Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: a systematic review and meta-analysis

Background and Aims: Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as an intervention for treating substance dependence. We aimed to assess evidence of the anti-craving and consumption-reducing effects of rTMS in patients with alcohol, nicotine and illicit drug dependence. Methods: A systematic review and meta-analysis of 26 randomized controlled trials (RCTs) published from January 2000 to October 2018 that investigated the effects of rTMS on craving and substance consumption in patients with nicotine, alcohol and illicit drug dependence (n = 748). Craving, measured using self-reported questionnaires or visual analog scale, and substance consumption, measured using self-report substance intake or number of addiction relapse cases, were considered as primary and secondary outcomes, respectively. Substance type, study design and rTMS parameters were used as the independent factors in the meta-regression. Results: Results showed that excitatory rTMS of the left dorsolateral pre-frontal cortex (DLPFC) significantly reduced craving [Hedges’ g = −0.62; 95% confidence interval (CI) = −0.89 to −0.35; P < 0.0001], compared with sham stimulation. Moreover, meta-regression revealed a significant positive association between the total number of stimulation pulses and effect size among studies using excitatory left DLPFC stimulation (P = 0.01). Effects of other rTMS protocols on craving were not significant. However, when examining substance consumption, excitatory rTMS of the left DLPFC and excitatory deep TMS (dTMS) of the bilateral DLPFC and insula revealed significant consumption-reducing effects, compared with sham stimulation. Conclusion: Excitatory repetitive transcranial magnetic stimulation of the dorsolateral pre-frontal cortex appears to have an acute effect on reducing craving and substance consumption in patients with substance dependence. The anti-craving effect may be associated with stimulation dose.