Continuous Theta Burst Stimulation Improves Long-Term Outcomes in Alcohol Use Disorder by Modulating a...

Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by craving. While continuous theta burst stimulation (cTBS) shows promise for AUD, its long-term effects on drinking reduction and underlying mechanisms remain unclear. We evaluated the 12-month efficacy of right dorsolateral prefrontal cortex (DLPFC) cTBS for reducing alcohol consumption and identified associated neural and molecular mechanisms.

Fifty-five patients with alcohol dependence were randomized to receive 20 sessions of active cTBS targeting the right DLPFC or sham cTBS over 2 weeks. Clinical outcomes were evaluated through 5 follow-up assessments over a 12-month period. A functional magnetic resonance imaging cue-reactivity task was used to investigate craving-related neuroplasticity.

Compared with a sham treatment, active cTBS significantly reduced the risk of returning to baseline or higher drinking over 12 months (hazard ratio = 0.488, 95% CI [0.245-0.971]). At the conclusion of treatment, significant group × time interactions were observed for both the Alcohol Use Disorders Identification Test and subjective craving scores. We identified a craving-related network characterized by hyperconnectivity between frontoparietal and subcortical networks alongside hypoconnectivity between visual and ventral attention systems. Network weight changes correlated with immediate and long-term clinical improvements. Transcriptome association analysis revealed that this network's spatial pattern was linked to genes enriched for synaptic transmission and myelination.

This study provides evidence for the long-term clinical efficacy of cTBS in reducing drinking among individuals with AUD. The identified multiscale biomarker offers new insights into the hierarchical mechanisms by which cTBS achieves this efficacy, highlighting its potential as a circuit-based therapy for addiction.