Efficacy of transcranial direct current stimulation (tDCS) in reducing consumption in patients with alcohol use disorders: study protocol for a randomized controlled trial.
ABSTRACT: Approximately 15 million persons in the European Union and 10 million persons in the USA are alcohol-dependent. The global burden of disease and injury attributable to alcohol is considerable: worldwide, approximately one in 25 deaths in 2004 was caused by alcohol. At the same time, alcohol use disorders remain seriously undertreated. In this context, alternative or adjunctive therapies such as brain stimulation may play a prominent role. The early results of studies using transcranial direct current stimulation found that stimulations delivered to the dorsolateral prefrontal cortex result in a significant reduction of craving and an improvement of the decision-making processes in various additive disorders. We, therefore, hypothesize that transcranial direct current stimulation can lead to a decrease in alcohol consumption in patients suffering from alcohol use disorders.We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial, to evaluate the efficacy of transcranial direct current stimulation on alcohol reduction in patients with an alcohol use disorder. The study will be conducted in 14 centers in France and Monaco. Altogether, 340 subjects over 18 years of age and diagnosed with an alcohol use disorder will be randomized to receive five consecutive twice-daily sessions of either active or placebo transcranial direct current stimulation. One session consists in delivering a current flow continuously (anode F4; cathode F3) twice for 13 minutes, with treatments separated by a rest interval of 20 min. Efficacy will be evaluated using the change from baseline (alcohol consumption during the 4 weeks before randomization) to 24 weeks in the total alcohol consumption and number of heavy drinking days. Secondary outcome measures will include alcohol craving, clinical and biological improvements, and the effects on mood and quality of life, as well as cognitive and safety assessments, and, for smokers, an assessment of the effects of transcranial direct current stimulation on tobacco consumption.Several studies have reported a beneficial effect of transcranial direct current stimulation on substance use disorders by reducing craving, impulsivity, and risk-taking behavior, and suggest that transcranial direct current stimulation may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm the hypothesis. Results from this large randomized controlled trial will give a better overview of the therapeutic potential of transcranial direct current stimulation in alcohol use disorders.Clinical Trials Gov, NCT02505126 (registration date: July 15 2015).
Project description:Transcranial direct current stimulation over the dorsolateral prefrontal cortex has been shown to be clinically useful in the treatment of drug addiction.We conducted a double-blind randomized clinical trial aiming to assess the effects of bilateral dorsolateral prefrontal cortex transcranial direct current stimulation (left cathodal/right anodal) on crack-cocaine addiction. We defined craving as the primary outcome, and other clinical measurements, including depressive and anxiety symptoms, and quality of life, as secondary outcomes. Seventeen male crack-cocaine users (mean age 30.4 ± 9.8 SD) were randomized to receive 5 sessions of active transcranial direct current stimulation (2 mA, 35 cm(2), for 20 minutes), every other day, and 19 males (mean age 30.3 ± 8.4 SD) to receive sham-transcranial direct current stimulation (placebo) as control group.Craving scores were significantly reduced in the transcranial direct current stimulation group after treatment when compared with sham-transcranial direct current stimulation (P = .028) and baseline values (P = .003), and decreased linearly over 4 weeks (before, during, and after treatment) in the transcranial direct current stimulation group only (P = .047). Changes of anxiety scores towards increase in the sham-transcranial direct current stimulation and decrease in the transcranial direct current stimulation group (P = .03), and of the overall perception of quality of life (P = .031) and of health (P = .048) towards decrease in the sham-transcranial direct current stimulation group and increase in the transcranial direct current stimulation group differed significantly between groups.Repetitive bilateral transcranial direct current stimulation over the dorsolateral prefrontal cortex reduced craving for crack-cocaine use, decreased anxiety, and improved quality of life. We hypothesize that transcranial direct current stimulation effects may be associated with increased prefrontal processing and regulation of craving behavior.
Project description:BACKGROUND:Deriving novel treatments for alcohol use disorders (AUDs) is of critical importance, as existing treatments are only modestly effective for reducing drinking. Two promising strategies for treating AUDs include cognitive bias modification (CBM) and transcranial direct current stimulation (tDCS). While each strategy has shown positive results in reducing drinking or alcohol-related constructs (e.g., craving), initial tests of the combination of CBM and tDCS have shown mixed results. The present study investigated the degree to which combining CBM and tDCS (2.0 mA anodal current over F10) could reduce alcohol approach biases and alcohol consumption. METHODS:Seventy-nine at-risk drinkers were randomized to 1 of 4 conditions in a 2 × 2 factorial design: verum CBM/verum tDCS, verum CBM/sham tDCS, sham CBM/verum tDCS, or sham CBM/sham tDCS. Participants completed a baseline assessment of alcohol approach bias and drinking quantity/frequency (i.e., drinks per drinking day [DDD] and percent heavy drinking days [PHDD]), 4 sessions of combined CBM and tDCS, and follow-up assessments of approach bias and alcohol consumption. RESULTS:Results indicated that while participants did demonstrate significant alcohol approach biases at baseline, neither CBM, tDCS, nor the interaction reduced the bias at the follow-up. In addition, there was evidence of a trend toward reducing DDD from baseline to the 1-week/1-month follow-ups, but there was no significant effect of the intervention on either DDD or PHDD. CONCLUSIONS:These results partially replicated null results presented in similar CBM/tDCS trials and suggest that this combination, at least with anodal stimulation over dorsolateral or inferior frontal sites, may have limited utility to reduce drinking.
Project description:Alcohol use disorders remain one of the leading causes of mortality and morbidity across the world, yet despite this impact, there are few treatment options for patients suffering from these disorders. To this end, non-invasive brain stimulation, most commonly utilizing technologies including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), has recently emerged as promising potential treatments for alcohol use disorders. Enthusiasm for these interventions is fueled by their non-invasive nature, generally favorable safety profile, and ability to target and modulate brain regions implicated in substance use disorders. In this paper, we describe the underlying principles behind these commonly used stimulation technologies, summarize existing experiments and randomized controlled trials, and provide an integrative summary with suggestions for future areas of research. Currently available data generally supports the use of non-invasive brain stimulation as a near-term treatment for alcohol use disorder, with important caveats regarding the use of stimulation in this patient population.
Project description: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.
Project description:Modulation of dorsolateral prefrontal cortex (DLPFC) activity using non-invasive brain stimulation has been shown to reduce food craving as well as food consumption. Using a preregistered design, we examined whether bilateral transcranial direct current stimulation (tDCS) of the DLPFC could reduce food craving and consumption in healthy participants when administered alongside the cognitive target of inhibitory control training. Participants (N = 172) received either active or sham tDCS (2 mA; anode F4, cathode F3) while completing a food-related Go/No-Go task. State food craving, ad-lib food consumption and response inhibition were evaluated. Compared with sham stimulation, we found no evidence for an effect of active tDCS on any of these outcome measures in a predominantly female sample. Our findings raise doubts about the effectiveness of single-session tDCS on food craving and consumption. Consideration of individual differences, improvements in tDCS protocols and multi-session testing are discussed.
Project description:Impaired cognitive-motivational functioning is present in many psychiatric disorders, including alcohol use disorder (AUD). Emotion regulation is a key intermediate factor, relating to the (cognitive) regulation of emotional and motivational states, such as in regulation of craving or negative emotions that may lead to relapse in alcohol use. These cognitive-motivational functions, including emotion regulation, are a target in cognitive behavioral therapy and may possibly be improved by neurostimulation techniques. The present between-subjects, single-blind study assesses the effects of sham-controlled high-frequency neuronavigated repetitive transcranial magnetic stimulation (10 Hz) of the right dorsolateral prefrontal cortex (dlPFC) on several aspects relevant for emotion regulation (emotion processing and reappraisal abilities) and related brain activity, as well as self-reported craving in a sample of alcohol use disorder patients (AUD; n = 39) and healthy controls (HC; n = 36). During the emotion reappraisal task, participants were instructed to either attend or reappraise their emotions related to the negative, positive, neutral, and alcohol-related images, after which they rated their experienced emotions. We found that repetitive transcranial magnetic stimulation (rTMS) reduces self-reported experienced emotions in response to positive and negative images in AUD patients, whereas experienced emotions were increased in response to neutral and positive images in HCs. In the functional magnetic resonance imaging (fMRI) analyses, we found that rTMS reduces right dlPFC activity during appraisal of affective images relative to sham stimulation only in AUD patients. We could not confirm our hypotheses regarding the effect of rTMS craving levels, or on reappraisal related brain function, since no significant effects of rTMS on craving or reappraisal related brain function were found. These findings imply that rTMS can reduce the emotional impact of images as reflected in blood oxygenation level-dependent (BOLD) response, especially in AUD patients. Future studies should replicate and expand the current study, for instance, by assessing the effect of multiple stimulation sessions on both explicit and implicit emotion regulation paradigms and craving, and assess the effect of rTMS within subgroups with specific addiction-relevant image preferences. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02557815.
Project description:INTRODUCTION:The effectiveness of repetitive transcranial Direct Current Stimulation (tDCS) on reducing smoking behaviour has been studied with mixed results. Smoking behaviour is influenced by affect and context, therefore we choose to use mobile ecological momentary assessments (EMA) to measure changes in smoking behaviour after tDCS. METHODS:In a randomized, placebo-controlled, between subject study, we applied tDCS bilaterally with the anodal electrode targeting the right DLPFC (https://clinicaltrials.gov/ct2/show/NCT03027687). Smokers were allocated to six sessions of either active tDCS (n = 35) or sham tDCS (n = 36) and received two sessions on three different days in one week. They were asked to keep track of their daily cigarette consumption, craving and affect in an application on their mobile phones for three months starting one week before the first tDCS session. RESULTS:Number of smoked cigarettes a day progressively decreased up to one week after the last tDCS session in both conditions. Active treatment had no additional effect on cigarette consumption, craving and affect. CONCLUSIONS:In this exploratory study, repetitive bilateral tDCS over the DLPFC had no effect on daily smoking behaviour. Future research needs to investigate how motivation to quit smoking and the number of tDCS sessions affect the efficacy of repetitive tDCS.
Project description:Background:Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation technique which has a treatment potential for alcohol use disorder. Intermittent theta burst stimulation (iTBS) is a new rTMS technique which is shorter in duration and thus with better tolerability and shows similar efficacy as rTMS for the treatment of depression. The effect of iTBS on reducing craving in alcohol use disorder patients requires further investigation. Methods:A randomized, controlled, single-blind, multicenter study with 60 alcohol use disorder patients randomized (2:1) to the iTBS group or the control group (sham iTBS). The stimulation target will be identical in the left dorsolateral prefrontal cortex (DLPFC). Baseline evaluations will be occurred before the intervention, after the intervention immediately, and 1 and 3 months after the intervention. The primary outcome of the study will be decrease of visual analogue scale (VAS) scores from baseline to the end of treatment. Discussion:This study is a randomized controlled trial to investigate the efficacy of left DLPFC iTBS in a population of alcohol use disorder patients, compared with sham iTBS. If it is effective for alcohol use disorder, it may provide a potential treatment which is tolerable, accessible, and clinical useful. Cinical Trial Registration:This study is registered in the ClinicalTrials with trial number NCT03932149. Registered 17 April 2019.
Project description:Recent studies have shown that transcranial direct current stimulation (tDCS) may reduce craving and smoking. However, little is known regarding brain correlates of these behavioral changes. We aimed to evaluate whether 10 sessions of tDCS modulate cigarette consumption, craving and brain reactivity to smoking cues in subjects with tobacco use disorder (TUD). In a double blind parallel-arms study, 29 subjects with TUD who wished to quit smoking were randomly assigned to receive 10 sessions of either active or sham tDCS applied with the anode over the right dorsolateral prefrontal cortex (DLPFC) and a large cathode over the left occipital region. As compared to sham, active tDCS significantly reduced smoking craving and increased brain reactivity to smoking-cues within the right posterior cingulate, as measured with a functional magnetic resonance imaging event-related paradigm. However, we failed to find a significant difference between active and sham groups regarding the self-reported number of cigarettes smoked and the exhaled carbon monoxide during one month. These findings suggested that 10 sessions of tDCS over the right DLPFC may reduce craving by modulating activity within the resisting-to-smoke network but might not be significantly more effective than sham to decrease cigarette consumption.
Project description:Research has demonstrated the positive association between alcohol craving and alcohol use and has identified craving as a central component of alcohol use disorders (AUD). Despite potential clinical implications, few studies have examined the relationship between craving and alcohol use in individuals with AUD and common psychiatric comorbidities or explored possible moderators of the craving-alcohol use relationship. The current study used daily monitoring data to: 1) replicate previous findings detecting a positive relationship between craving and alcohol use in individuals with AUD and co-occurring posttraumatic stress disorder (PTSD) and 2) extend these findings by examining the influence of initial change motivation on the craving-use relationship and within-day associations among craving, efforts to control craving, and alcohol consumption. Participants were 84 individuals with alcohol dependence and PTSD enrolled in an intervention study. Generalized estimating equations using pre-treatment baseline daily data revealed significant main effects for craving, craving control, and motivation to change alcohol use. Daily craving was positively related to alcohol use. Greater change motivation and craving control (i.e., efforts to resist craving, avoidance of thoughts and feelings related to craving) were negatively related to alcohol use. A significant interaction was detected between baseline change motivation and daily craving indicating that the association between craving and alcohol use was significantly stronger for those with low baseline change motivation. A significant interaction was also detected between craving control and daily craving, suggesting that participants were more likely to consume alcohol when experiencing high levels of craving if they reported low levels of craving control. Findings bolster the idea that efforts to prevent or ameliorate craving are critical to treatment success for individuals with AUD and PTSD who are seeking to reduce or quit drinking.