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New Research into Treatment for Bipolar Depression

Bipolar Depression

Johns Hopkins psychiatrists study whether an unconventional transcranial magnetic stimulation (TMS) yields more rapid improvements in patients.

Psychiatry researchers are embarking on a pilot study to see if a novel form of transcranial magnetic stimulation (TMS) can yield more rapid improvements for patients with treatment-resistant depression in the setting of a bipolar 1 disorder diagnosis.

TMS is a noninvasive method of brain stimulation that uses an insulated coil placed over the scalp to send brief magnetic pulses into the brain. It has been used for years in patients with major depression, but the process is relatively slow, with sessions lasting an hour a day for up to six weeks.

Kevin Li

“What we’re hoping to achieve is that these patients will have a good, robust but also pretty rapid improvement of their depression.” — Kevin Li

The new trial will evaluate intermittent theta-burst stimulation, which the Food and Drug Administration has approved for treatment-resistant major depression, for patients with bipolar 1 disorder who have depressive episodes. The theta-burst pattern of stimulation better mimics naturally occurring activity in the brain that is responsible for learning and memory, explains research psychiatrist and study co-investigator Irving Reti, and it seems to be more efficient at treating depression then what has been used conventionally for TMS. In the trial, patients will receive multiple short sessions of TMS per day, totaling 18,000 pulses, compared to a typical TMS session of one dose of 3,000 pulses.

Participants will first come for a baseline visit to gather information about medical history, diagnoses, medication use and symptoms, says psychiatry postdoctoral fellow Kevin Li, who will be working on the study. Next, they will receive a functional MRI scan to map brain activity, specifically in the left dorsolateral prefrontal cortex. That information will be fed into an algorithm developed to guide researchers to the precise area of the brain to target with TMS.

Then, the patient will go to the hospital for five days of outpatient TMS treatments, receiving 10 sessions per day. Each block of treatment will last 10 minutes, and each will be followed by a 50-minute break, during which researchers will assess any improvements or adverse effects. They also will measure progress using the Montgomery-Åsberg Depression Rating Scale (MADRS), a diagnostic questionnaire.

“What we’re hoping to achieve is that these patients will have a good, robust but also pretty rapid improvement of their depression,” Li says. Patients likely will need to remain on maintenance medications.

The pilot will recruit five patients each at Johns Hopkins and the University of Texas at Austin. “The hope is that if this pilot is successful, it will provide preliminary evidence and data to support a larger trial to formally test the approach, leveraging the National Network of Depression Centers,” says principal investigator Peter Zandi, the Arlene and Robert Kogod Professor of Mood Disorders in the Department of Psychiatry and Behavioral Sciences and a professor of mental health at the Johns Hopkins Bloomberg School of Public Health.

The target population is adults over the age of 22 with bipolar 1 disorder who are currently experiencing a major depressive episode. To be included, they need to have failed at least one adequately dosed bipolar depression treatment of first-line medication, and they must be on a stable anti-manic regimen.


For more information or to refer a patient, email


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