Pilot Accelerated Theta Burst in Treatment-Resistant Bipolar Depression

February 2, 2026 updated by: Ian Kratter, Stanford University

Pilot Accelerated Theta Burst Stimulation in Treatment-Resistant Bipolar Depression

This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant bipolar depression. In this open-label study, all participants will receive accelerated theta-burst stimulation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 minutes over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been very successful in real-world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session over 4-6 weeks). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment times with some preliminary success. In a recent study, the investigators applied this accelerated paradigm in individuals with treatment-resistant depression (TRD), which showed a significant antidepressant effect (90% remission rate). Additionally, 3 participants from this study carried a bipolar TRD diagnosis and responded at minimum, equally as well, with no adverse events experienced or manic/hypomanic conversion observed during the treatment series. This study intends to further modify the parameters to create a more rapid form of this treatment for bipolar TRD, and look at the change in clinical measures and neuroimaging biomarkers.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94305
        • Stanford University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female, 18 to 80 years of age.
  • Able to provide informed consent.
  • Diagnosed with Bipolar Disorder and currently experiencing a Major Depressive Episode (MDE).
  • Meet the threshold on the total MADRS score of >/=20 at baseline.
  • In good general health, as ascertained by medical history.
  • If female, a status of non-childbearing potential or use of an acceptable form of birth control.
  • History of rTMS failure with FDA approved rTMS parameters is permitted.

Exclusion Criteria:

  • Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.
  • Female that is pregnant or breastfeeding.
  • Female with a positive pregnancy test at participation.
  • Total MADRS score of < 20 at study entry.
  • Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by DSM-IV-TR), with the exception of nicotine dependence.
  • Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific Phobia (unless one of these is comorbid and clinically unstable, and/or the focus of the participant's treatment for the past six months or more).
  • History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes.
  • Any Axis I or Axis II Disorder, which at screening is clinically predominant to their bipolar depression or has been predominant to their bipolar depression at any time within six months prior to screening.
  • Considered at significant risk for suicide during the course of the study.
  • Has a clinically significant abnormality on the screening examination that might affect safety, study participation, or confound interpretation of study results.
  • Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation.
  • Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.
  • History of positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates.
  • Current (or chronic) use of opiates.
  • History of epilepsy.
  • History of shrapnel or metal in the head or skull.
  • History of cardiovascular disease or cardiac event.
  • History of OCD.
  • History of autism spectrum disorder.
  • Current psychosis
  • Any change in medication of which the study PI is not aware of.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Accelerated intermittent theta burst treatment
All participants will receive accelerated intermittent theta-burst stimulation.
Device: Accelerated intermittent theta-burst treatment

All participants will receive accelerated intermittent theta-burst stimulation to the left DLPFC. Treatment will be targeted by utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold adjust to the skull to cortical surface distance.

Stimulation will be delivered to left DLPFC using the MagPRo stimulator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline Montgomery Asberg Depression Rating Scale (MADRS)
Time Frame: Baseline and immediately post-treatment (6 days post baseline)

A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.

The MADRS consists of ten questions. Each interview question is rated from 0 to 6 with an overall score of 60 or less. Higher scores indicate increasing depressive symptoms. A total score of 0 to 6 indicates the absents of depressive symptoms, 7 to 19 indicates mild depressive symptoms, 30 to 34 indicates moderate depressive symptoms, 35 to 60 indicates severe depressive symptoms.
Baseline and immediately post-treatment (6 days post baseline)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline Young Mania Rating Scale (YMRS)
Time Frame: Baseline and immediate post-treatment (6 days post baseline)

The Young Mania Rating Scale (YMRS) is one of the most frequently utilized rating scales to assess manic symptoms. The scale has 11 items and is based on the patient's subjective report of his or her clinical condition.

There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. These four items are given twice the weight of the others to compensate for poor cooperation from severely ill patients. The overall total score is a maximum of 60.

Typical YMRS baseline scores can vary a lot. They depend on the patients' clinical features such as mania (YMRS = 12), depression (YMRS = 3), or euthymia (YMRS = 2).
Baseline and immediate post-treatment (6 days post baseline)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Investigators

  • Principal Investigator: Ian Kratter, MD, PhD, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2019

Primary Completion (Actual)

December 30, 2023

Study Completion (Actual)

December 30, 2023

Study Registration Dates

First Submitted

April 18, 2019

First Submitted That Met QC Criteria

May 14, 2019

First Posted (Actual)

May 16, 2019

Study Record Updates

Last Update Posted (Actual)

February 4, 2026

Last Update Submitted That Met QC Criteria

February 2, 2026

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 49486

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

clintrials.gov

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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