Alcohol-specific inhibition training in patients with alcohol use disorder: a multi-centre, double-blind randomized clinical trial examining drinking outcome and working mechanisms.

AIMS: For the first time, to our knowledge, in a clinical sample with alcohol use disorder (AUD), this study compared the effects of two versions of alcohol-specific inhibition training (Alc-IT) on drinking outcomes and on experimental parameters assessing two possible working mechanisms: stimulus devaluation and inhibitory enhancement. DESIGN: Multi-centre, double-blind, three-arm clinical RCT with 3-, 6- and 12-month follow-up comparing standard Alc-IT, improved Alc-IT and an active control condition. SETTING: Three specialized AUD treatment centres in Switzerland. PARTICIPANTS: A total of 242 detoxified, recently abstinent patients with severe AUD (18-60 years; 29.8% female). INTERVENTION AND COMPARATOR: Both interventions [standard Alc-IT (n = 84) and improved Alc-IT (n = 79)] and the comparator [unspecific inhibition training (n = 79)] consisted of six sessions of a modified inhibitory task (Go/NoGo task) with alcohol-related and neutral stimuli. Both versions of Alc-IT required response inhibition in alcohol-related trials but differed in Go/NoGo ratios (standard: 50/50; improved: 75/25), with improved Alc-IT posing higher inhibitory demands. The control condition, an unspecific inhibition training, featured alcohol-related pictures in Go as well as NoGo trials. MEASUREMENTS: The primary outcome, percentage of days abstinent, was assessed at 3-month follow-up with a time-line follow-back interview. FINDINGS: The group receiving improved Alc-IT showed a significantly higher percentage of days abstinent at 3-month follow-up compared with the control group [γcontrol = 74.30; γimproved = 85.78; ß = 11.48, 95% confidence interval (CI) = 2.57, 20.40, P = 0.012, adjusted r2 = 0.062], while for standard Alc-IT no effect significantly different from zero was detected (γstandard = 70.95; ß = -3.35, 95% CI = -12.20, 5.50, P = 0.457, adjusted r2 = -0.04). CONCLUSIONS: Alcohol-specific inhibition training with high inhibitory demands increased days abstinent at 3-month follow-up in patients with severe alcohol use disorder. Such an improved, inhibitory-demanding, alcohol-specific inhibition training outperformed the standard version of alcohol-specific inhibition training, suggesting an inhibitory working mechanism.

Neurophysiological correlates of alcohol-specific inhibition in alcohol use disorder and its association with craving and relapse.

OBJECTIVE: This study investigates neurophysiological correlates of general and alcohol-specific inhibitory control in patients with Alcohol Use Disorder (AUD), focusing on its association with individual craving levels and with relapse at three-month follow-up. METHODS: 59 abstinent AUD patients and 20 healthy controls performed a Go/NoGo task incorporating alcohol-related and neutral stimuli during 64-channel electroencephalography (EEG) recording, yielding four event-related potentials (ERP) per participant (NoGo-Alcohol, Go-Alcohol, NoGo-Neutral, Go-Neutral). Whole-scalp randomization-based statistics assessed effects of the factors group (patients/controls or relapsers/abstainers), craving level, response type (NoGo/Go) and picture type (alcohol/neutral) on topography and signal strength of the ERP components N2 and P3. RESULTS: No differences on group level were observed between patients and controls. However, analyses incorporating individual craving indicated that the topographic difference between alcohol-related and neutral NoGo-N2 components increased with craving. Moreover, topographic differences in the alcohol-related and neutral NoGo-P3 component allowed for differentiation between relapsers and abstainers. CONCLUSIONS: In alcohol-related contexts, the response inhibition conflict reflected in the NoGo-N2 seems enhanced in patients with high craving. The inhibition-sensitive NoGo-P3 varies in relapsers but not in abstainers between neutral and alcohol-related contexts. SIGNIFICANCE: In AUD patients, neurophysiological correlates of inhibition vary with alcohol-related contexts and craving, and might be indicative of relapse risk.

The Neurophysiology of Implicit Alcohol Associations in Recently Abstinent Patients With Alcohol Use Disorder: An Event-Related Potential Study Considering Gender Effects.

BACKGROUND: Neuroscientific models of alcohol use disorders (AUDs) postulate an imbalance between automatic, implicit, and controlled (conscious) processes. Implicit associations towards alcohol indicate the automatically attributed appeal of alcohol-related stimuli. First, behavioral studies indicate that negative alcohol associations are less pronounced in patients compared to controls, but potential neurophysiological differences remain unexplored. This study investigates neurophysiological correlates of implicit alcohol associations in recently abstinent patients with AUD for the first time, including possible gender effects. METHODS: A total of 62 patients (40 males and 22 females) and 21 controls performed an alcohol valence Implicit Association Test, combining alcohol-related pictures with positive (incongruent condition) or negative (congruent condition) words, while brain activity was recorded using 64-channel electroencephalography. Event-related potentials (ERPs) for alcohol-negative and alcohol-positive trials were computed. Microstate analyses investigated the effects of group (patients, controls) and condition (incongruent, congruent); furthermore, possible gender effects in patients were analyzed. Significant effects were localized with standardized low-resolution brain electromagnetic topography analysis. RESULTS: Although no behavioral group differences were found, ERPs of patients and controls were characterized by distinct microstates from 320 ms onwards. ERPs between conditions differed only in patients with higher signal strength during incongruent trials. Around 600 ms, controls displayed higher signal strength than patients. A gender effect mirrored this pattern with enhanced signal strength in females as opposed to male patients. Around 690 ms, a group-by-valence interaction indicated enhanced signal strength in congruent compared to incongruent trials, which was more pronounced in controls. CONCLUSIONS: For patients with AUD, the pattern, timing, and source localization of effects suggest greater effort regarding semantic and self-relevant integration around 400 ms during incongruent trials and attenuated emotional processing during the late positive potential timeframe. Interestingly, this emotional attenuation seemed reduced in female patients, thus corroborating the importance of gender-sensitive research and potential treatment of AUD.

New pharmacological approaches for the treatment of alcoholism.

Pharmacological relapse prevention in alcoholism is a rather new clinical field with few drugs being available. Acamprosate, acting predominantly via glutamatergic pathways, and the opioid receptor antagonist naltrexone, were both shown to be efficient in improving rates for continuous abstinence, and not relapsing to heavy drinking in a number of clinical trials and meta-analyses. There are conflicting data on both drugs, especially for acamprosate, according to some recent US studies. However, overall, the evidence is good. Both drugs are approved in most European countries and the US. Efficacy data for disulfiram are mixed; it is a second-line medication compared with other drugs, and is probably most effective when used in a supervised setting. Recently, anticonvulsants including carbamazepine and topiramate have been discussed as possible anti-craving drugs, but there is still limited evidence for their efficacy. Although there is a significant comorbidity for alcoholism with affective disorder, anxiety and schizophrenia, relatively few controlled clinical trials have been performed in this area. Tricyclics have been found to be more effective than serotonin reuptake inhibitors in improving depressive symptoms in these patients.