Discussion
death, anhedonia, anxiety, depressive, depressed, depression, disability
ADVERSE EVENTS
We present the first double-blind RCT investigating the effects of DBS on abstinence and alcohol use in AUD patients. The primary intention-to-treat analysis suggested an abstinence-promoting effect of DBS. However, the results were not statistically significant, most likely due to limited power resulting from the small sample size and the categorial primary outcome. Descriptively, the observed HR of 0.73 would translate to a NNT of 9.6, which – in the light of the NNTs observed for other relapse-preventing treatments and the sample of treatment resistant patients – is suggestive of a potential effect of DBS in AUD [In addition, we observed alcohol craving – a hallmark symptom of AUD that can act as a trigger for alcohol use – to be significantly reduced in the DBS-EARLY ON group after 6 months [Our responder analyses also indicated that responders to NAc DBS are those with higher depressiveness, anxiety and anhedonia scores at baseline. NAc DBS resulted in significantly lower anhedonia scores in the DBS-EARLY ON group versus DBS-LATE ON group. It is conceivable that the effects of DBS on alcohol use are also mediated in part by its positive impact on anhedonia, a common symptom in depression and anxiety, as well as in addiction. The positive effect of NAc DBS on anhedonia might also – at least in part – explain the observed positive effects on alcohol use during the open-label phase of the trial, when alcohol craving (OCDS and AUQ) did not show significant decreases, while alcohol use and anhedonia were attenuated. This finding is interesting in several ways: The NAc is considered a key brain region for regulating behaviors related not only to addiction, but also to depression. Previous studies in depressed patients reported significant effects of NAc DBS on depressive symptoms, including anhedonia [Regarding the safety of DBS, we did not observe any adverse events or serious adverse events resulting in lasting disability or death over the 18-month trial period, and most AEs were mild to moderate. This is in line with previous research on DBS [