BACKGROUND: Deep brain stimulation (DBS) is an emerging and promising therapeutic approach for treatment-refractory obsessive-compulsive disorder (OCD). The most common DBS targets include the anterior limb of internal capsule (ALIC) and nucleus accumbens (NAcc). This protocol aims to explore the efficacy and safety of the combined ALIC- and NAcc-DBS for treatment-refractory OCD.
METHODS: We will recruit 64 patients with refractory OCD from six centers, randomly allocate them to active and sham-stimulation groups through a three-month double-blind phase, then enter a three-month open-label phase. In the open-label stage, both groups experience real stimulation.
METHODS: The primary outcome will be the efficacy and safety of combined ALIC- and NAcc-DBS, determined by treatment response rate between the active and sham-stimulation groups at the double-blind stage and spontaneously reported adverse events. The secondary outcomes are comparisons of change in Y-BOCS, CGI, HAMD, and HAMA scores at the third and sixth months compared to baseline between the active and sham-control groups, as well as the scores of the third month minus the sixth month between the two groups.

Deep brain stimulation (DBS) is currently used to treat addiction, with the nucleus accumbens (NAc) as one promising target. The anterior limb of the internal capsule (ALIC) is also a potential target, as it carries fiber tracts connecting the mesocorticolimbic circuits that are crucially involved in several psychiatric disorders, including addiction. Stimulating the NAc and ALIC simultaneously may have a synergistic effect against addiction.
Eight patients with a long history of heroin use and multiple relapses, despite optimal conventional treatments, were enrolled. Customized electrodes were implanted through the ALIC into the NAc, and deep brain stimulation (DBS) treatment began two weeks after surgery. The patients were followed for at least 24 months. The duration of drug-free time, severity of drug cravings, psychometric evaluations, and PET studies of glucose metabolism before and after DBS were conducted. All adverse events were recorded.
With DBS, five patients were abstinent for more than three years, two relapsed after abstaining for six months, and one was lost of follow-up at three months. The degree of cravings for drug use after DBS was reduced if the patients remained abstinent (p < 0.001). Simultaneous DBS of the NAc and ALIC also improved the quality of life, alleviated psychiatric symptoms, and increased glucose metabolism in addiction-related brain regions. Moreover, stimulation-related adverse events were few and reversible.
Simultaneous DBS of the NAc and ALIC appears to be safe, with few side effects, and may prevent long-term heroin relapse after detoxification in certain patients. (This trial was registered at ClinicalTrials.gov, NCT01274988).