Theta Burst Stimulation in Patients With Methamphetamine Use Disorder: A Meta-Analysis and Systematic Review

Novel interventions are urgently needed to treat methamphetamine use disorder (MUD), for which there are no FDA-approved treatments. Previous studies in patients with MUD suggest transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (L. dlPFC) decreases craving for methamphetamine. Theta burst stimulation (TBS), which includes intermittent TBS and continuous TBS (cTBS), is increasingly being used for substance use disorders, including MUD. Previous reviews of TMS in MUD performed sub-group meta-analyses of studies that delivered TBS in MUD. However, these meta-analyses included studies with overlapping participant cohorts. Given the absence of prior meta-analyses or reviews examining TBS in MUD using unique participant cohorts, we reviewed randomized controlled trials (RCTs) from three databases (PubMed/Medline, EMBASE, Google Scholar) until September 1, 2024, comparing the impact of TBS versus sham TBS on cue-induced methamphetamine cravings 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 cravings than sham iTBS (standardized mean difference [SMD] in change = 1.04; 95% CI [0.16, 1.92]). Our systematic review included two additional RCTs that did not have sham comparator arms; one of these demonstrated a significant reduction in methamphetamine craving with accelerated iTBS. Future studies should examine if iTBS can impact clinical outcome measures other than craving, such as methamphetamine use, by measuring return to drug use. It is also pertinent to explore accelerated iTBS and cTBS for MUD and study their effects on relevant biomarkers for MUD.