Rapid Acting TMS for Suicide Ideation in Depression

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Rapid Acting Transcranial Magnetic Stimulation for Suicide Ideation in Depression

Conditions
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Depressive Disorder, Major, Suicide

Intervention / Treatment
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* Device: Accelerated Theta Burst Stimulation
* Device: Sham Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 22-65 year old at the time of screening on voluntary or involuntary hold 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. 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). Meet the threshold on the MADRS and HAMD-17 with a total score of >/=20 at baseline. Not in a current state of mania (Young Mania Rating Scale) or psychosis (MINI) Have to be TMS naive In good general health, as ascertained by medical history. Scheduled with a psychiatrist Access to clinical rTMS after hospital discharge 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. No recent use (for the actual depressive episode) of rapid acting antidepressive agent (ketamine) Exclusion Criteria: 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. Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear History of epilepsy/ seizures (including history of withdrawal/ provoked seizures) Shrapnel or any ferromagnetic item in the head. 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. Autism Spectrum disorder A diagnosis of obsessive-compulsive disorder (OCD) The presence or diagnosis of prominent anxiety disorder, personality disorder, or dysthymia 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. Active substance use (<1 week) or intoxication verified by toxicology screen--of cocaine, amphetamines, benzodiazepines Cognitive impairment (including dementia) Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation) Current mania or psychosis Bipolar Affective Disorder I and primary psychotic disorders. Showing symptoms of withdrawal from alcohol or benzodiazepines IQ<70 Parkinsonism or other movement d/o determined by PI to interfere with treatment Desirous of getting ECT and previous intolerant exposure to ECT Any other indication the PI feels would comprise data No access to clinical rTMS after discharge. Previous TMS exposure. Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will receive either active or sham stimulation to the DLPFC. Patients will be randomized to either condition with a 50:50 chance.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Left Dorsolateral Prefrontal Cortex (L-DLPFC)<br>The accelerated theta burst stimulation protocol will be applied to the left dorsolateral prefrontal cortex (DLPFC) | Device: Accelerated Theta Burst Stimulation<br>* 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.<br>|
| Sham Comparator: Sham Stimulation<br>Sham (non-active) stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC) region | Device: Sham Stimulation<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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suicidality, neuromodulation, transcranial magnetic stimulation, depression