A pilot study of low-intensity focused ultrasound for treatment-resistant generalized anxiety disorder.

Objective: This study intended to evaluate a possible therapeutic effect among patients with treatment-refractory generalized anxiety disorder (trGAD) by using transcranial focused ultrasound (tfUS) to modulate amygdalar activity.

Methods: Twenty-five participants with severe trGAD as outlined in the DSM-V were recruited from Los Angeles neurology and psychiatry clinics. All participants completed eight weekly 10-min tfUS sessions targeting the right amygdala. Functional and structural neuroimaging were used to navigate individual targets. Outcome measures including the Hamilton Anxiety Inventory (HAM-A, primary outcome) and Beck Anxiety Inventory (BAI) were collected at baseline and protocol completion. Upon study completion, participants were asked to report perceived change in clinical status using the Patient Global Impression - Improvement (PGI-I) scale. Data was collected from May 2020 through January 2023.

Results: All participants were able to tolerate treatment without notable side effects. No adverse events were reported. A Wilcoxon Signed-Rank Test was conducted to compare pre- and post-tfUS measures of anxiety. tfUS resulted in a significant decrease in anxiety as measured by the HAM-A (W = -3.69, p < 0.001, pre-post-Δ = -12.64 ± 12.51) and the BAI (W = -3.94, p < 0.001, pre-post-Δ = -12.88 ± 10.42). Sixteen (16) of twenty-five (25) total participants indicated clinically significant benefit on PGI-I scores at completion.

Conclusion: This study provides preliminary evidence supporting the safety and efficacy of tfUS as a clinical intervention. These results warrant further investigation of tfUS as a therapeutic intervention for anxiety and other psychiatric and neurological disorders.

Gov Identifier: NCT04250441.