Pilot Accelerated Theta Burst in Treatment-Resistant Bipolar Depression

NCT03953417 | Completed Results FDA Device

• 1 other identifier: 49486
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Treatment Resistant Depression

Keywords

Bipolar Disorder; Treatment Resistant Depression; Transcranial Magnetic Stimulation (TMS); Theta Burst

Outcome Measures

Primary Outcomes (1)

• Change From Baseline Montgomery Asberg Depression Rating Scale (MADRS)

  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 Outcomes (1)

• Change From Baseline Young Mania Rating Scale (YMRS)

  Baseline and immediate post-treatment (6 days post baseline)

Study Arms (1)

Accelerated intermittent theta burst treatment

EXPERIMENTAL

All participants will receive accelerated intermittent theta-burst stimulation.

Device: Accelerated intermittent theta-burst treatment

Interventions

Accelerated intermittent theta-burst treatment DEVICE

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.

Accelerated intermittent theta burst treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Palo Alto, California, 94305, United States

Location

Related Publications (16)

• George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.

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• George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.

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• Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3.

  PMID: 26850210 BACKGROUND

• Jelic MB, Milanovic SD, Filipovic SR. Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. Clin Neurophysiol. 2015 May;126(5):1016-23. doi: 10.1016/j.clinph.2014.09.003. Epub 2014 Sep 16.

  PMID: 25281475 BACKGROUND

• Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28.

  PMID: 25450537 BACKGROUND

• Plewnia C, Pasqualetti P, Grosse S, Schlipf S, Wasserka B, Zwissler B, Fallgatter A. Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. J Affect Disord. 2014 Mar;156:219-23. doi: 10.1016/j.jad.2013.12.025. Epub 2013 Dec 28.

  PMID: 24411682 BACKGROUND

• Prasser J, Schecklmann M, Poeppl TB, Frank E, Kreuzer PM, Hajak G, Rupprecht R, Landgrebe M, Langguth B. Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. World J Biol Psychiatry. 2015 Jan;16(1):57-65. doi: 10.3109/15622975.2014.964768. Epub 2014 Nov 28.

  PMID: 25430687 BACKGROUND

• Daskalakis ZJ. Theta-burst transcranial magnetic stimulation in depression: when less may be more. Brain. 2014 Jul;137(Pt 7):1860-2. doi: 10.1093/brain/awu123. Epub 2014 May 15. No abstract available.

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• Thut G, Pascual-Leone A. A review of combined TMS-EEG studies to characterize lasting effects of repetitive TMS and assess their usefulness in cognitive and clinical neuroscience. Brain Topogr. 2010 Jan;22(4):219-32. doi: 10.1007/s10548-009-0115-4. Epub 2009 Oct 28.

  PMID: 19862614 BACKGROUND

• Holtzheimer PE 3rd, McDonald WM, Mufti M, Kelley ME, Quinn S, Corso G, Epstein CM. Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. Depress Anxiety. 2010 Oct;27(10):960-3. doi: 10.1002/da.20731.

  PMID: 20734360 BACKGROUND

• Fung PK, Robinson PA. Neural field theory of synaptic metaplasticity with applications to theta burst stimulation. J Theor Biol. 2014 Jan 7;340:164-76. doi: 10.1016/j.jtbi.2013.09.021. Epub 2013 Sep 21.

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• Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995 Oct;34(4):537-41. doi: 10.1002/mrm.1910340409.

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• Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9673-8. doi: 10.1073/pnas.0504136102. Epub 2005 Jun 23.

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  PMID: 18403396 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Bipolar Disorder

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Bipolar and Related Disorders

Limitations and Caveats

There are no limitations and caveats

Results Point of Contact

• Title: Principal Investigator
• Organization: Stanford University

nbassano@stanford.edu

650-736-2233

Study Officials

• Ian Kratter, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor, Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center

Study Record Dates

• First Submitted: April 18, 2019
• First Posted: May 16, 2019
• Study Start: July 1, 2019
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2023
• Last Updated: February 4, 2026
• Results First Posted: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)