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

Abstract 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) tfUS to disrupt amygdalar activity. Methods: Eight 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-minute 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), Hamilton Depression Inventory (HAM-D), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI-II) were collected before and after every treatment session. Data was collected from May 2020 through December 2020. Results: All eight 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 and depression. tfUS resulted in a significant decrease in anxiety as measured by the HAM-A (z = -2.52, p < 0.01, pre-post-Δ= 7.56) and the BAI (z = -2.10, p < 0.05, pre-post-Δ = 18.0). tfUS also resulted in a significant decrease in depression as measured by the BDI-II (z = -2.38, p < 0.05, pre-post-Δ = 13.0). 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. ClinicalTrials.gov identifier: NCT04250441 Keywords: Anxiety, Focused ultrasound, Brain stimulation