Twice-Daily Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex Reduces Methamphetamine Craving: A Pilot Study

OBJECTIVES: Transcranial magnetic stimulation (TMS) holds potential promise as a therapeutic modality for disorders of addiction. Our previous findings indicate that high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsal–lateral prefrontal cortex (DLPFC) and low-frequency rTMS over the right DLPFC can reduce drug craving for methamphetamine. One major issue with rTMS is the duration of treatment and hence potential dropout rate. Theta burst stimulation (TBS) has been recently shown to be non-inferior relative to repetitive transcranial magnetic stimulation for major depression. Here, we aim to compare the clinical efficacy and tolerability of intermittent and continuous theta burst stimulation protocols targeting left or right dorsolateral prefrontal cortex on methamphetamine craving in abstinent-dependent subjects. METHODS: In this randomized single-blind pilot study, 83 abstinent methamphetamine-dependent subjects from a long-term residential treatment program were randomly allocated into three groups: intermittent theta burst stimulation (iTBS) over the left DLPFC (active group), continuous theta burst stimulation (cTBS) over the left DLPFC (active control group), or cTBS over the right DLPFC (active group) was administered twice daily over 5 days for a total of 10 sessions. We measured the primary outcome of cue-induced craving and secondarily sleep quality, depression, anxiety, impulsivity scores, and adverse effects. RESULTS: We show a pre- vs. postintervention effect on craving, which, on paired t tests, showed that the effect was driven by iTBS of the left DLPFC and cTBS of the right DLPFC, reducing cue-induced craving but not cTBS of the left DLPFC. We did not show the critical group-by-time interaction. The secondary outcomes of depression, anxiety, and sleep were unrelated to the improvement in craving in the left iTBS and right cTBS group. In the first two sessions, self-reported adverse effects were higher with left iTBS when compared to right cTBS. The distribution of craving change suggested greater clinical response (50% improvement) with right cTBS and a bimodal pattern of effect with left iTBS, suggesting high interindividual variable response in the latter. CONCLUSION: Accelerated twice-daily TBS appears feasible and tolerable at modulating craving and mood changes in abstinent methamphetamine dependence critically while reducing session length. We emphasize the need for a larger randomized controlled trial study with a sham control to confirm these findings and longer duration of clinically relevant follow-up. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry number, 17013610.