High-Frequency vs. Theta-Burst TMS for Depression

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.

Inclusion criteria

• Adults aged 18 to 90 years.
• Current major depressive disorder (MDD) as the primary diagnosis, confirmed according to the International Classification of Diseases, 10th Revision (ICD-10).
• All participants had to be evaluated by a board-certified psychiatrist trained in rTMS to confirm eligibility.
• Ability and willingness to provide written informed consent prior to study participation.

Exclusion criteria

• Presence of ferromagnetic or electronic implants in the head or neck (e.g., pacemakers, aneurysm clips, cochlear implants, deep brain stimulators).
• Known seizure disorders (such as epilepsy) or significantly increased risk of seizures.
• Other major neurological diseases or conditions that would interfere with safe rTMS administration.
• Active psychotic symptoms or a primary psychotic disorder.
• Acute manic episode or recent hospitalization for mania or other severe psychiatric instability.
• Ongoing electroconvulsive therapy (ECT) treatment.
• Medication changes made during the study.
• Inability to comply with the treatment schedule (e.g., attendance problems, logistical barriers).
• Any medical or psychiatric condition judged by the investigators to compromise safety or data integrity.