Background: Transcranial Magnetic, Electrical, and Focused-Ultrasound Stimulation (TMS/tES/tFUS) are major noninvasive brain stimulation (NIBS) techniques used to treat various psychiatric disorders, including substance use disorders (SUDs). Although NIBS with varying stimulation parameters shows promising effects on drug-related behaviors such as craving and consumption/relapse, the question of which protocol is most effective remains unresolved. Method: To address this gap, we conducted a living systematic review and meta-analysis to quantify the effects of TMS/tES/tFUS on SUD. Controlled trials of TMS/tES/tFUS for all types of SUD were selected up to January 1, 2024. Findings: The final systematic review included 208 trials (121 TMS, 86 tES, 1 tFUS), with 116 randomized sham-controlled trials (59 TMS, 57 tES) eligible for meta-analysis based on low risk of bias. Data from 5, 106 participants in active and 4, 914 in sham groups were analyzed. TMS showed medium effects on craving (g = 0. 52, 95% CI: 0. 29-0. 75, p < 0. 001, I² = 89. 36) and consumption (g = 0. 41, CI: 0. 26-0. 56, p < 0. 001, I² = 61. 56). tES showed a medium effect on craving (g = 0. 40, CI: 0. 25-0. 55, p < 0. 001, I² = 60. 69) and a small effect on consumption (g = 0. 27, CI: 0. 15-0. 38, p = 0. 013, I² = 22. 67). Among the 36 different protocols examined, subgroup analyses identified the strongest effect for reducing both craving and consumption with high-frequency deep TMS using the H4 coil (single study) (g = 3. 92 and 1. 12, respectively, p < 0. 001), with a maximum electric field over the frontopolar cortex. This effect was followed by high-frequency rTMS over the left DLPFC (g = 0. 66 and 0. 52, respectively, p < 0. 05), as well as bilateral anodal-right cathodal-left (g = 0. 49 and 0. 42, respectively, p < 0. 0001) and anodal-left cathodal-right (g = 0. 38 and 0. 31, respectively, p < 0. 05) tES with direct current (tDCS) over the DLPFC, with maximum electric field on the frontopolar cortex. Interpretation: Our results provide evidence that TMS and tES stimulation over frontopolar and DLPFC regions produce medium to large effect sizes in reducing drug craving and consumption/relapse in SUD. While requiring further replication in future studies, these findings highlight the promise of these interventions.
Soleimani et al. (Sun,) studied this question.
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