Adjuvant Accelerated piTBS for Reducing Suicidal Ideation in TRD Patients

NCT ID: NCT06372834

Last Updated: 2025-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-29
• Study Completion Date: 2024-12-20

Brief Summary

In this double-blind, randomized, sham-controlled trial, the investigators aimed to examine the effect of accelerated piTBS on suicide risk in a group of treatment-resistant patients with MDD (i.e., TRD), using an extensive suicide assessment scale the primary outcome. The investigators hypothesized that this intensified treatment protocol would be safe in TRD patients with suicide ideations and would result in significant decreases in suicide risk in the active treatment condition as compared to the sham condition.

Detailed Description

Less than half of patients with major depressive disorder (MDD) remit after first-line therapy (i.e., pharmacotherapy and/or psychotherapy). A progressively smaller proportion of patients remit with each subsequent medication trial, and a remission rate of only 10-15% after a fourth antidepressant trial. Patients with MDD are considered to have a treatment-resistant depression (TRD) whey they do not achieve response to first-line antidepressants. Repetitive Transcranial Magnetic Stimulation (rTMS) applied over the DLPFC for modulating brain activity and network connectivity has well-documented positive effects on major depressive disorder (MDD), especially TRD. rTMS research in treating MDD has shown a dose-response relationship and more recently, studies have shown a trend towards administering more stimuli over a shorter period of time and at higher frequencies leading to accelerated protocols. An optimized rTMS parameter called intermittent theta burst stimulation (iTBS) is a novel protocol that consists of intermittently delivering bursts of 3 TMS pulses at high frequency (50 Hz) every 200 ms for 2 s (5Hz) every 10 s (total 600 pulses), allowing for greater long-lasting effects on cortical excitability and a more important number of rTMS pulses to be delivered in a shorter duration than standardized high frequency (HF) rTMS protocols. iTBS induces a long-term potentiation (LTP)-like effect by increasing the postsynaptic concentration of calcium ions and has been applied to treat MDD. iTBS has been proved to be safe and well tolerated and to have antidepressant properties. Prolonged iTBS (piTBS, total 1800 pulses) has been recently applied to treat MDD with favorable antidepressant properties. An accelerated protocol of piTBS has been recently approved to treat medication-refractory MDD by FDA.

MDD is associated with a 2.3 fold increase in prevalence of suicidal ideation as compared to the general population. The lifetime rate of death due to suicide among MDD patients is 15-20%. Research indicates that 30% of TRD patients will attempt suicide during their lifetime, which is a two-to-four times greater proportion than MDD patients who respond to treatment. Research indicates that rTMS improves several preconditions for suicide, including mood, memory, attention, executive functioning. rTMS is thought to have molecular effects similar to those seen with electroconvulsive therapy (ECT), which is effective in treating suicidal patients, such as increased BDNF, increased monoamine turnover and normalization of the hypothalamic-pituitary-adrenal axis. Some research indicates that rTMS may reduce suicidal ideations of patients with MDD. However, powered sham-controlled rTMS clinical trials focusing on the efficacy to improve suicide risks are limited.

The study aims to investigate the efficacy of accelerated piTBS over the left DLPFC as an add-on therapy to improve suicide ideations in TRD patients. Moreover, it provides data on other secondary outcomes and neurophysiological data for this intervention condition.

Conditions

Major Depressive Disorder; Treatment-Resistant Depression; Suicide Ideations

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

piTBS (active, N=50)

The piTBS sessions will be delivered using the Magstim Rapid2 stimulator (Magstim Company, Ltd, Whitland, Wales, UK, SA340HR) with a 70-mm air-cooled figure-eight coil (Magstim D70 Air film coil). The piTBS protocol consists of 3-pulse 50-Hz bursts given every 200 ms (at 5 Hz) for 2 s at 8-s intervals for 60 cycles. A 2-s train of piTBS will be repeated every 10 s for a total of 1800 pulses per session. The intensity of stimulation will be set at 90% resting motor threshold (RMT), as measured from the right first dorsal interosseous muscle by a handheld 700-mm figure-of-eight coil (Magstim D70 alpha coil). The Beam F3 method will be used for coil positioning to target the left dorsolateral prefrontal cortex. The piTBS protocol will be scheduled for 3 sessions per working day for 2 weeks (i.e., a total of 30 sessions over 2 weeks). Three sessions of the piTBS per day will be separated by at least 60 mins.

Group Type: EXPERIMENTAL

piTBS being delivered using the Magstim Rapid2 stimulator

Intervention Type: DEVICE

Magstim Rapid2 stimulator (Magstim Company, Ltd, Whitland, Wales, UK, SA340HR). See detail in arm/group descriptions regarding the intervention.

piTBS (sham, N=50)

The patients in the sham piTBS condition will receive the same piTBS regimen and exact positioning of the coil, but stimulations will be delivered using a commercial identical-looking figure-8 sham coil (Magstim D70 Air film sham coil) that can produce a similar sound and sensations but induce neither magnetic pulses nor current in the cortex.

Group Type: SHAM_COMPARATOR

piTBS being delivered using the Magstim Rapid2 stimulator

Intervention Type: DEVICE

Magstim Rapid2 stimulator (Magstim Company, Ltd, Whitland, Wales, UK, SA340HR). See detail in arm/group descriptions regarding the intervention.

Interventions

piTBS being delivered using the Magstim Rapid2 stimulator

Magstim Rapid2 stimulator (Magstim Company, Ltd, Whitland, Wales, UK, SA340HR). See detail in arm/group descriptions regarding the intervention.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Subjects aged 20-65 years, met criteria for DSM-V major depressive disorder.
• A depression severity score of 18 or more on the 17-item Hamilton Rating Scale for Depression (HRSD-17) as well as a score of 1 or more on the item of the HDRS-17 (item 3).
• Meeting criteria for TRD defined as no clinical response to at least one adequate trial of one major class of antidepressants.
• Having been receiving stable antidepressant medications regimen for more than 4 weeks before enrollment and having their original medication regimen unchanged throughout the trial.

Exclusion Criteria

• Having MDD with psychotic features, bipolar disorder, schizophrenia, organic brain syndrome or active substance (except for tobacco and coffeine) use disorder.
• Having previous intracranial surgery and ferromagnetic metallic implants in the head.
• History of brain abnormalities (e.g., brain neoplasms, arteriovenous malformations, meningitis, encephalitis, epilepsy, neurodegenerative disorders).
• Pregnancy at enrollment.
• History of treatment with electroconvulsive therapy (ECT) or no response to rTMS over the left DLPFC.
• Those who had attempted a suicide within six months from the screening date.
• Skin lesions on scalp at the area of coil application.
• In addition to those listed above, those who were deemed unsuitable for participating in this clinical trial by the medical judgment of the investigator due to other reasons (e.g., lack of competence to consent to research or any other contraindications to receiving rTMS).

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tri-Service General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hsin-An Chang, MD

Attending Psychiatrist, Department of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hsin-An Chang, MD

Role: PRINCIPAL_INVESTIGATOR

Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Locations

Tri-service general hospital

Taipei, , Taiwan

Countries

Taiwan

Other Identifiers

B202205178

Identifier Type: -

Identifier Source: org_study_id