Abstract
BackgroundAlcohol addiction is associated with a high disease burden, and treatment options are limited. In a proof-of-concept study, we used deep repetitive transcranial magnetic stimulation (dTMS) to target circuitry associated with the pathophysiology of alcohol addiction. We evaluated clinical outcomes and explored associated neural signatures using functional magnetic resonance imaging. MethodsThis was a double-blind, randomized, sham-controlled trial. A total of 51 recently abstinent treatment-seeking patients with alcohol use disorder (moderate to severe) were randomized to sham or active dTMS, using an H7 coil targeting midline frontocortical areas, including the medial prefrontal and anterior cingulate cortices. Treatment included 15 sessions over 3 weeks, followed by five sessions over 3 months of follow-up. Each session delivered 100 trains of 30 pulses at 10 Hz. The primary predefined outcome was reduction in percentage of heavy drinking days, obtained using timeline follow-back interviews. Secondary analyses included self-reports of craving, ethyl glucuronide in urine, and brain imaging measures. ResultsBoth craving after treatment and percentage of heavy drinking days during follow-up were significantly lower in the active versus sham control group (percentage of heavy drinking days = 2.9 ± 0.8% vs. 10.6 ± 1.9%, p = .037). Active dTMS was associated with decreased resting-state functional connectivity of the dorsal anterior cingulate cortex with the caudate nucleus and decreased connectivity of the medial prefrontal cortex to the subgenual anterior cingulate cortex. ConclusionsWe provide initial proof-of-concept for dTMS targeting midline frontocortical structures as a treatment for alcohol addiction. These data strongly support a rationale for a full-scale confirmatory multicenter trial. Therapeutic benefits of dTMS appear to be associated with persistent changes in brain network activity.
Highlights
Alcohol addiction is associated with a high disease burden, and treatment options are limited
We first established that randomization had not introduced any group differences at baseline and focused the initial analysis on the posttreatment data. This analysis found that the active group had significantly decreased connectivity between the medial PFC (mPFC) seed and a cluster in the subgenual anterior cingulate cortex (ACC) (MNI = 22, 37, 28; cluster size = 7 voxels, corrected; F1,30 = 9.19, p, .005, hp2 = 0.24) and decreased connectivity between the dorsal ACC (dACC) seed and the caudate that was nominally significant and on the threshold of cluster size required for multiple correction (MNI = 13, 16, 25; cluster size = 5; 5.6 needed for correction; F1,30 = 12.23, p, .002, hp2 = 0.29)
Double-blind, sham-controlled proof-ofconcept trial, we found that deep repetitive transcranial magnetic stimulation (dTMS) with a midline prefrontal target significantly reduced alcohol craving and heavy drinking
Summary
This was a double-blind, sham-controlled, randomized clinical trial performed at the Ben-Gurion University and the Soroka Medical Center, Be’er Sheva, Israel. Recruitment occurred between July 2016 and December 2019. The study was approved by the local Institutional Review Board (0404-15) and the Israeli Ministry of Health and was registered at ClinicalTrials.gov (NCT02691390).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
