Transcranial direct current stimulation combined with alcohol cue inhibitory control training reduces the risk of early alcohol relapse : a randomized placebo-controlled clinical trial

Background: Approximately half of all people with alcohol use disorder (AUD) relapse into alcohol reuse in the next few weeks after a withdrawal treatment. Brain stimulation and cognitive training represent recent forms of complementary interventions in the context of AUD. Objective: To evaluate the clinical efficacy of five sessions of 2 mA bilateral transcranial direct current stimulation (tDCS) for 20 min over the dorsolateral prefrontal cortex (DLPFC) (left cathodal/right anodal) combined with alcohol cue inhibitory control training (ICT) as part of rehabilitation. The secondary outcomes were executive functioning (e.g. response inhibition) and craving intensity, two mechanisms strongly related to abstinence. Methods: A randomized clinical trial with patients (n = 125) with severe AUD at a withdrawal treatment unit. Each patient was randomly assigned to one of four conditions, in a 2 [verum vs. sham tDCS] x 2 [alcohol cue vs. neutral ICT] factorial design. The main outcome of treatment was the abstinence rate after two weeks or more (up to one year). Results: Verum tDCS improved the abstinence rate at the 2-week follow-up compared to the sham condition, independently of the training condition (79.7% [95% CI = 69.8-89.6] vs. 60.7% [95% CI = 48.3-73.1]; p = .02). A priori contrasts analyses revealed higher abstinence rates for the verum tDCS asso-ciated with alcohol cue ICT (86.1% [31/36; 95% CI = 74.6-97.6]) than for the other three conditions (64% [57/89; 95% CI = 54-74]). These positive clinical effects on abstinence did not persist beyond two weeks after the intervention. Neither the reduction of craving nor the improvement in executive control resulted specifically from prefrontal-tDCS and ICT. Conclusions: AUD patients who received tDCS applied to DLPFC showed a significantly higher abstinence rate during the weeks following rehabilitation. When combined with alcohol specific ICT, brain stimu-lation may provide better clinical outcomes. Trial Registration: ClinicalTrials.gov number NCT03447054 https://clinicaltrials.gov/ct2/show/ NCT03447054