Rakesh Gopalkumar, Adams Thomas G, Ballard Dylan H, McLouth Christopher J, Rush Craig R
Department of Psychiatry, College of Medicine, University of Kentucky, Lexington, KY.
Department of Psychiatry, School of Medicine, Yale University, New Haven, CT.
medRxiv. 2025 Mar 24:2025.03.24.25324326. doi: 10.1101/2025.03.24.25324326.
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.
迫切需要新的干预措施来治疗甲基苯丙胺使用障碍（MUD），目前尚无美国食品药品监督管理局（FDA）批准的治疗方法。先前针对MUD患者的研究表明，对左侧背外侧前额叶皮质（L. dlPFC）进行经颅磁刺激（TMS）可减少对甲基苯丙胺的渴望。theta爆发刺激（TBS），包括间歇性TBS和连续性TBS（cTBS），越来越多地用于物质使用障碍，包括MUD。先前关于MUD中TMS的综述对在MUD中实施TBS的研究进行了亚组荟萃分析。然而，这些荟萃分析纳入了参与者队列重叠的研究。鉴于此前没有使用独特参与者队列对MUD中的TBS进行荟萃分析或综述，我们检索了三个数据库（PubMed/Medline、EMBASE、谷歌学术）截至2024年9月1日的随机对照试验（RCT），比较TBS与假TBS对MUD患者线索诱导的甲基苯丙胺渴望的影响。我们对四项实施间歇性TBS的合格RCT进行了荟萃分析。结果表明，与假间歇性TBS相比，间歇性TBS在减少线索诱导的甲基苯丙胺渴望方面更有效（变化的标准化平均差[SMD]=1.04；95%置信区间[0.16, 1.92]）。我们的系统评价还纳入了另外两项没有假对照臂的RCT；其中一项研究表明，加速间歇性TBS可显著降低甲基苯丙胺渴望。未来的研究应通过测量复吸情况，检验间歇性TBS是否能影响除渴望之外的临床结局指标，如甲基苯丙胺使用情况。探索加速间歇性TBS和连续性TBS对MUD的作用并研究它们对MUD相关生物标志物的影响也很有意义。
