Rapid Acting TMS for Suicide Ideation in Depression

Depressive Disorder, Major Clinical Trial

Official title:

Rapid Acting Transcranial Magnetic Stimulation for Suicide Ideation in Depression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05100004
• Other study ID #: 58808
• Status: Recruiting
• Phase: N/A
• Start date: November 7, 2021
• Est. completion date: September 2025

Study information

• Verified date: November 2023
• Source: Stanford University
• Contact: Jean-Marie Batail, MD, PhD
• Phone: 650-497-3933
• Email: jmbatail[@]stanford.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the effects of an accelerated schedule of theta-burst stimulation, termed accelerated intermittent theta-burst stimulation (aiTBS), on the neural networks underlying explicit and implicit suicidal cognition in inpatients with major depressive disorder.

Description:

Investigators recently developed a form of neuromodulation termed Stanford Neuromodulation Therapy (SNT). SNT-induced remission is associated with significant reductions in the functional connectivity of the neural network underlying explicit suicidal cognition (between sgACC-DMN). This project aims to further elucidate the SNT induced neural network changes underlying explicit suicidal cognition.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age 22-65 year old at the time of screening on voluntary or involuntary hold

2. Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information.

3. Diagnosed with Major Depressive Disorder (MDD) or Bipolar Affective Disorder II (BAPD II), according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).

Endorse suicidal ideation (score =9 on the SSI-M).

4. Meet the threshold on the MADRS and HAMD-17 with a total score of >/=20 at baseline.

5. Not in a current state of mania (Young Mania Rating Scale) or psychosis (MINI)

6. Have to be TMS naive

7. In good general health, as ascertained by medical history.

8. Scheduled with a psychiatrist

9. Access to clinical rTMS after hospital discharge

10. If participant is of childbearing potential and not already pregnant, must agree to use adequate contraception prior to study and for the duration of study participation.

11. No recent use (for the actual depressive episode) of rapid acting antidepressive agent (ketamine)

Exclusion Criteria:

1. Any abnormalities indicated on previous MRI scans e.g. structural neurological condition, more subcortical lesions than would be expected for age, stroke affecting stimulated area or connected areas or any other clinically significant abnormality that might affect safety, study participation, or confound interpretation of study results.

2. Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear

3. History of epilepsy/ seizures (including history of withdrawal/ provoked seizures)

4. Shrapnel or any ferromagnetic item in the head.

5. Pregnancy: The effects of rTMS on the developing human fetus are incipient and still uncertain (25). Pregnant women will not be enrolled into this study. Women of childbearing potential must agree to use adequate contraception (hormonal / barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Females of childbearing-age, will have a pregnancy test prior to receiving each rTMS stimulation session. Should a woman become pregnant or suspects she is pregnant while participating in this study, she should inform study staff.

6. Autism Spectrum disorder

7. A diagnosis of obsessive-compulsive disorder (OCD)

8. The presence or diagnosis of prominent anxiety disorder, personality disorder, or dysthymia

9. 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.

10. Active substance use (<1 week) or intoxication verified by toxicology screen--of cocaine, amphetamines, benzodiazepines

11. Cognitive impairment (including dementia)

12. Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation)

13. Current mania or psychosis

14. Bipolar Affective Disorder I and primary psychotic disorders.

15. Showing symptoms of withdrawal from alcohol or benzodiazepines

16. IQ<70

17. Parkinsonism or other movement d/o determined by PI to interfere with treatment

18. Desirous of getting ECT and previous intolerant exposure to ECT

19. Any other indication the PI feels would comprise data

20. No access to clinical rTMS after discharge.

21. Previous TMS exposure.

22. Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO).

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Suicide

Intervention

Device:
• Accelerated Theta Burst Stimulation
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.
• Sham Stimulation
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.

Locations

Country	Name	City	State
United States	Stanford Hospital	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (14)

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Biol Psychiatry. 2014 Sep 1;76(5):430. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in suicidal ideation as measured by the modified Scale for Suicide Ideation (m-SSI).	The modified Scale for Suicide (m-SSI) is an 18-item clinician rated scale that measures suicidal ideation. Each item is scored from 0-3. Scores are summed for 1 total score. Higher scores indicate more severe suicidal ideation. Investigators will assess change in m-SSI scores at the post-inpatient treatment completion (day 2-7).	At baseline (day 0) and at post-inpatient treatment completion (day 2-7)
Secondary	Rates of remission immediately after treatment in the Montgomery-Åsberg Depression Rating Scale (MADRS) score.	The Montgomery-Åsberg Depression Rating Scale (MADRS), is a ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.; Remission is defined as MADRS =10.	At baseline (day 0) and at post-inpatient treatment completion (day 2-7)
Secondary	Rates of response immediately after treatment in the Montgomery-Åsberg Depression Rating Scale (MADRS) score.	The Montgomery-Åsberg Depression Rating Scale (MADRS), is a ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.; Response is defined as a reduction of >/=50% of MADRS baseline score.	At baseline (day 0) and at post-inpatient treatment completion (day 2-7)