Bilateral Accelerated Theta Burst in Treatment-Resistant Bipolar Depression

• ClinicalTrials.gov Identifier: NCT03953417
• Recruitment Status: Recruiting
• First Posted: May 16, 2019
• Last Update Posted: August 19, 2019
• Sponsor: Stanford University
• Information provided by (Responsible Party): Nolan R, Stanford University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Treatment Resistant Depression	Device: Bilateral accelerated intermittent theta-burst treatment	Not Applicable

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, 5 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Bilateral Accelerated Theta Burst Stimulation in Treatment-Resistant Bipolar Depression
• Actual Study Start Date: July 1, 2019
• Estimated Primary Completion Date: July 1, 2021
• Estimated Study Completion Date: July 30, 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: Bilateral accelerated intermittent theta burst treatment; All participants will receive accelerated intermittent theta-burst stimulation.

Device: Bilateral accelerated intermittent theta-burst treatment; All participants will receive bilateral accelerated intermittent theta-burst stimulation to the left and right 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 and right-DLPFC using the MagPRo stimulator.

Outcome Measures

Primary Outcome Measures :

1. Change from baseline Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline and immediately post-treatment ]

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

   The MADRS uses a 0 to 6 severity scale, scored following the interview. Scoring/Interpretation: Higher scores indicate increasing depressive symptoms. ... Cut-off points include: 0 to 6 - symptom absent, 7 to 19 - mild depression, 30 to 34 - moderate, 35 to 60 - severe depression.

2. Change from baseline Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline and 1-month post-treatment ]

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

   The MADRS uses a 0 to 6 severity scale, scored following the interview. Scoring/Interpretation: Higher scores indicate increasing depressive symptoms. ... Cut-off points include: 0 to 6 - symptom absent, 7 to 19 - mild depression, 30 to 34 - moderate, 35 to 60 - severe depression.

3. Change from baseline functional connectivity as measured by MR imaging [ Time Frame: Baseline and immediate post-treatment ]
   Pre- and post resting state functional connectivity and structural T1-weighted MRI scans to determine the anti-correlated LDLPFC and SCC treatment location. The identified cluster with the greatest anti-correlation between the LDLPFC and SCC will have been utilized for the targeted aiTBS treatment. This algorithm will have also been applied to the post-imaging sessions to give measurements of voxel-wise blood flow in this anti-correlation targeted brain ROI.
4. Change from baseline functional connectivity as measured by MR imaging [ Time Frame: Baseline and 1-month post-treatment ]
   Pre- and 1 month post resting state functional connectivity and structural T1-weighted MRI scans to determine the anti-correlated LDLPFC and SCC treatment location will be administered. The identified cluster with the greatest anti-correlation between the LDLPFC and SCC will have been utilized for the targeted aiTBS treatment. This algorithm will have also been applied to the one month post treatment sessions to give measurements of voxel-wise blood flow in this anti-correlation targeted brain ROI.
5. Change from baseline Young Mania Rating Scale (YMRS) [ Time Frame: Baseline and immediate post-treatment ]

   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.

   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).

Secondary Outcome Measures :

1. Change from baseline Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline and immediate post-treatment ]

   A suicidal ideation rating scale created by researchers at Columbia University.

   A trained rater will administer the Columbia Suicide Severity Rating Scale (C-SSRS). This questionnaire was developed to rate suicidal ideation and behavior.

   It rates a person's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent and behaviors.

   The scale identifies specific behaviors which may be indicative of a person's intent to complete suicide. An person exhibiting even a single behavior identified by the scale was 8 to 10 times more likely to complete suicide.

2. Change from baseline Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline and 1-month post-treatment ]

   A suicidal ideation rating scale created by researchers at Columbia University.

   A trained rater will administer the Columbia Suicide Severity Rating Scale (C-SSRS). This questionnaire was developed to rate suicidal ideation and behavior.

   It rates a person's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent and behaviors.

   The scale identifies specific behaviors which may be indicative of a person's intent to complete suicide. An person exhibiting even a single behavior identified by the scale was 8 to 10 times more likely to complete suicide.

3. Change from baseline Hamilton Rating Scale for Depression (HAM-6) [ Time Frame: Baseline and immediate post-treatment ]
   A 6-item clinical assessment measuring depressive symptoms. Scores range from 0-24 with scores >5 indicating clinical levels of depressive symptoms.
4. Change from baseline Hamilton Rating Scale for Depression (HAM-6) [ Time Frame: Baseline and follow-up every 2 weeks for 6 months by telephone ]
   A 6-item clinical assessment measuring depressive symptoms. Scores range from 0-24 with scores >5 indicating clinical levels of depressive symptoms.
5. Change from baseline Hamilton Rating Scale for Depression (HAM-21) [ Time Frame: Baseline and immediate post-treatment ]

   A 21-item clinical assessment measuring depressive symptoms. Although the HAM-D form lists 21 items, the scoring is based on the first 17. It generally takes 15-20 minutes to complete the interview and score the results. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2.

   Sum the scores from the first 17 items. 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression

   ≥ 23 = Very Severe Depression

6. Change from baseline Hamilton Rating Scale for Depression (HAM-21) [ Time Frame: Baseline and 1-month post-treatment ]

   A 21-item clinical assessment measuring depressive symptoms. Although the HAM-D form lists 21 items, the scoring is based on the first 17. It generally takes 15-20 minutes to complete the interview and score the results. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2.

   Sum the scores from the first 17 items. 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression

   ≥ 23 = Very Severe Depression

7. Change from baseline Beck Depression Inventory (BDI-II) [ Time Frame: Baseline and immediate post-treatment (up to 10 minutes to complete the questionnaire) ]

   The Beck Depression Inventory (BDI-II) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression. BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.

   Scores: 0-13= minimal depression, 14-19=mild depression, 20-28=moderate depression, 29-63=severe depression

8. Change from baseline Beck Depression Inventory (BDI-II) [ Time Frame: Baseline and 1-month post-treatment (up to 10 minutes to complete the questionnaire) ]

   The Beck Depression Inventory (BDI-II) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression. BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.

   Scores: 0-13= minimal depression, 14-19=mild depression, 20-28=moderate depression, 29-63=severe depression

9. Change from baseline Young Mania Rating Scale (YMRS) [ Time Frame: Baseline and weekly for 8 weeks and every two weeks (up to 6 months) ]

   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.

   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).

10. Change in Scale of Suicidal Ideation (SSI) score [ Time Frame: Baseline and immediate post-treatment ]

    19-item clinician administered assessment to measure the intensity, pervasiveness, and characteristics of suicidal ideation in adults.

    Scores range from 0-38, with a score higher than 6, indicating active suicidal ideation.

Other Outcome Measures:

1. Change from baseline in the Hopkins Verbal Learning Test- Revised (HVLT-R) [ Time Frame: Baseline and immediate post-treatment ]
   The Hopkins Verbal Learning Test - Revised (HVLT-R) is given to assess learning and recall of verbal information. The HVLT-R is a list-learning task with three learning trials, a 20-minute delayed recall, and a recognition paradigm following the delayed recall. There are six alternate forms that allow for serial evaluation.
2. Change from baseline in the Hopkins Verbal Learning Test- Revised (HVLT-R) [ Time Frame: Baseline and 1-month post-treatment ]
   The Hopkins Verbal Learning Test - Revised (HVLT-R) was given to assess learning and recall of verbal information. The HVLT-R is a list-learning task with three learning trials, a 20-minute delayed recall, and a recognition paradigm following the delayed recall. There are six alternate forms that allow for serial evaluation.
3. Change from baseline in the Brief Visuospatial Memory Test - Revised (BVMT-R) [ Time Frame: Baseline and immediate post-treatment ]
   The Brief Visuospatial Memory Test - Revised (BVMT-R) was given to measure learning and memory of visuospatial stimuli. The BVMT-R is a task that requires the participant to learn an array of simple geometric figures over three learning trials. There is a delayed recall after 25 minutes and a recognition task following the delay. There is also a copy task following the memory recall and recognition portions of the test. There are six alternate forms that allow for serial evaluation.
4. Change from baseline in the Brief Visuospatial Memory Test - Revised (BVMT-R) [ Time Frame: Baseline and 1-month post-treatment ]
   The Brief Visuospatial Memory Test - Revised (BVMT-R) was given to measure learning and memory of visuospatial stimuli. The BVMT-R is a task that requires the participant to learn an array of simple geometric figures over three learning trials. There is a delayed recall after 25 minutes and a recognition task following the delay. There is also a copy task following the memory recall and recognition portions of the test. There are six alternate forms that allow for serial evaluation.
5. Change from baseline in the Delis Kaplan Executive Function System (D-KEFS): Trail Making Test [ Time Frame: Baseline and immediate post-treatment ]

   Delis Kaplan Executive Function System (D-KEFS): Trail Making Test Description: The Trail Making Test was used to measure combined visuomotor and executive functioning including sequencing and cognitive switching. The test also provides measures of visual scanning and motor speed.

   Reference: DELIS DC, KRAMER JH, KAPLAN E, HOLDNACK J. Reliability and validity of the Delis-Kaplan Executive Function System: An update. J Int Neuropsychol Soc. 2004;10(02)

6. Change from baseline in the Delis Kaplan Executive Function System (D-KEFS): Trail Making Test [ Time Frame: Baseline and 1-month post-treatment ]

   Delis Kaplan Executive Function System (D-KEFS): Trail Making Test Description: The Trail Making Test was used to measure combined visuomotor and executive functioning including sequencing and cognitive switching. The test also provides measures of visual scanning and motor speed.

   Reference: DELIS DC, KRAMER JH, KAPLAN E, HOLDNACK J. Reliability and validity of the Delis-Kaplan Executive Function System: An update. J Int Neuropsychol Soc. 2004;10(02)

7. Change from baseline in the Delis Kaplan Executive Function System (D-KEFS): Color-Word Interference [ Time Frame: Baseline and immediate post-treatment ]

   Delis Kaplan Executive Function System (D-KEFS): Color-Word Interference Description: The Color-Word Interference test provides a measure of cognitive inhibition and cognitive switching. There are also word reading and color naming trials that provide a measure of reading and color naming speed.

   Reference: DELIS DC, KRAMER JH, KAPLAN E, HOLDNACK J. Reliability and validity of the Delis-Kaplan Executive Function System: An update. J Int Neuropsychol Soc. 2004;10(02)

8. Change from baseline in the Delis Kaplan Executive Function System (D-KEFS): Color-Word Interference [ Time Frame: Baseline and 1-month post-treatment ]

   Delis Kaplan Executive Function System (D-KEFS): Color-Word Interference Description: The Color-Word Interference test provides a measure of cognitive inhibition and cognitive switching. There are also word reading and color naming trials that provide a measure of reading and color naming speed.

   Reference: DELIS DC, KRAMER JH, KAPLAN E, HOLDNACK J. Reliability and validity of the Delis-Kaplan Executive Function System: An update. J Int Neuropsychol Soc. 2004;10(02)

9. Change from baseline in the Delis Kaplan Executive Function System (D-KEFS): Verbal Fluency [ Time Frame: Baseline and immediate post-treatment ]

   Delis Kaplan Executive Function System (D-KEFS): Verbal Fluency Description: The Verbal Fluency test provides measures of phonemic and semantic fluency, as well as a trial that involves cognitive switching combined with semantic fluency.

   Reference: DELIS DC, KRAMER JH, KAPLAN E, HOLDNACK J. Reliability and validity of the Delis-Kaplan Executive Function System: An update. J Int Neuropsychol Soc. 2004;10(02)

10. Change from baseline in the Delis Kaplan Executive Function System (D-KEFS): Verbal Fluency [ Time Frame: Baseline and 1-month post-treatment ]

    Delis Kaplan Executive Function System (D-KEFS): Verbal Fluency Description: The Verbal Fluency test provides measures of phonemic and semantic fluency, as well as a trial that involves cognitive switching combined with semantic fluency.

    Reference: DELIS DC, KRAMER JH, KAPLAN E, HOLDNACK J. Reliability and validity of the Delis-Kaplan Executive Function System: An update. J Int Neuropsychol Soc. 2004;10(02)

11. Change in baseline Altman Self-Rating Mania Scale (ASRM) [ Time Frame: Baseline and immediate post-treatment ]

    The ASRM is a 5-item self rating mania scale, designed to assess the presence and/or severity of manic symptoms.

    Interpretation:

    • A score of 6 or higher indicates a high probability of a manic or hypomanic condition
    • A score of 6 or higher may indicate a need for treatment and/or further diagnostic workup
    • A score of 5 or lower is less likely to be associated with significant symptoms of mania
12. Change in baseline Altman Self-Rating Mania Scale (ASRM) [ Time Frame: Baseline and daily time-points (for 5 days) ]

    The ASRM is a 5-item self rating mania scale, designed to assess the presence and/or severity of manic symptoms.

    Interpretation:

    • A score of 6 or higher indicates a high probability of a manic or hypomanic condition
    • A score of 6 or higher may indicate a need for treatment and/or further diagnostic workup
    • A score of 5 or lower is less likely to be associated with significant symptoms of mania
13. Change in baseline Altman Self-Rating Mania Scale (ASRM) [ Time Frame: Baseline and all post-treatment time-points (weekly for 8 weeks and every two weeks up to 6 months) ]

    The ASRM is a 5-item self rating mania scale, designed to assess the presence and/or severity of manic symptoms.

    Interpretation:

    • A score of 6 or higher indicates a high probability of a manic or hypomanic condition
    • A score of 6 or higher may indicate a need for treatment and/or further diagnostic workup
    • A score of 5 or lower is less likely to be associated with significant symptoms of mania
14. Change from baseline Internal State Scale (ISS) [ Time Frame: Baseline and daily time points (for 5 days) ]

    Independent assessment of manic and depressive symptoms by self- rating scale characteristics and implications for the study of mania.

    The ISS contains a series of visual analogue scale (VAS) items consisting of statement followed by a by eleven "bins" (equivalent to 0-10, 11-20, …91-100). In Likert-based scoring, the first bin is scored as zero, the second as 10, and so on to theeleventh bin which is scored as 100.

    Scoring:

    >155: (Hypo)Mania >155: Mixed State <155: Euthymia <155: Depression

15. Change from baseline Internal State Scale (ISS) [ Time Frame: Baseline and immediate post-treatment ]

    Independent assessment of manic and depressive symptoms by self- rating scale characteristics and implications for the study of mania.

    The ISS contains a series of visual analogue scale (VAS) items consisting of statement followed by a by eleven "bins" (equivalent to 0-10, 11-20, …91-100). In Likert-based scoring, the first bin is scored as zero, the second as 10, and so on to the eleventh bin which is scored as 100.

    Scoring:

    >155: (Hypo)Mania >155: Mixed State <155: Euthymia <155: Depression

16. Change from baseline Internal State Scale (ISS) [ Time Frame: Baseline and recurrent post-treatment time-points (weekly for 8 weeks and every two weeks up to 6 months) ]

    Independent assessment of manic and depressive symptoms by self- rating scale characteristics and implications for the study of mania.

    The ISS contains a series of visual analogue scale (VAS) items consisting of statement followed by a by eleven "bins" (equivalent to 0-10, 11-20, …91-100). In Likert-based scoring, the first bin is scored as zero, the second as 10, and so on to the eleventh bin which is scored as 100.

    Scoring:

    >155: (Hypo)Mania >155: Mixed State <155: Euthymia <155: Depression

17. Change from baseline Inventory of Depressive Symptoms (IDS-SR) [ Time Frame: Baseline and daily time points (for 5 days) ]

    30-item self-report questionnaire used to assess depressive symptoms and severity of depression. Responses are scored by summing responses of the 30 items to obtain a total score ranging from 0 to 84.

    Scoring:

    0-13= no depression 14-25= mild depression 26-38= moderate depression 39-48= severe depression 49-84= very severe depression

18. Change from baseline Inventory of Depressive Symptoms (IDS-SR) [ Time Frame: Baseline and immediate post-treatment ]

    30-item self-report questionnaire used to assess depressive symptoms and severity of depression. Responses are scored by summing responses of the 30 items to obtain a total score ranging from 0 to 84.

    Scoring:

    0-13= no depression 14-25= mild depression 26-38= moderate depression 39-48= severe depression 49-84= very severe depression

19. Change from baseline Inventory of Depressive Symptoms (IDS-SR) [ Time Frame: Baseline and recurrent post-treatment time-points (weekly for 8 weeks and every two weeks up to 6 months) ]

    30-item self-report questionnaire used to assess depressive symptoms and severity of depression. Responses are scored by summing responses of the 30 items to obtain a total score ranging from 0 to 84.

    Scoring:

    0-13= no depression 14-25= mild depression 26-38= moderate depression 39-48= severe depression 49-84= very severe depression

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).
• Participants must currently be on a stable and adequate dose of a mood stabilizer and medication intake must remain stable throughout study enrollment.
• Participants may also have a history of intolerance to antidepressant medications. These patients with the intolerance history will not be required to be currently taking an antidepressant medication.
• Meet the threshold on the total HAMD17 score of >/=20 at both screening and baseline visits (Day -5/-14 and Day 0).
• Meet the threshold on the BDI-II, with a score of >/=17 at both screening and baseline visits (Day -5/-14 and Day 0).
• Meet the threshold on the total MADRS score of >/=20 at both screening and baseline visits (Day -5/-14 and Day 0).
• 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.
• History of ECT failure or intolerance 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 HAMD-17 score of < 20 at the screen or baseline visits.
• Total MADRS score of < 20 at the screen or baseline visits.
• Total BDI-II score of < 17 at the screen or baseline visits.
• 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.

Contacts and Locations

Contacts

Contact: Romina Nejad, MSc; 650-497-3933; rnejad@stanford.edu

Locations

United States, California

Stanford University; Recruiting

Palo Alto, California, United States, 94305

Contact: Nolan Williams, MD nolanw@stanford.edu

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Nolan Williams, MD; Stanford University

More Information

Publications:

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.

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.

Pascual-Leone A, Rubio B, Pallardó F, Catalá MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7.

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. Review.

Jelić MB, Milanović SD, Filipović 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.

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. Review.

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.

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.

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.

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. Review.

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.

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.

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.

Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):253-8. Epub 2002 Dec 27.

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. Epub 2005 Jun 23.

Greicius MD, Supekar K, Menon V, Dougherty RF. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex. 2009 Jan;19(1):72-8. doi: 10.1093/cercor/bhn059. Epub 2008 Apr 9.

• Responsible Party: Nolan R, Assistant Professor, Director of Interventional Psychiatry Clinical Research, Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford University
• ClinicalTrials.gov Identifier: NCT03953417
• Other Study ID Numbers: 49486
• First Posted: May 16, 2019
• Last Update Posted: August 19, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: clintrials.gov

• 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

Keywords provided by Nolan R, Stanford University:

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

Additional relevant MeSH terms:

Depression; Depressive Disorder; Bipolar Disorder; Depressive Disorder, Treatment-Resistant; Behavioral Symptoms; Mood Disorders; Mental Disorders; Bipolar and Related Disorders