Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD).

Cole, E. J.; Stimpson, K. H.; Gulser, M.; Cherian, K.; Tischler, C.; Nejad, R.; Bentzley, B. S.; Pankow, H.; Choi, E.; Aaron, H.; Espil, F. M.; Pannu, J.; Xiao, X.; Duvio, D.; Solvason, H. B.; Hawkins, J.; Keller, J.; Schatzberg, A. F.; Sudheimer, K. D.; Williams, N. R.

doi:10.1101/581280

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bioRxiv · 10.1101/581280

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD).

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Abstract

BackgroundCurrent 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 that is FDA-approved for treatment-resistant depression (TRD). Recent methodological advancements suggest iTBS could be improved through 1) treating with multiple sessions per day at optimally-spaced intervals, 2) applying a higher overall pulse-dose of stimulation and 3) precision targeting of the left dorsolateral prefrontal cortex (L-DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. We examined the feasibility, tolerability, and preliminary efficacy of an accelerated, high-dose, resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for TRD termed Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT). MethodsTwenty-one participants with TRD received open-label SAINT. 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. ResultsNineteen of 21 participants (90.48%) met criteria for remission ([≤]10 on the Montgomery-[A]sberg Depression Rating Scale) immediately after SAINT. Neuropsychological testing demonstrated no negative cognitive side-effects. There were no seizures or other severe adverse events. DiscussionOur 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. Trial registrationClinicalTrials.gov NCT03240692

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Cole, E. J., Stimpson, K. H., Gulser, M., Cherian, K., Tischler, C., Nejad, R., Bentzley, B. S., Pankow, H., Choi, E., Aaron, H., Espil, F. M., Pannu, J., Xiao, X., Duvio, D., Solvason, H. B., Hawkins, J., Keller, J., Schatzberg, A. F., Sudheimer, K. D., Williams, N. R.. 2019-03-28. Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD).. https://doi.org/10.1101/581280

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