Multiple Sessions of Transcranial Direct Current Stimulation (tDCS) Reduced Craving and Relapses for Alcohol Use: A Randomized Placebo-Controlled Trial in Alcohol Use Disorder

Abstract

Background: Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, has been studied as an adjunctive therapeutic agent for alcohol dependence. In a previous study, we showed that five consecutive sessions of tDCS applied bilaterally over the dorsolateral prefrontal cortex (dlPFC) reduced relapse to the use of alcohol in alcohol use disorder (AUD) outpatients. However, no changes on craving scores were observed. In the present study, we investigated if an extended number of sessions of the same intervention would reduce craving and relapses for alcohol use in AUD inpatients.Methods: Thus, a randomized, double-blind, sham-controlled, clinical trial with parallel arms was conducted (https://clinicaltrials.gov/ct2/show/NCT02091284). AUD patients from two private and one public clinics for treatment of drug dependence were randomly allocated to two groups: real tDCS (5 × 7 cm2, 2 mA, for 20 min, cathodal over the left dlPFC, and anodal over the right dlPFC) and sham-tDCS. Real or sham-tDCS was applied once a day, every other day, in a total of 10 sessions. Craving was monitored by a 5-item obsessive compulsive drinking scale once a week (one time before, three times during and once after brain stimulation) over about 5 weeks.Results: Craving scores progressively decreased over five measurements in both groups but were significantly reduced only in the real tDCS group after treatment. Corrected Hedges' within-group (initial and final) effect sizes of craving scores were of 0.3 for the sham-tDCS and of 1.1 for the real tDCS group. Effect size was 3-fold larger in the real tDCS group. In addition, the between-group analysis on craving score difference was nearly significant, and the effect size was 0.58, in favor for a larger effect in the real tDCS group when compared to sham-tDCS. Furthermore, in a 3-months follow-up after intervention, 72.2% of sham-tDCS group relapsed to the alcohol use whereas 72.7% of tDCS group were abstinent.Conclusions: Multiple sessions of bilateral prefrontal tDCS were well tolerated with no significant adverse events. Thus, extended repetitive bilateral tDCS over the dlPFC is a promising adjunctive clinical tool that could be used to reduce alcohol craving and relapses and facilitate alcoholism cessation.

A Randomized Trial of Combined tDCS Over Right Inferior Frontal Cortex and Cognitive Bias Modification: Null Effects on Drinking and Alcohol Approach Bias

“…To our knowledge, there have not been systematic investigations into the timing of repeated sessions and the delay between sessions for tDCS or CBM. In fact, prior studies with multiple sessions of tDCS in AUD participants have completed 4 sessions within 1 week (den Uyl et al., , , ) or every other day (Klauss et al., ). Whether intersession duration influences the efficacy of either CBM or tDCS is unknown, and if these techniques continue to show promising effects in reducing drinking, it may be valuable to investigate these timing effects.…”

“…While this study adds to 2 others that also found no significant changes in drinking, it may be possible that CBM is only effective on its own with treatment‐seeking individuals. tDCS needs further exploration to determine whether it may be effective in the treatment of AUDs; some future directions include testing different stimulation sites (e.g., medial prefrontal cortex; Hanlon et al., ), targeting alternative relevant phenotypes (e.g., craving; Klauss et al., ), and testing different phases of treatment (e.g., immediately after detox, during treatment, after treatment). For example, Hanlon and colleagues () have reported that reducing activity in the medial prefrontal cortex may be particularly useful for reducing craving, a response that is known to increase activity in this region (e.g., Schacht et al., ) among individuals with an AUD when shown alcohol‐related cues.…”

“…The precise mechanisms by which tDCS works are currently unclear, although there are some data that suggest anodal tDCS increases synchrony of neuronal firing as a result of reduced GABA (Kim et al., ) and increased glutamate activity (Clark et al., ). Prior research has shown that application of anodal tDCS over dorsolateral prefrontal cortex (DLPFC) reduces craving for alcohol (Boggio et al., ; Klauss et al., ), cigarettes (Boggio et al., ; Falcone et al., ), marijuana (Boggio et al., ), and food (Fregni et al., ). A recent treatment trial in which anodal tDCS was applied over right DLPFC (with cathode placed on left DLPFC) in alcohol‐dependent patients in a series of 10 sessions showed reduced craving and increased 3‐month abstinence in the verum tDCS group compared to the sham group (Klauss et al., ).…”

“…Prior research has shown that application of anodal tDCS over dorsolateral prefrontal cortex (DLPFC) reduces craving for alcohol (Boggio et al., ; Klauss et al., ), cigarettes (Boggio et al., ; Falcone et al., ), marijuana (Boggio et al., ), and food (Fregni et al., ). A recent treatment trial in which anodal tDCS was applied over right DLPFC (with cathode placed on left DLPFC) in alcohol‐dependent patients in a series of 10 sessions showed reduced craving and increased 3‐month abstinence in the verum tDCS group compared to the sham group (Klauss et al., ). In addition to the use of tDCS to reduce craving, this technique has also been used to enhance such cognitive abilities as response inhibition (Hsu et al., ; Jacobson et al., ) and learning (Clark et al., ; Kang and Paik, ; Reis et al., ).…”

Mindfulness‐Based Relapse Prevention and Transcranial Direct Current Stimulation to Reduce Heavy Drinking: A Double‐Blind Sham‐Controlled Randomized Trial

“…Yet, there are also negative findings. Recent studies have found no effects of active tDCS targeting the dlPFC versus sham tDCS on subjective and objective measures of alcohol craving and cue reactivity (den Uyl et al., ; Wietschorke et al., ), as well as AUD treatment outcomes (den Uyl et al., ; Klauss et al., 2018b).…”