Deep brain stimulation of the nucleus accumbens for alcohol use disorder
In recent years, DBS of the nucleus accumbens has been explored as a potential treatment for alcohol use disorder (AUD), also known as alcoholism. The idea is that electrical stimulation of this region may help to regulate the activity of the brain circuits involved in addiction, and thereby reduce the compulsions and cravings associated with alcohol dependence.
DBS of NA in animals reduced addictive behavior to alcohol, cocaine, and other narcotics significantly. The accidental observation that DBS of NA for psychiatric illnesses induced relief from addiction to alcohol and smoking has encouraged further research of late 1).
However, at this time, DBS of the nucleus accumbens for alcohol use disorder is still considered an experimental treatment, and more research is needed to determine its safety and efficacy. Currently, there are only a limited number of studies examining the use of DBS in this context, and the results have been mixed, with some studies showing promising results, while others have not.
It’s important to note that DBS is a highly invasive procedure, and it should only be considered as a last resort after other treatments have failed. A stronger therapeutic rationale based on solid physio-pathological evidence and accurate estimates of efficacy, are still required to achieve further therapeutic success and expand clinical use 2).
Bach et al. report a double-blind randomized controlled trial comparing active DBS (“DBS-EARLY ON”) against sham stimulation (“DBS-LATE ON”) over 6 months in n = 12 alcohol use disorders (AUD) patients. This 6-month blinded phase was followed by a 12-month unblinded period in which all patients received active DBS. Continuous abstinence (primary outcome), alcohol use, alcohol craving, depression, anxiety, anhedonia and quality of life served as outcome parameters. The primary intention-to-treat analysis, comparing continuous abstinence between treatment groups, did not yield statistically significant results, most likely due to the restricted number of participants. In light of the resulting limited statistical power, there is the question of whether DBS effects on secondary outcomes can nonetheless be interpreted as indicative of a therapeutic effect. Analyses of secondary outcomes provide evidence for this, demonstrating a significantly higher proportion of abstinent days, lower alcohol craving, and anhedonia in the DBS-EARLY ON group 6 months after randomization. Exploratory responder analyses indicated that patients with high baseline alcohol cravings, depressiveness, and anhedonia responded to DBS. The results of this first randomized controlled trial are suggestive of the beneficial effects of DBS in treatment-resistant AUD and encourage replication in larger samples 3).
Six patients with severe, refractory AUD underwent NAc-DBS. Safety metrics and clinical outcomes were recorded. Positron emission tomography (FDG-PET) was used to measure glucose metabolism in the NAc at baseline and 6 months. Functional magnetic resonance imaging (fMRI) was used to characterize postoperative changes in NAc functional connectivity to the rest of the brain, as well as NAc and dorsal striatal reactivity to alcoholic visual cues. This study was registered with ClinicalTrials.gov, NCT03660124. All patients experienced a reduction in cravings. There was a significant reduction in alcohol consumption, alcohol-related compulsivity, and anxiety at 12 months. There was no significant change in depression. FDG-PET analysis demonstrated reduced NAc metabolism by 6 months, which correlated with improvements in compulsive drinking behaviors. Clinical improvement correlated with reduced functional connectivity between the NAc and the visual association cortex. Active DBS was associated with reduced activation of the dorsal striatum during passive viewing of alcohol-containing pictures. NAc-DBS is feasible and safe in patients with severe, otherwise refractory AUD. It is associated with a reduction in cravings and addictive behavior. A potential mechanism underlying this process is a down-regulation of the NAc, a disruption of its functional connectivity to the visual association cortex, and interference of cue-elicited dorsal striatum reactivity. Trial Registration NCT03660124 ( www.clinicaltrials.gov). 4)