Efficacy of intermittent theta-burst stimulation for substance use disorders: a systematic review and meta-analysis of randomized sham-controlled trials.

OBJECTIVE: To evaluate the efficacy of intermittent theta-burst stimulation (iTBS) for substance use disorders (SUDs), with craving reduction as the primary outcome and abstinence as the secondary outcome, and to examine whether treatment effects differed by substance type. METHODS: PubMed, Embase, the Cochrane Library, Web of Science, and PEDro were searched from inception to March 17, 2026 for randomized sham-controlled trials of prefrontal iTBS in individuals with SUDs. Standardized mean differences (SMDs) were calculated for craving outcomes and odds ratios (ORs) for abstinence. Random-effects models, substance-specific subgroup analyses, and leave-one-out sensitivity analyses were used as appropriate. RESULTS: Nine randomized sham-controlled trials involving 556 participants were included. Eight trials (n = 512) contributed continuous craving data. Active iTBS was associated with a reduction in craving relative to sham stimulation (SMD = -0.65, 95% CI -1.08 to -0.21; p = 0.003), although heterogeneity was substantial (I 2 = 81%). Subgroup analyses showed a larger effect in methamphetamine use disorder (five trials, n = 311; SMD = -1.03, 95% CI -1.29 to -0.77; I 2 = 11%) and no detectable effect in nicotine use disorder (three trials, n = 201; SMD = 0.01, 95% CI -0.28 to 0.30; I 2 = 3%). Three trials involving nicotine or alcohol use disorder contributed abstinence data; the pooled estimate favored active iTBS (OR = 2.19, 95% CI 1.09 to 4.39), but the evidence base was small and follow-up was short. CONCLUSION: Current evidence suggests that prefrontal iTBS may reduce craving in methamphetamine use disorder, but the overall evidence remains substance-specific and should not be interpreted as demonstrating efficacy across all SUDs. No benefit was detected for nicotine craving. The preliminary abstinence finding requires confirmation in larger trials with longer follow-up before conclusions can be drawn regarding sustained abstinence or relapse prevention. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD420261363708.