Cole, E., Gulser, M., Stimpson, K., Bentzley, B., Hawkins, J., Xiao, X., … & Williams, N. (2019). Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression (SAINT-TRD). Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation, 12(2), 402.
Background: Current treatments for depression are limited by suboptimal efficacy, delayed response, and frequent side effects. Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation treatment which is FDA-approved for treatment-resistant depression. Recent studies suggest several improvements could be made to iTBS by 1) precision targeting of the left dorsolateral prefrontal cortex (L-DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit, 2) treating with multiple sessions per day at spaced intervals and 3) applying a higher overall pulse dose of stimulation.
Objective: Examine the feasibility, tolerability, and preliminary efficacy of an accelerated, high-dose, fcMRI-guided iTBS protocol for treatment-resistant depression (TRD) termed ‘Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)’.
Methods: Thirty-one participants with TRD received open-label SAINT. Resting-state functional connectivity MRI (fcMRI) was used to individually target the region of L-DLPFC most anticorrelated with sgACC. Fifty iTBS sessions (1800 pulses per session, 50-minute inter-session interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT.
Results: Twenty-eight of 31 participants (90.32%) met criteria for remission (≤10 on the MADRS) and all 31 were remitted on measures of suicidal ideation. Neuropsychological testing demonstrated no negative cognitive side-effects. There were no seizures or other severe adverse events.
Discussion: Our highly accelerated, high-dose, iTBS protocol with fcMRI-guided targeting (SAINT) was well tolerated and safe. Efficacy was strikingly high, especially for this treatment-resistant population. Double-blinded sham-controlled trials are required to confirm the high remission rate found in this initial study.
Publication link: https://www.biorxiv.org/content/biorxiv/early/2019/05/01/581280.full.pdf