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This study evaluates the antidepressant effects of an accelerated schedule of theta-burst stimulation, termed accelerated intermittent theta-burst stimulation (aiTBS), in individuals with borderline personality disorder (BPD) or trait and comorbid mood depressive disorder (MDD) or bipolar II disorder in a current mood depressive episode (MDE).
This project aims to measure and modulate a mood depressive episode (MDE) in individuals with borderline personality disorder (BPD) trait and comorbid mood depressive disorder (MDD) or bipolar II disorder in a current mood depressive episode (MDE). This study will test the antidepressant effect of aiTBS stimulation over the left dorsolateral prefrontal cortex (L-DLPFC), and aiTBS stimulation over the dorsomedial prefrontal cortex (DMPFC) compared with sham.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Left Dorsolateral Prefrontal Cortex (L-DLPFC) | Active Comparator | The accelerated theta burst stimulation protocol will be applied to the left dorsolateral prefrontal cortex (L-DLPFC) |
|
| Dorsomedial Prefrontal Cortex (DMPFC) | Active Comparator | The accelerated theta burst stimulation protocol will be applied to the dorsomedial prefrontal cortex (DMPFC) |
|
| Sham stimulation | Sham Comparator | Sham (non-active) stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC) region |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Left Dorsolateral Prefrontal Cortex (L-DLPFC) | Device | Participants who are randomly assigned to this group will receive active iTBS (intermittent theta burst stimulation) to the left DLPFC. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth). Stimulation will be delivered using the Magventure Magpro X100 TMS system. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the clinician rated Montgomery-Asberg Depression Rating Scale (MADRS-C) in active L-DLPFC vs. sham aiTBS. | A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.The MADRS-C has an overall score range from 0-60, with higher scores corresponding to higher levels of depression. | At baseline (pre-intervention), during the intervention and immediately after the intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the clinician rated Montgomery-Asberg Depression Rating Scale (MADRS-C) in active DMPFC vs. sham aiTBS. | A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders.The MADRS-C has an overall score range from 0-60, with higher scores corresponding to higher levels of depression. | At baseline (pre-intervention), during the intervention and immediately after the intervention. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nolan Williams, MD | Stanford University | Study Director |
| David Spiegel, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford Hospital | Stanford | California | 94305 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20439832 | Background | 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. | |
| 8547583 |
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Patients will be randomized to receive: active L-DLPFC stimulation, active DMPFC stimulation, or sham stimulation. Group size ratio will be 1:1:1.
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|
| Dorsomedial Prefrontal Cortex (DMPFC) | Device | Participants who are randomly assigned to this group will receive active iTBS (intermittent theta burst stimulation) to the DMPFC. Stimulation intensity will be standardized at 100% of resting motor threshold (adjusted for cortical depth). Stimulation will be delivered using the Magventure Magpro X100 TMS system. |
|
| Sham Stimulation | Device | Participants who are randomly assigned to this group will receive sham stimulation to the left DLPFC. Sham stimulation will be delivered using the Magventure Magpro X100 TMS system. |
|
| Feasibility of aiTBS in individuals with BPD and comorbid MDD or BAD II in a current MDE as defined by retention rates | Retention rates will be determined as research follow-up rate ≥80% | At baseline (pre-intervention), during the intervention and immediately after the intervention. |
| Feasibility of aiTBS in individuals with BPD and comorbid MDD or BAD II in a current MDE as defined by recruitment rate | Recruitment rate will be determined by actual recruitment/recruitment milestones | At baseline (pre-intervention), during the intervention and immediately after the intervention. |
| Safety of aiTBS in individuals with BPD and comorbid MDD or BAD II in a current MDE as defined by rate of suicidal behaviors | Rate of suicidal behaviors will be determined by number of participants that committed a SB/total number of participants | At baseline (pre-intervention), during the intervention and immediately after the intervention. |
| Background |
| 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. |
| 8684201 | Background | Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6. |
| 27604566 | Background | Abdallah CG, Averill LA, Collins KA, Geha P, Schwartz J, Averill C, DeWilde KE, Wong E, Anticevic A, Tang CY, Iosifescu DV, Charney DS, Murrough JW. Ketamine Treatment and Global Brain Connectivity in Major Depression. Neuropsychopharmacology. 2017 May;42(6):1210-1219. doi: 10.1038/npp.2016.186. Epub 2016 Sep 8. |
| 24629537 | Background | Liston C, Chen AC, Zebley BD, Drysdale AT, Gordon R, Leuchter B, Voss HU, Casey BJ, Etkin A, Dubin MJ. Default mode network mechanisms of transcranial magnetic stimulation in depression. Biol Psychiatry. 2014 Oct 1;76(7):517-26. doi: 10.1016/j.biopsych.2014.01.023. Epub 2014 Feb 5. |
| 26717528 | Background | Green KL, Brown GK, Jager-Hyman S, Cha J, Steer RA, Beck AT. The Predictive Validity of the Beck Depression Inventory Suicide Item. J Clin Psychiatry. 2015 Dec;76(12):1683-6. doi: 10.4088/JCP.14m09391. |
| 30761601 | Background | Ballard ED, Reed JL, Szczepanik J, Evans JW, Yarrington JS, Dickstein DP, Nock MK, Nugent AC, Zarate CA Jr. Functional Imaging of the Implicit Association of the Self With Life and Death. Suicide Life Threat Behav. 2019 Dec;49(6):1600-1608. doi: 10.1111/sltb.12543. Epub 2019 Feb 13. |
| 31825760 | Background | Tello N, Harika-Germaneau G, Serra W, Jaafari N, Chatard A. Forecasting a Fatal Decision: Direct Replication of the Predictive Validity of the Suicide-Implicit Association Test. Psychol Sci. 2020 Jan;31(1):65-74. doi: 10.1177/0956797619893062. Epub 2019 Dec 11. |
| 31481688 | Background | Light SN, Bieliauskas LA, Taylor SF. Measuring change in anhedonia using the "Happy Faces" task pre- to post-repetitive transcranial magnetic stimulation (rTMS) treatment to left dorsolateral prefrontal cortex in Major Depressive Disorder (MDD): relation to empathic happiness. Transl Psychiatry. 2019 Sep 3;9(1):217. doi: 10.1038/s41398-019-0549-8. |
| 29560909 | Background | Baeken C, Duprat R, Wu GR, De Raedt R, van Heeringen K. Subgenual Anterior Cingulate-Medial Orbitofrontal Functional Connectivity in Medication-Resistant Major Depression: A Neurobiological Marker for Accelerated Intermittent Theta Burst Stimulation Treatment? Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Oct;2(7):556-565. doi: 10.1016/j.bpsc.2017.01.001. Epub 2017 Jan 20. |
| 24388670 | Background | Downar J, Geraci J, Salomons TV, Dunlop K, Wheeler S, McAndrews MP, Bakker N, Blumberger DM, Daskalakis ZJ, Kennedy SH, Flint AJ, Giacobbe P. Anhedonia and reward-circuit connectivity distinguish nonresponders from responders to dorsomedial prefrontal repetitive transcranial magnetic stimulation in major depression. Biol Psychiatry. 2014 Aug 1;76(3):176-85. doi: 10.1016/j.biopsych.2013.10.026. Epub 2013 Nov 28. |
| 27378888 | Background | Duprat R, De Raedt R, Wu GR, Baeken C. Intermittent Theta Burst Stimulation Increases Reward Responsiveness in Individuals with Higher Hedonic Capacity. Front Hum Neurosci. 2016 Jun 16;10:294. doi: 10.3389/fnhum.2016.00294. eCollection 2016. |
| 31787757 | Background | Schmaal L, van Harmelen AL, Chatzi V, Lippard ETC, Toenders YJ, Averill LA, Mazure CM, Blumberg HP. Imaging suicidal thoughts and behaviors: a comprehensive review of 2 decades of neuroimaging studies. Mol Psychiatry. 2020 Feb;25(2):408-427. doi: 10.1038/s41380-019-0587-x. Epub 2019 Dec 2. |
| 30819549 | Background | Gartner M, Aust S, Bajbouj M, Fan Y, Wingenfeld K, Otte C, Heuser-Collier I, Boker H, Hattenschwiler J, Seifritz E, Grimm S, Scheidegger M. Functional connectivity between prefrontal cortex and subgenual cingulate predicts antidepressant effects of ketamine. Eur Neuropsychopharmacol. 2019 Apr;29(4):501-508. doi: 10.1016/j.euroneuro.2019.02.008. Epub 2019 Feb 26. |
| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| D001883 | Borderline Personality Disorder |
| D003863 | Depression |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D010554 | Personality Disorders |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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