. I couldn’t enjoy life at all,” Griffith says.
Griffith was diagnosed with depression in the early 1990s by her psychiatrist, James Beeghly, and was subsequently prescribed nearly every antidepressant medication.
Antidepressants are the most commonly used treatment for depression. New data from the CDC reports that an estimated one in eight Americans over the age of 12 have taken antidepressants. Most patients with depression report some improvement in response to medication, but for Griffith, the antidepressants just made things worse.
“My depression progressively got worse as I took the medications. I took over 12 medications over years, and nothing seemed to work,” Griffith said. “What’s worse is I also experienced terrible side effects like nausea all the time.”
It turns out, Griffith had treatment-resistant depression, a term used to refer to cases of depression where the patient still exhibits symptoms of depression following two or more antidepressant treatments.
As another treatment option, Griffith started electroconvulsive therapy (ECT), an invasive therapy used for more severe cases of depression that passes electric currents through the brain. ECT is used to treat severe cases of treatment-resistant depression but carries risks and side effects including memory loss, confusion, and physical effects—all of which were experienced by Griffith.
“ECT saved my life, but it wasn’t enough for me to function normally. I had to give up nursing,” Griffith said. “I was on ECT for 15 years but because of my long-term ECT, learning new things was difficult. I was so afraid of the memory loss getting worse, I didn’t want to do it anymore.”
With both antidepressants and ECT unable to improve Griffith’s life, she began her last option: TMS, which had been approved by the FDA for treatment-resistant depression.
THE TMS EXPERIENCE FOR DEPRESSION
With transcranial magnetic stimulation, a small electromagnetic coil is placed against a patient’s head at a precise location. For patients with depression, this location is the left frontal cortex of the brain that has historically been shown to be less active in people with depression.
TMS attempts to fix the lack of activity in the left frontal cortex through providing daily stimulations that rewire and cause the cortex to become more excitable and produce a long-lasting antidepressant effect.
The noninvasive nature of TMS is what makes it appealing compared to ECT. When TMS was first clinically used, there was some hesitation in its widespread adoption due to concerns about its safety, mainly whether it would accidentally cause seizures. However, recent studies show that there are no major safety concerns with TMS.
“The term noninvasive refers to the fact that no surgery is required,” said Aaron Boes, a TMS expert at the University of Iowa. “In fact, the safety data for TMS is very strong—there are no major cognitive side-effects in patients and the risk of seizures is less than 0.1 percent.”
The standard TMS treatment happens in 40-minute sessions each day of the week for 4–6 weeks. Each individual treatment session can cost $300–$500 and there are typically 30 to 40 sessions in a course of TMS therapy. Insurance coverage for TMS used to be spotty, but now, the majority of insurance companies and federal programs cover TMS therapy for treatment-resistant depression.
During a standard TMS session, a patient can read or talk with other people. Furthermore, the patient can drive to and from the TMS sessions, so they don’t need someone to constantly supervise them.
“The whole treatment setup was fantastic—the coil that provides the stimulation feels like a gentle woodpecker on your head. I wasn’t nervous about it at all, I was comfortable,” Griffith says. “It’s a mild discomfort when you first start but you get used to it and the side effects are so limited. It can be noisy, but you wear earplugs.”
Three weeks into her TMS treatment, Griffith’s condition started improving. People around Griffith, including her psychiatrist, noticed the differences in her since the treatment.
“TMS made Brenda better and more like her natural self,” Beeghly says. “When I first started seeing her as my patient many years ago, I saw a picture of her smiling. I didn’t see that kind of smile from her for decades. I saw it with TMS. It’s been liberating for her. She has more control over her life in many ways. Instead of sleeping, she now spends time with her family.”
On average, patients tend to respond to TMS after two to four weeks, and the response rates are encouraging.
“For patients who have tried and failed at least two antidepressants in the current episode, the data is the rule of thirds,” says Mark George, a pioneer in using TMS for depression who leads the Brain Stimulation Laboratory at the Medical University of South Carolina. “About one third will get remission with no symptoms left, another one third will get response with their symptoms cut in half, and unfortunately one third will get no response.”
About 58 percent of TMS-treated patients will have a positive response, defined as a reduction in their depression by 50 percent of more, and 37 percent of all patients will have complete remission of depression.
A recent cost-effectiveness analysis study conducted by scientists identified TMS as the dominant therapy compared to antidepressant medication given the current costs of both. In the study, scientists used simulation modeling to determine that TMS can be provided at a lower cost, and a higher net monetary benefit with better quality of life outcomes compared to antidepressant medication. Despite these statistics, there is a lot of treatment variability with TMS.
“TMS can produce a durable treatment response, but it is not a cure. It tends to last around nine months, with variability, with continued treatment often needed,” Boes says.
WHAT WE STILL DON’T KNOW
Maintaining and extending the TMS treatment response is an active area of research. TMS experts believe this can be accomplished with individualized treatment protocols.
“Like many areas of medicine, TMS is a treatment that might someday be customized so it is delivered in a way that is personalized to match the individual patient’s brain abnormality,” says Linda Carpenter, a TMS expert and professor of psychiatry at Brown University.
Carpenter also adds that before personalized TMS services become a reality, scientists still need to discover how to make the clinical improvement from TMS last longer before a depressive relapse occurs. Most scientists studying TMS believe that greater consistency in treatment responses and longer-lasting effects could be achieved if they were able to identify more precise and personalized stimulation targets in patients’ brains.
“Many people think that better science behind the targeting, precisely where the TMS ‘coil’ is placed on the scalp, could bring about better antidepressant results,” Carpenter says. “There is also interest in learning about other activities such as psychotherapy, brain training, or exercise that might be synergistically paired with TMS therapy to get the maximal therapeutic effect.”
In fact, scientists just recently published a study that combined TMS and psychotherapy to treat patients with depression. What is exciting is that they observed response and remission rates significantly higher than those predicted by the “rule of thirds.”
There are even more questions about TMS that, if answered, could improve treatment. For instance, scientists still do not exactly know what frequency and intensity is needed for the stimulation, how many sessions should be administered and how the treatment works to bring about the resolution of depression symptoms?
“We still do not fully understand the exact translational cascade that TMS starts that ends up fixing depression,” George says.
Despite these unanswered questions, the evidence supporting the clinical use of TMS for treatment-resistant depression is still strong. A recent study of treatment in 42 U.S.-based clinical TMS sites that treated 307 patients with major depressive disorder confirmed that TMS is an effective treatment for people unable to benefit from antidepressants. TMS is increasingly viable and, according to Carpenter, some scientists believe there could potentially be a future generation of similar brain stimulation devices that are safe for administration at home.
Although TMS is not a miracle cure and other treatments should be tried first, it is more viable and validated today than ever before, and provides an option for people like Griffith with treatment-resistant depression. Griffith hopes her experience can be educational for other individuals and their families in similar situations.
“Depression affects your life, and it affects your family,” Griffith says. “But you have to be open to changes. You have to fight depression and know that there are options.”