Theta burst stimulation (TBS) in methamphetamine use disorder: a meta-analysis and systematic review

Methamphetamine use disorder (MUD) currently lacks FDA-approved treatments. Previous studies involving transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (L.dlPFC) have shown promise in TMS's effectiveness at decreasing craving for methamphetamine. Theta burst stimulation (TBS), which includes intermittent (iTBS) and continuous (cTBS) protocols, is increasingly being used for substance use disorders, including MUD. Previous reviews of TMS in MUD performed subgroup meta-analyses of studies that delivered TBS in MUD. However, these meta-analyses included studies with overlapping participant cohorts, limiting their validity. To address this limitation, we reviewed randomized controlled trials (RCTs) using unique patient cohorts from PubMed/Medline, EMBASE, and Google Scholar until September 1, 2024, comparing the impact of TBS versus sham on cue-induced methamphetamine craving in patients with MUD. We performed a meta-analysis with four eligible RCTs that delivered iTBS. Results suggest iTBS was more effective in reducing cue-induced methamphetamine craving than sham iTBS (standardized mean difference [SMD] in change = 1.04; 95% CI [0.16, 1.92]). Two additional RCTs without sham control arms were reviewed, and one demonstrated a significant reduction in craving following accelerated iTBS. Future studies should examine whether neuroimaging-targeted iTBS can impact outcome measures other than craving, such as methamphetamine use, by measuring return to use. Exploring accelerated iTBS and cTBS for MUD, targeting alternative cortical sites such as the frontal pole, and studying their effects on relevant MUD biomarkers is also pertinent. This review demonstrates the effectiveness of TBS for MUD, emphasizing its potential to advance treatment options for MUD.