Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression (SAINT-TRD)

Abstract

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 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)'.Methods: Twenty-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.Results: Nineteen of 21 participants (90.48%) met criteria for remission (≤10 on the Montgomery-Åsberg Depression Rating Scale) immediately after SAINT. Neuropsychological testing demonstrated no negative cognitive side-effects. There were no seizures or other severe adverse events.Discussion: Our 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.

The After-Effect of Accelerated Intermittent Theta Burst Stimulation at Different Session Intervals

“…However, previous studies have focused on exploring the effects of two repeated blocks of iTBS with different intervals or single iTBS (Gamboa et al, 2011;Chung et al, 2018;Tse et al, 2018); repeated triple blocks of iTBS studies are lacking. Williams et al (2018) first stated that 10 sessions of iTBS1800 per day are an effective treatment for refractory depression; this aiTBS protocol was then named Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) (Cole et al, 2019). The present study compared the effects of triple blocks of iTBS600 (total 1,800 pulses per session) at different time intervals (0, 10, and 30 min) on motor cortical excitability in a crossover design.…”

“… Williams et al (2018) first stated that 10 sessions of iTBS1800 per day are an effective treatment for refractory depression; this aiTBS protocol was then named Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) ( Cole et al, 2019 ). The present study compared the effects of triple blocks of iTBS600 (total 1,800 pulses per session) at different time intervals (0, 10, and 30 min) on motor cortical excitability in a crossover design.…”

Funktionelle Neuroanatomie der Depression

“…Bei der tiefen Stimulation wird eine sehr große Spule eingesetzt, deren induziertes Feld im Vergleich zu den üblichen fokalen Spulen ausgedehnter ist, also den Kortex breitflächiger und tiefer stimuliert 54 , 70 . Bei einem akzelerierten Stimulationsprotokoll wird die jeweilige Stimulation mehrmals täglich appliziert 5 , 16 . Ein wahrscheinlich wesentlich effizienteres Stimulationsprotokoll, der Theta burst, wird sowohl unilateral links 11 als auch bilateral eingesetzt 66 und führt bei wesentlich kürzeren Stimulationszeiten (3–8 Minuten) zu ähnlichen klinischen Effekten.…”

“…Interessanterweise prädizierte die Ausprägung der Konnektivität zwischen dem rechten Stimulationsort und dem sugenualen zingulären Kortex den Therapieerfolg: Je stärker die Antikorrelation war, desto mehr profitierten die Patienten. Bei der zweiten Studie 16 handelte es sich um eine Hochdosisanwendung ohne Verblindung (open label), bei der 22 behandlungsresistente Patienten über 5 Tage hinweg 10-mal täglich erregend mit Theta-Burst über dem linken DLPFC behandelt wurden. Der Stimulationsort wurde über die stärkste Konnektivität (Antikorrelation) zum subkallosalen zingulärem Kortex ausgewählt.…”

Resting fMRI-guided TMS evokes subgenual anterior cingulate response in depression

“…An innovative accelerated rTMS treatment based on connectivity with the sgACC has shown high response and remission rates in two studies of treatment resistant depressed patients 9,10 .…”