Rapid Non-Invasive Brain Stimulation for OCD (oTMS)
Phase: NA
Conditions: OCD
Sponsor: Stanford University

Clinicaltrials.gov ID 43421 
Title: Rapid Non-Invasive Brain Stimulation for OCD (oTMS) 
Update 4/22/21 
Published Results: Accelerated neuromodulation therapy for Obsessive-Compulsive Disorder. 
Williams NR, Sudheimer KD, Cole EJ, Varias AD, Goldstein-Piekarski AN, Stetz P, Lombardi A, 
Filippou-Frye M, van Roessel P, Anderson K, McCarthy EA, Wright B, Sandhu T, Menon S, Jo 
B, Koran L, Williams LM, Rodriguez CI. Brain Stimul. 2021 Mar-Apr;14(2):435-437. PubMed 
33631349. 
 
Study Protocol (see published results – citation above for further details)  
Between 7/2018 and 7/2019, eligible participants were recruited from the community by 
advertisements and referrals. Eligibility included being age 18 to 80, meeting OCD DSM-5 
criteria, with at least moderate symptoms (Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] 
score ≥ 18), and having failed ≥ one prior adequate trial (using APA Guidelines’ dose and duration 
definitions) of first-line OCD treatment (SRI or CBT). The Stanford Institutional Review Board 
approved the study, and all participants provided written informed consent. Participants who were 
already taking an SRI remained on a stable dose for ≥ 12 weeks before study entry. Exclusion 
criteria were: severe depression (Hamilton Depression Rating Scale [HDRS-17] > 20); age of OCD 
onset > 30 years; comorbid medical or psychiatric conditions making participation unsafe; or 
taking medications that increase cortical excitability, inhibit brain excitability, or create hazard 
with TMS. Subjects planning to commence CBT within 8 weeks before enrollment were also 
excluded. Independent raters administered the Y-BOCS (primary outcome measure) weekly for 4 
weeks. Response was defined a priori as a > 35% reduction in Y-BOCS score. The primary 
outcome was change in Y-BOCS score at Day 14. 
 
Before beginning the accelerated cTBSmod protocol, each participant completed a neuroimaging 
session that included a resting sequence for determining a personalized frontal pole TMS target 
and task-based fMRI elicited by the Go/No-Go task (Supplementary Material). All scans were 
acquired using a 3-tesla GE Discovery MR750 scanner with a NOVA Medical 32-channel head 
coil and a 3x accelerated multi-band (simultaneous multi-slice) imaging sequence with a repetition 
time of 2 seconds. 

 
The resting state fMRI sequence was acquired to generate each participant’s personalized right 
frontal pole TMS target (Supplementary Material). The right frontal pole subunit showing greatest 
connectivity across all the ventral striatum subunits was selected as the stimulation target in each 
participant (target generation methods and commentaries are provided elsewhere).[5, 10] 
 
Participants received 5 consecutive days of accelerated cTBSmod to the right frontal pole. Each 
cTBSmod session was comprised of 1800 pulses, delivered in a continuous train of 600 bursts. 
Each burst contained 3 pulses at 30 Hz, repeated at 6 Hz.[1] Ten sessions were applied per day 
(18,000 pulses/day, hourly) (90,000 total pulses) using a Magventure Magpro X100. Stimulation 
was delivered at 90% resting motor threshold (depth corrected). Localite Neuronavigation System 
was used to position the TMS coil over the individualized stimulation target. 
 
Statistical Analysis Plan 
Mann-Whitney nonparametric test with Y-BOCS change score as outcome was conducted to 
determine the group difference (responders vs nonresponders) in magnitude of change in left and 
right DLPFC activity, elicited during inhibitory control, from before to after treatment with the 
cTBSmod protocol. The Wilcoxon signed rank test (i.e., paired test) was used to determine within 
individual differences between left and right side of the DLPFC in cognitive control activation 
evoked by the No-Go condition of the Go/No-Go task. One participant was removed from the 
neuroimaging analysis due to excess motion.