NCT07181226

High-Frequency vs. Theta-Burst TMS for Depression

High-Frequency vs. Theta-Burst TMS in Depression: Head-to-Head Double-Blind Randomized Trial With Six-week Follow-up

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 108 (actual)
• Sponsor: Krajská zdravotní, a.s. - Nemocnice Most, o.z. · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial was to learn if two different types of repetitive transcranial magnetic stimulation (rTMS) could help treat depression and anxiety in adults with major depressive disorder. The main questions it aimed to answer were: Did high-frequency rTMS and intermittent theta-burst stimulation (iTBS) both reduce depressive symptoms? Did one treatment lead to greater improvement in anxiety symptoms? Researchers compared people receiving high-frequency rTMS to those receiving iTBS to see if one worked better for mood and anxiety symptoms. Participants: Were randomly assigned to one of the two treatment groups. Received 10 stimulation sessions over two weeks (five sessions per week). Completed questionnaires and interviews on depression, anxiety, and stress before treatment, after two weeks, and again six weeks later.

Detailed description

This randomized, double-blind clinical trial evaluated two established repetitive transcranial magnetic stimulation (rTMS) protocols-high-frequency rTMS (HF-rTMS) and intermittent theta-burst stimulation (iTBS)-delivered in a shortened, two-week treatment schedule for adults with major depressive disorder (MDD). The purpose was to determine whether a condensed regimen could provide effective relief of depressive and anxiety symptoms while improving treatment feasibility. Design and Intervention A total of 108 participants with a primary diagnosis of MDD were randomized in a 1:1 ratio to receive either HF-rTMS (10 Hz stimulation) or iTBS, both targeting the left dorsolateral prefrontal cortex (DLPFC). Treatments were administered over 10 sessions in two consecutive weeks (five sessions per week). HF-rTMS protocol: 1500 pulses per session at 10 Hz, delivered in 10 trains of 15 seconds each with 50-second inter-train intervals. Total session time: approximately 12.5 minutes. iTBS protocol: 600 pulses per session, delivered as bursts of three 50 Hz pulses repeated at 200 ms intervals, with 2-second trains and 8-second inter-train intervals. Total session time: approximately 3 minutes and 20 seconds. Stimulation intensity for both protocols was set at 100% of the participant's individual resting motor threshold. Blinding and Assessments The trial employed a double-blind design: participants, clinical evaluators, and most research staff were unaware of treatment allocation. Independent clinicians performed structured interviews and validated rating scales before treatment (baseline), after two weeks of treatment, and at six-week follow-up. Outcomes and Rationale The primary outcomes were changes in depressive symptoms measured by the Hamilton Depression Rating Scale (HAMD) and the Zung Self-Rating Depression Scale (SDS), and changes in anxiety symptoms measured by the Hamilton Anxiety Rating Scale (HAMA) and the Beck Anxiety Inventory (BAI). Secondary outcomes included perceived stress and self-reported depressive symptomatology. This study was motivated by clinical and logistical considerations: standard rTMS protocols often require 4-6 weeks of treatment, which can be burdensome for patients and health systems. Evidence suggests that much of the therapeutic response occurs within the first 10-15 sessions, raising the possibility that shorter regimens may capture the critical therapeutic window. By directly comparing HF-rTMS and iTBS within a condensed protocol, this trial aimed to clarify their relative antidepressant and anxiolytic efficacy, evaluate the durability of short-course treatment, and inform optimized approaches to neuromodulation in depression.

Conditions

• Major Depression

Interventions

Type	Name	Description
DEVICE	High-frequency repetitive transcranial magnetic stimulation	High-frequency rTMS was delivered to the left dorsolateral prefrontal cortex using the 5 cm rule to localize the target site. Stimulation intensity was set at 100% of the resting motor threshold, determined by visible motor-evoked potentials in the right abductor pollicis brevis muscle. Each session consisted of 1500 pulses at 10 Hz, organized into 10 trains of 15 seconds (150 pulses per train) with 50-second inter-train intervals. Total stimulation time per session was approximately 12.5 minutes. A figure-of-eight coil (70BFX-LQC, Deymed Diagnostics) connected to a DuoMagXT-100 stimulator was used, with the coil positioned at \~45° from the midline, handle pointing posterolaterally.
DEVICE	Intermittent Theta Burst Stimulation	Intermittent theta-burst stimulation (iTBS) was delivered to the left dorsolateral prefrontal cortex using the 5 cm rule for target localization. Stimulation intensity was set at 100% of the resting motor threshold, determined by motor-evoked potentials in the right abductor pollicis brevis muscle. Each session consisted of 600 pulses delivered in bursts of three 50 Hz pulses repeated every 200 ms. Trains of 2 seconds were followed by 8-second inter-train intervals. Total stimulation time per session was approximately 3 minutes and 20 seconds. A figure-of-eight coil (70HF-LQC, Deymed Diagnostics) connected to a DuoMagXT-100 stimulator was used, with coil orientation \~45° from the midline, handle pointing posterolaterally.

Timeline

• Start date: 2022-05-01
• Primary completion: 2024-12-31
• Completion: 2025-04-30
• First posted: 2025-09-18
• Last updated: 2025-09-24

Locations

1 site across 1 country: Czechia