Coming Soon! Help for Treatment-Resistant Bipolar Depression

by Sonya Collins Health Writer

Bipolar disorder isn’t an easy condition to live with, even when its back-and-forth symptoms of energy-sapping depression and manic episodes are properly treated. But as many as 30% of people with this condition face an even greater struggle from treatment-resistant depression, with medication alone bringing little relief from symptoms. The good news: Help may be on the horizon. Increasing evidence suggests that transcranial magnetic stimulation (TMS), already FDA-approved for major depressive disorder, may help people with treatment-resistant bipolar depression, too.

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What Is TMS, Anyway?

In 2020, the FDA gave TMS—a noninvasive procedure using magnetic fields to stimulate nerve cells in the brain—“breakthrough” status for bipolar depression in a step toward wider approval. Currently, TMS is available off-label and in clinical trials—with documented success when used with anti-manic medication. “The closest thing we have to [it] is electric convulsive therapy and ketamine, but remission rates on those interventions are lower, and side effects higher,” says Nolan Williams, M.D., assistant professor of psychiatry and behavioral sciences at Stanford University.

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Can TMS Improve Other Therapy Outcomes?

Experts are hopeful this non-pharmaceutical treatment will soon become widely available. “With bipolar disorder, people often benefit from a combination of treatments,” says Alexandra Gold, a researcher in the department of psychological and brain sciences at Boston University. “One thing that’s really exciting about magnetic stimulation is that by relieving depression symptoms, it may make it easier for people to experience the maximum benefits of other treatments, such as psychotherapy.” More research needs to be done to learn if TMS ups efficacy of bipolar meds as well.

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What Happens During a TMS Treatment?

To undergo TMS, you sit beneath a machine with an electromagnetic coil on your scalp. Once activated with an electric current, the coil painlessly stimulates your prefrontal cortex, the region of your brain associated with depression. Experts don’t fully understand why it works—but they believe it may rouse areas of the brain that become inactive during depression. The procedure’s effects, researchers believe, depend on the brain region that’s being targeted, as well as the speed of the magnetic pulses and how often (and for how long) each treatment takes place.

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How Many Treatments Are Required?

A standard approach for TMS therapy treating stubborn clinical depression includes 30 treatments, administered five days per week for six consecutive weeks. Each treatment is 19 to 37 minutes. “Some people benefit from additional TMS treatment if, let’s say, they feel 50% better after 30 treatments, but not 100% better,” says Gustavo Kinrys, M.D., a psychiatrist in the bipolar clinic and research program at Massachusetts General Hospital in Boston. After additional treatments, he adds, some patients report experiencing full relief.

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Does Intensity Matter?

Higher doses of brain stimulation over shorter periods of time may be effective for people with severe depression. Researchers performed brain scans on 21 severely depressed people, some with bipolar depression, to pinpoint the area in each brain that showed signs of depression. Then, they directed the equivalent of six weeks of brain stimulation per day for five consecutive days to those regions. Nine out of 10 participants saw depressive symptoms abate. “TMS is able to push the system pretty significantly into mood improvement,” says study author Dr. Williams.

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How Effective Is TMS for Bipolar Disorder?

In a 2019 review in Brain and Behavior, researchers analyzed 23 clinical trials in which 559 people with bipolar disorder received either TMS or a placebo. Some participants were depressed when they received treatment, others were manic. A few participants had both mania and depression. “We found the treatment was especially helpful for reducing depressive symptoms, but results were mixed for mania,” says lead author Gold. About half of the people who received TMS for depression experienced some relief, with a third reporting full remission.

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Is TMS a Treatment—or a Cure?

TMS doesn’t cure bipolar depression, but it can have long-lasting effects. Eventually, symptoms return, and people need treatment again. People with severe bipolar depression who received intensive stimulation at Stanford saw their symptoms return about three to four months later. Still, other research shows that “many people stay well for years without requiring more treatments,” says Dr. Kinrys. Some individuals, he adds, may come in for maintenance treatment every few weeks to every few months, others for a booster treatment at random intervals, when they feel depression symptoms starting again.

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What Are the Pros and Cons of Doing TMS?

Because it requires a doctor’s visit, TMS may not be as convenient as, say, taking prescription medication every day at home. Transcranial magnetic stimulation can also be expensive, depending on whether or not your insurance covers it. But for nearly the one in three people with depression who don’t respond to medication, this treatment may be the one that finally brings relief. And compared to antidepressant medications—which can cause nausea, weight gain, fatigue, constipation, anxiety and loss of libido—the risks are minimal.

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Are There Negative Side Effects From TMS?

The good news is that TMS doesn’t require surgery or sedation with anesthesia. In rare cases—less than 1%—it can cause a seizure, or even trigger a manic episode for about 3% of people with bipolar disorder, says Dr. Kinrys. But TMS-induced mania, he adds, is less serious and easier to treat than antidepressant-induced mania. Other possible side effects: Discomfort on the scalp in the spot beneath the magnetic coil and headaches (up to 5% of people report them). But both headaches and scalp discomfort tend to go away after a few treatments.

Sonya Collins
Meet Our Writer
Sonya Collins

Sonya Collins is an Atlanta-based independent journalist and editor. She covers health, medicine and scientific research, with a special emphasis on genetics and personalized medicine. Sonya is a regular contributor to WebMD Magazine, WebMD.com, CURE, and Staying Sharp. She is a contributing editor at The Conversation and WebMD.com.