• Ali R Rezai, James J Mahoney, Manish Ranjan, Marc W Haut, Wanhong Zheng, Laura R Lander, James H Berry, Daniel L Farmer, Jennifer L Marton, Padma Tirumalai, Ashley Mears, Daisy G Y Thompson-Lake, Victor S Finomore, Pierre-François D'Haese, Will M Aklin, David T George, John D Corrigan, and Sally L Hodder.
• 1Departments of Neurosurgery.
• J. Neurosurg. 2024 Jan 1; 140 (1): 231239231-239.

ObjectiveThere were more than 107,000 drug overdose deaths in the US in 2021, the most ever recorded. Despite advances in behavioral and pharmacological treatments, over 50% of those receiving treatment for opioid use disorder (OUD) experience drug use recurrence (relapse). Given the prevalence of OUD and other substance use disorders (SUDs), the high rate of drug use recurrence, and the number of drug overdose deaths, novel treatment strategies are desperately needed. The objective of this study was to evaluate the safety and feasibility of deep brain stimulation (DBS) targeting the nucleus accumbens (NAc)/ventral capsule (VC) and potential impact on outcomes in individuals with treatment-refractory OUD.MethodsA prospective, open-label, single-arm study was conducted among participants with longstanding treatment-refractory OUD (along with other co-occurring SUDs) who underwent DBS in the NAc/VC. The primary study endpoint was safety; secondary/exploratory outcomes included opioid and other substance use, substance craving, and emotional symptoms throughout follow-up and 18FDG-PET neuroimaging.ResultsFour male participants were enrolled and all tolerated DBS surgery well with no serious adverse events (AEs) and no device- or stimulation-related AEs. Two participants sustained complete substance abstinence for > 1150 and > 520 days, respectively, with significant post-DBS reductions in substance craving, anxiety, and depression. One participant experienced post-DBS drug use recurrences with reduced frequency and severity. The DBS system was explanted in one participant due to noncompliance with treatment requirements and the study protocol. 18FDG-PET neuroimaging revealed increased glucose metabolism in the frontal regions for the participants with sustained abstinence only.ConclusionsDBS of the NAc/VC was safe, feasible, and can potentially reduce substance use, craving, and emotional symptoms in those with treatment-refractory OUD. A randomized, sham-controlled trial in a larger cohort of patients is being initiated.

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