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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
40
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 (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.
Military Hospital 175
Ho Chi Minh City, Vietnam
RECRUITINGChange 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: Baseline (T0) and 24-72 hours after the final treatment session (T4)
Change in World Health Organization Quality of Life-BREF (WHOQOL-BREF) Scores
Quality of life is assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF), which evaluates four domains: physical health, psychological health, social relationships, and environment. Each domain score is transformed to a 0-100 scale, with higher scores indicating better quality of life. Change in each domain score from baseline to the end-of-treatment assessment will be evaluated.
Time frame: Baseline (T0) and 24-72 hours after the final treatment session (T4)
Change in Pittsburgh Sleep Quality Index (PSQI) Global Score
The Pittsburgh Sleep Quality Index (PSQI) is used to assess subjective sleep quality over the previous month. It comprises seven component scores that are summed to produce a global score ranging from 0 to 21, with higher scores indicating poorer sleep quality. The outcome is the change in PSQI global score from baseline (T0) to the end-of-treatment assessment (T4).
Time frame: Baseline (T0) and 24-72 hours after the final treatment session (T4)
Change in Montreal Cognitive Assessment (MoCA) Total Score
The Montreal Cognitive Assessment (MoCA) is used to assess global cognitive function across multiple cognitive domains. The total score ranges from 0 to 30, with higher scores indicating better cognitive performance. The outcome is the change in MoCA total score from baseline (T0) to the end-of-treatment assessment (T4).
Time frame: Baseline (T0) and 24-72 hours after the final treatment session (T4)
Change in Mini-Mental State Examination (MMSE) Total Score
The Mini-Mental State Examination (MMSE) is used to assess global cognitive function. The total score ranges from 0 to 30, with higher scores indicating better cognitive performance. The outcome is the change in MMSE total score from baseline (T0) to the end-of-treatment assessment (T4).
Time frame: Baseline (T0) and 24-72 hours after the final treatment session (T4)
Incidence of Adverse Events and Serious Adverse Events
Safety and tolerability will be assessed by monitoring adverse events (AEs) and serious adverse events (SAEs) throughout the treatment period. Adverse events potentially associated with iTBS, including headache, scalp discomfort, dizziness, and other reported adverse events, will be recorded. The number and proportion of participants experiencing at least one AE or SAE will be summarized by treatment group.
Time frame: From the first treatment session through the end-of-treatment assessment (T4)
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