Efficacy and safety of transcranial direct current stimulation in alcohol use disorder: A randomized controlled triple‐blind trial

Abstract Background and aims Current treatment options for alcohol use disorder are limited. Transcranial direct current stimulation has been proposed as a therapeutic approach, but evidence remains scarce. This study aimed to compare active vs. sham transcranial direct current stimulation to evaluate its efficacy and safety in reducing alcohol consumption in a large sample of individuals with alcohol use disorder. Design REDSTIM is a triple‐blind, randomized, sham‐controlled trial that was conducted from October 2015 to January 2022. Participants were followed up every 4 weeks for 24 weeks. Setting Fourteen sites in France and Monaco. Participants 356 adult outpatients with alcohol use disorder were assessed for eligibility, and 337 were enrolled and randomly assigned (1:1) to receive active or sham stimulation. At baseline, the randomized participants were primarily male (60.5%) with an average age of 51.3 ± 11.3 years. Intervention and comparator Two daily stimulation sessions (anode F4, cathode F3, 2 mA) delivered over five consecutive days vs. sham stimulation. Direct currents were applied via a pair of 0.9% NaCl‐soaked surface sponge electrodes (25 cm 2 ). In the sham stimulation group, the initial ramp‐up time of 15 s (also up to 2 mA) was immediately followed by a ramp down phase of 30 seconds. Measurements The co‐primary outcomes were the change in the number of heavy drinking days (HDD) and total alcohol consumption (TAC) over the follow‐up period. Exploratory secondary outcomes included alcohol craving, clinical and biological improvements, quality‐of‐life, mood, cognitive and safety assessments. Findings Over 24 weeks of follow‐up, vs. sham, the active stimulation group reported statistically significant reductions in the number of HDD −2.45 HDD/4 weeks, 97.5% confidence interval (CI) = −4.86 to −0.05, P = 0.022. The reduction in TAC was not statistically significant (−5.96 g/day, 97.5% CI = −15.18 to 3.26, P = 0.147). The interpretation of these findings should take into account the proportion of missing data related to alcohol diary completeness and losses to follow‐up. For secondary outcomes at 24 weeks, vs. sham, craving assessments were lower in the stimulation group (−0.36 95% CI = −0.65 to −0.07, P = 0.016), as were carbohydrate deficient transferrin levels (−0.33 95% CI = −0.65 to −0.01, P = 0.045). In the active vs. sham stimulation group, 69 (41.1%) and 62 participants (36.7%) experienced one or more adverse effects, resulting in 6 dropouts. Conclusions Among adult outpatients with alcohol use disorder, active transcranial direct current stimulation resulted in a modest but sustained reduction in heavy drinking days over 24 weeks, while no statistically significant effect was observed for total alcohol consumption. The intervention was well tolerated.