Dorsomedial Prefrontal Cortex and the Antidepressant Efficacy of Theta Burst Stimulation in Depressed Patients

Dorsomedial Prefrontal Cortex and the Antidepressant Efficacy of Theta Burst Stimulation in Depressed Patients and Its Predictors

This study evaluates an association between different dosage and the antidepressant efficacy of theta burst stimulation in patients with treatment-resistant depression. In a double-blind design, All patients are randomized to three groups, i.e. standardized dosage intermittent theta-burst stimulation treatment, high dosage intermittent theta-burst stimulation treatment or sham treatment.

Study Overview

• Status: Completed
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Device: Active standardized iTBS-DMPFC; Device: Active high-dosage iTBS-DMPFC; Device: Sham standardized iTBS-DMPFC or high-dosage iTBS-DMPFC

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei City, Taiwan, 112
    • Department of Psychiatry, Taipei Veterans General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, 21 to 70 years of age.
• Diagnosed with the recurrent Major depressive disorder (MDD) and currently having a Major Depressive Episode (MDE)
• Participants failed to respond to at least one adequate antidepressant treatment in their current episode
• Participants have a Clinical Global Impression - Severity score of at least 4 and a total score of at least 18 on the Hamilton Depression Rating Scale (HDRS-17) at both screening and baseline visits ( Day -14 and Day 0)
• Participants must discontinue their antidepressant medications at least for one week ( at least two weeks if Fluoxetine) prior to the TMS intervention and keep antidepressant-free during the study duration.
• Participants also failed to respond to one complete left-sided DLPFC 10Hz rTMS/piTBS treatment course.

Exclusion Criteria:

• a lifetime psychiatric history of bipolar disorder, schizophrenia, psychotic disorders, or organic mental disorder including substance abuse and dependence (based on DSM-IV criteria)
• Participants with a lifetime medical history of major systemic illness and clinically significantly abnormal screening examination that might affect safety, study participation, or confound interpretation of study results.
• Participants with a lifetime medical history of neurological disorder records (e.g., stroke, seizure, traumatic brain injury, post brain surgery), brain implants (neurostimulators), cardiac pacemakers
• Women with breastfeeding or pregnancy
• Participants with a current strong suicidal risk (i.e., a score of 4 on item 3 of the HDRS-17)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active standardized iTBS-DMPFC; This active group will receive standardized dosage of intermittent theta-burst on dorsomedial prefrontal cortex(DMPFC)	Device: Active standardized iTBS-DMPFC; Participants in the standardized dosage(600 pulse) of intermittent TBS(iTBS) active stimulation group will receive 3-week three-pulse 50-Hz bursts administered every 200 milliseconds (at 5 Hz) at an intensity of 80% active motor threshold (MT) to bilateral DMPF, twice a day. Bilateral side DMPFC will be targeted by MRI-neuronavigation system. Stimulation will be delivered to the DMPFC using a Magstim stimulator.
Experimental: Active high-dosage iTBS-DMPFC; This active group will receive high dosage of intermittent theta-burst on dorsomedial prefrontal cortex(DMPFC)	Device: Active high-dosage iTBS-DMPFC; Participants in the standardized dosage(1800pulse) of intermittent TBS(iTBS) active stimulation group will receive 3-week three-pulse 50-Hz bursts administered every 200 milliseconds (at 5 Hz) at an intensity of 80% active motor threshold (MT) to bilateral DMPF, twice a day. Bilateral side DMPFC will be targeted by MRI-neuronavigation system. Stimulation will be delivered to the DMPFC using a Magstim stimulator.
Sham Comparator: Sham standardized iTBS-DMPFC or high-dosage iTBS-DMPFC; Patients in the sham group will receive the same standardized or high-dosage iTBS performing by a sham coil	Device: Sham standardized iTBS-DMPFC or high-dosage iTBS-DMPFC; Half of the patients in the sham group received 3-week the same standardized iTBS parameter stimulation (standardized sham-iTBS), and the other half received the same high dosage iTBS parameter stimulation using a sham coil (high dosage sham-rTMS), which also improved the blinding process

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in 17-item Hamilton Depression Rating Scale	the altered percentage of 17-item Hamilton Depression Rating Scale (range, 0 to 52, with higher scores indicating more depression)	Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate after 3-week treatment at the end of iTBS sessions and three and six month after.	improvement > 50 % of 17-item Hamilton Depression Rating Scale (range, 0 to 52, with higher scores indicating more depression)	Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation)
Remission rate after 3-week treatment	17-item Hamilton Depression Rating Scale ≤7 (range, 0 to 52, with higher scores indicating more depression)	Baseline, Week 1, Week 2, Week 3, Week 15(three-month after brain stimulation), Week 27(Six-month after brain stimulation)
Changes in Clinical Global Index	Clinical Global Index	Baseline, Week 1, Week 2, Week 3
Changes in depression severity, rated by self-reported	Depression and Somatic Symptoms Scale, range from 0 to 66 with higher scores indicating more depressive and somatic symptom.	Baseline, Week 1, Week 2, Week 3
Changes in Young Mania Rating Scale	Young Mania Rating Scale, range from 0 to 60 with higher scores indicating more severe manic symptoms.	Baseline, Week 1, Week 2, Week 3
Baseline treatment refractory level and the further antidepressant efficacy of brain stimulation	Maudsley staging method	Baseline, Week 3
Baseline brain connectivity and the further antidepressant efficacy of brain stimulation	baseline functional MRI	Baseline, Week 3
the change of brain connectivity after 3-week iTBS treatment	the change in brain connectivity	Baseline, Week 3
Baseline Life event stress scale and the further antidepressant efficacy of brain stimulation	Life event stress scale,range from 0 to 1467 with higher scores indicating more life event stress.	Baseline, Week 3
Changes in EEG band before and after brain stimulation	Perform rostral anterior cingulate cortex(rACC)-engaging cognitive task(RECT) before 1-st treatment	Day 1(pre-RECT, post RECT, post 1st treatment, pre-30th treatment)
Baseline single-pulse stimulation and the further antidepressant efficacy of brain stimulation	baseline single-pulse stimulation	Baseline, Week 3
Changes in single-pulse stimulation before and after brain stimulation	the change in single-pulse stimulation	Baseline, Week 3
Baseline paired-pulse stimulation and the further antidepressant efficacy of brain stimulation	baseline paired-pulse stimulation	Baseline, Week 3
Changes in paired-pulse stimulation before and after brain stimulation	the change in paired-pulse stimulation	Baseline, Week 3
Change in anxiosomatic cluster symptoms derived 17-item Hamilton Depression Rating Scale	the altered anxiosomatic cluster symptoms (range, 0 to 26, with higher scores indicating more severe anxiosomatic symptoms).The anxiosomatic cluster symptoms comprised nine items derived from HDRS-17: early insomnia, middle insomnia, slowness or retardation, psychic anxiety, autonomic anxiety, gastrointestinal symptoms, somatic symptoms, genital symptoms, and hypochondriasis.	Baseline, Week 1, Week 2, Week 3

Collaborators and Investigators

• Sponsor: Taipei Veterans General Hospital, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2019
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): January 31, 2021

Study Registration Dates

• First Submitted: July 26, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 30, 2019

Study Record Updates

• Last Update Posted (Actual): August 31, 2022
• Last Update Submitted That Met QC Criteria: August 28, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: 2018-07-011C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No