Dorsomedial Prefrontal Neuromodulation in Treatment-resistant Depression

Summary

Major depressive disorder (MDD) is a common and troublesome disorder, with high risk of physical and psychiatric comorbidity. At least one-third of patients could not achieve a response after several antidepressant trials, so-called treatment-refractory depression (TRD). The high-frequency repetitive transcranial magnetic stimulation (rTMS) or intermittent theta-burst stimulation (iTBS) at left-sided dorsolateral prefrontal cortex (DLPFC) have a response rate of 40-60%. Obviously, not all TRD patients achieve the remitted state after treatment with antidepressants or DLPFC-rTMS, which may result from the heterogeneity of MDD. More and more evidence, such as brain lesion studies, deep brain stimulation, open-labeled rTMS case series, and neuroimaging studies, suggests that dorsomedial prefrontal cortex (DMPFC) might play a more central role in the pathophysiology of major depression. The DMPFC demonstrated as a "dorsal nexus" phenomenon in depression, which means a unique brain region where cortical networks for affect regulation, default mode control and cognitive control coverage in depressed subjects but not in healthy persons. In addition, another meta-analysis of resting-state functional MRI (fMRI) demonstrated the abnormal functional connectivity from DMPFC. These abnormalities of networks were highly associated with several depressive symptoms such as anhedonia, emotional regulation, somatic markers, rumination, self-reflection, poor attention and poor decision-making. However, only a handful of studies investigated the brain stimulation targeting DMPFC and the further changes in brain functional connectivity. The clinical efficacy and the fMRI changes of prolonged intermittent theta-burst stimulation (piTBS) and 20Hz- rTMS targeting bilateral DMPFC were investigated, and the predictive value of baseline networks by fMRI for antidepressant responses was also assessed to find a reliable approach to gauge treatment response prospectively.

Conditions

• Treatment-resistant Depression
• Major Depressive Disorder

Interventions

DEVICE

Prolonged intermittent theta burst stimulation (piTBS)

Participants in the prolonged dosage (1800 pulse) of intermittent TBS (iTBS) active stimulation group will receive 2-week three-pulse 50-Hz bursts administered every 200 milliseconds (at 5 Hz) at an intensity of 80% active motor threshold (MT) to the bilateral DMPFC, twice a day. Stimulation will be delivered to the DMPFC using a stimulator.

DEVICE

20Hz rTMS

Participants in the 20 Hz rTMS (2000 pulse) active stimulation group will receive 2-week 2s- and-10s off, total 50 cycles at each hemisphere/session, at an intensity of 100% resting motor threshold (MT) to the bilateral DMPFC, twice a day. Stimulation will be delivered to the DMPFC using a stimulator.

DEVICE

sham control

Half of the patients in the sham group received 2-week the same prolonged iTBS parameter stimulation (sham- prolonged iTBS), and the other half received the same 20 Hz rTMS parameter stimulation using a sham coil (sham-20 Hz rTMS), which also improved the blinding process

Sponsors & Collaborators

• Taipei Veterans General Hospital, Taiwan

  lead OTHER_GOV

Principal Investigators

• Chih-Ming Cheng, M.D. · Taipei Veterans General Hospital, Taiwan

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-06-07

Primary Completion

2025-09-30

Completion

2025-12-31

Countries

• Taiwan

Study Locations