About this trial

This randomized, rater-blinded clinical trial evaluates the effectiveness, safety, and tolerability of continuous theta burst stimulation (cTBS) in adults with generalized anxiety disorder (GAD). Participants will be randomly assigned in a 1:1 ratio to receive cTBS targeting either the right posterior parietal cortex (R-PPC) or the right dorsolateral prefrontal cortex (R-DLPFC). Participants may be psychotropic-medication naïve or may continue stable psychotropic medication according to the protocol-defined medication stability criteria.

The primary objective is to compare changes in anxiety symptom severity, measured using the Hamilton Anxiety Rating Scale (HAM-A), from baseline to the end-of-treatment assessment. Secondary and exploratory assessments include treatment response and remission, quality of life, sleep quality, cognitive function, safety and tolerability, resting electroencephalography (EEG), and transcranial magnetic stimulation combined with EEG (TMS-EEG).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 18 to 65 years.

Right-handed.

Diagnosis of generalized anxiety disorder (GAD) according to ICD-10 criteria (F41.1), confirmed by a psychiatrist.

GAD must be the primary diagnosis and the main reason for treatment at the time of enrollment. Current or past comorbid major depressive disorder will be identified and recorded.

Disqualifiers

Intracranial or head/neck metallic foreign bodies or implants that constitute a contraindication to TMS or MRI.

Implanted electronic devices such as a cardiac pacemaker, implantable cardioverter-defibrillator, or deep brain stimulator.

Untreated or clinically unstable thyroid dysfunction based on abnormal TSH and/or free T4 levels.

Clinically significant intracranial structural abnormalities that may affect TMS safety, neuropsychiatric presentation, or study neurophysiological measures.

Trial design

Design model

Parallel

Treatments tested in this trial

Continuous Theta Burst Stimulation of the Right Posterior Parietal Cortex
Device
Continuous theta burst stimulation (cTBS) is delivered to the right posterior parietal cortex (R-PPC), identified at the P4 location of the international 10-20 EEG system. Each session consists of 600 pulses delivered at 80% of the resting motor threshold (RMT). Participants receive two sessions per treatment day, separated by 30 ± 5-minute intervals, for a total of 10 sessions over approximately 1 week.
Continuous Theta Burst Stimulation of the Right Dorsolateral Prefrontal Cortex
Device
Continuous theta burst stimulation (cTBS) is delivered to the right dorsolateral prefrontal cortex (R-DLPFC), identified using the Beam F4 approach. Each session consists of 600 pulses delivered at 100% of the resting motor threshold (RMT). Participants receive one session per treatment day, 5 days per week for 4 weeks, for a total of 20 sessions.

Treatment groups

40 Participants

are divided into 2 treatment groups

Group A: cTBS Right Posterior Parietal CortexExperimental treatment 1 intervention

Group B: cTBS Right Dorsolateral Prefrontal CortexExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Change in Hamilton Anxiety Rating Scale (HAM-A) Total Score

The Hamilton Anxiety Rating Scale (HAM-A) is used to assess the severity of anxiety symptoms. The scale consists of 14 items, each rated from 0 to 4, yielding a total score ranging from 0 to 56, with higher scores indicating greater anxiety severity. The primary outcome is the change in HAM-A total score from baseline (T0) to the end-of-treatment assessment (T4).

Time frame