272. EFFECTIVENESS OF TRANSCRANIAL PULSE STIMULATION FOR MAJOR DEPRESSION: PRELIMINARY EVIDENCE FOR CLINICAL RESPONSE AND NEUROIMAGING MECHANISMS

Abstract Background Major depressive disorder (MDD) is a global disease with a high disease burden. Transcranial pulse stimulation (TPS) is a novel non-invasive brain stimulation technique utilizing shockwaves to modulate brain function. However, no randomized, double-blind, sham-controlled TPS trial has been conducted in patients with MDD. Aims & Objectives To examine the feasibility of conducting a randomized, double-blind, sham-controlled trial of TPS in patients with MDD and to investigate the preliminary clinical efficacy and neuroimaging mechanism of TPS on major depression. Method A total of 58 patients with MDD were randomized into an active group (n=29) and a sham group (n=29). TPS treatment consisted of three sessions per week for four weeks with 1000 pulses per session. The left dorsolateral prefrontal cortex (lDLPFC) was located by transforming the coordinates (x=-38, y=+44, z=+26 mm) in the MNI space to the individual T1-weighted space. During treatment, accurate positioning was achieved using real-time magnetic resonance image-guided neuronavigation. Moreover, resting-state functional magnetic resonance imaging (rs-fMRI) was measured before and after 4 weeks of treatment. The primary outcome measure assessed the feasibility of the protocol, while the secondary outcome evaluated the treatment effect on depressive symptoms as measured by the Montgomery-Asberg Depression Rating Scale (MADRS). Additionally, seed-based resting-state functional connectivity (FC) analysis was conducted to explore the changes in FC of lDLPFC following TPS. Results 93% of randomized participants completed the protocol. Mild adverse events occurred during the treatment period, including tingling, pain, numbness, headache, nausea, difficulty concentrating, redness in the skin, and sleep disturbances. A significant group*time interaction effect (p=0.014) with a significant main effect of time (p<0.001) was observed in the MADRS score. In addition, the active group showed a significantly greater reduction in MADRS score (active vs. sham: 12.86±9.23 vs. 6.77±8.64 [mean±SD], p=0.016) and a significantly higher response rate (active vs. sham: 64.3% vs. 23%, p=0.002) and remission rate (remission rate: active vs. sham: 50% vs. 23%, p=0.041) compared to the sham group. Rs-fMRI data from 51 participants with MDD were analyzed (n=26 in the active group, n=25 in the sham group). In the active group, an increase in lDLPFC-based FC to the medial prefrontal cortex (MPFC) was found after TPS (post-TPS vs. pre-TPS: t-value=5.27, cluster-level pFWE-corr=0.005, cluster size: 94 voxels, peak MNI coordinate: x=12, y=60, z=9); whereas no FC change was detected in the sham group. Discussion & Conclusions Our pilot RCT demonstrated the feasibility of conducting randomized, double-blind, sham-controlled TPS trials in patients with MDD. The preliminary results show that TPS is a promising and effective therapy for patients with MDD, and the FC between lDLPFC and MPFC was enhanced after TPS treatment. Future studies should include larger sample sizes to validate the treatment effect size and the modulation of brain circuits.