Theta Burst Stimulation as a tool to decrease drinking in treatment-seeking alcohol users: study protocol for a randomized, double-blind, sham-controlled clinical trial.

BACKGROUND

Alcohol use disorder (AUD) remains a prevalent and challenging condition, with current behavioral and pharmaceutical treatments yielding limited success and high relapse rates. Non-invasive neuromodulation techniques, such as transcranial magnetic stimulation (TMS), offer promising therapeutic alternatives. TMS has demonstrated efficacy in modulating brain circuits associated with the limbic system and cognitive control, both critical in AUD pathology. While the dorsolateral prefrontal cortex (DLPFC) and medial prefrontal cortex (MPFC) have been identified as potential TMS targets, no studies have evaluated both sites against a sham condition in a single trial. This randomized, double-blind, sham-controlled clinical trial addresses this gap by evaluating the efficacy of multi-session intermittent theta burst stimulation (iTBS) applied to either the DLPFC or MPFC in reducing alcohol consumption, alcohol craving, and brain reactivity to alcohol cues.

METHODS

One hundred and eighty individuals with AUD will be randomized to receive real iTBS to the MPFC, real iTBS to the DLPFC, or sham iTBS. Participants will complete 30 treatment sessions, administered in 15 daily sessions spread over 3 to 6 weeks, with pre- and post-treatment MRI scans and 3 months of follow-up.

DISCUSSION: By evaluating two cortical targets and leveraging rigorous methodologies, this trial aims to generate insights that could inform future studies optimizing TMS for AUD treatment. Findings will contribute to developing standardized TMS protocols, with the potential to enhance treatment efficacy and support FDA approval, advancing TMS as an intervention for AUD.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04154111. Registered on November 6, 2019.