Deep Brain Stimulation of the Nucleus Accumbens and Anterior Limb of the Internal Capsule in the Treatment of Refractory Schizophrenia

Summary

Schizophrenia is a lifelong psychiatric disorder with a prevalence rate of 0.559% and a lifetime prevalence rate of 0.588% among Chinese adults. It often causes social dysfunction and psychiatric disability, shortening patients' life expectancy by 10-25 years compared to the general population. Approximately 30% of patients are resistant to antipsychotic medications, and 60% of these do not respond to clozapine (ultra-refractory). DBS has shown definite efficacy in movement disorders and refractory obsessive-compulsive disorder (OCD) as well as major depressive disorder (MDD). Preliminary studies have indicated that DBS targeting sites such as the NAcc can improve symptoms in some schizophrenia patients. Additionally, abnormal white matter in the anterior limb of the internal capsule has been identified in refractory patients, providing a basis for exploring combined target stimulation.

This study aims to investigate the efficacy and safety of deep brain stimulation of the Nucleus Accumbens and Anterior Limb of the Internal Capsule in the treatment of refractory schizophrenia. A randomized controlled (self-controlled) design is adopted. The statistical analysis unit generates a random allocation table using SAS software, and groups are assigned via central randomization. Both groups undergo three stimulation phases: DBS activation 2 weeks after surgery, 6 weeks of single-target stimulation followed by 2 weeks of shutdown, another 6 weeks of alternate single-target stimulation followed by 2 weeks of shutdown, and finally 6 weeks of combined dual-target stimulation. Trial Group 1 is stimulated sequentially at NAcc, Anterior Limb of the Internal Capsule, and dual targets; Trial Group 2 follows the reverse order for single-target stimulation before combined stimulation. Surgery is performed under general anesthesia by neurosurgeons with associate senior titles or above and extensive experience. After head frame placement, CT and MRI images are fused for targeting. Electrodes are implanted into the NAcc via the Anterior Limb of the Internal Capsule, and a pulse generator is placed under the clavicle and connected to the electrodes. Postoperative CT confirms electrode position. Trial devices are provided by Jingyu Medical Technology (Suzhou) Co., Ltd., including implantable neurostimulation systems, electrode leads, extension leads, and programming equipment. On-site follow-up is conducted at key time points: screening, baseline, 2 weeks postoperatively (DBS activation), 6 weeks after stimulation, 16 weeks postoperatively, and 24 weeks postoperatively, including scale assessments, physical examinations, and laboratory/imaging tests. The primary outcome measure was the reduction rate of the total PANSS score at 24 weeks after DBS implantation compared to baseline, with a 20% reduction defined as effective, assessed by independent psychiatric evaluators.

Conditions

• Refractory Schizophrenia

Interventions

DEVICE

Deep Brain Stimulation

An assessment is conducted 7 days postoperatively. DBS is activated 2 weeks after implantation for NAcc-only stimulation. Stimulation is maintained for 6 weeks (until week 8 postoperatively), then shut down. Stimulation is reactivated at week 10 for anterior limb of the internal capsule-only stimulation, maintained for 6 weeks (until week 16 postoperatively), then shut down. Based on the participant's vital signs and motor responses to stimulation, initial parameters are set as: 2.5-7.5 V, pulse width 60-210 µs, frequency 80-210 Hz. During the stabilization phase, an independent clinical programmer adjusts parameters individually for each patient based on clinical status and provides guidance according to symptom changes. Patients are not informed of any adjustments. To maximize therapeutic efficacy, the adjustment sequence is: (1) increase voltage up to 7.5 V; (2) increase pulse width or frequency up to 210 µs/Hz; (3) change contacts or modes (monopolar negative or bipolar negative).

DEVICE

Deep Brain Stimulation

An assessment is conducted 7 days postoperatively. DBS is activated 2 weeks after implantation for anterior limb of the internal capsule-only stimulation. Stimulation is maintained for 6 weeks (until week 8 postoperatively), then shut down. Stimulation is reactivated at week 10 for NAcc-only stimulation, maintained for 6 weeks (until week 16 postoperatively), then shut down.Based on the participant's vital signs and motor responses to stimulation, initial parameters are set as: 2.5-7.5 V, pulse width 60-210 µs, frequency 80-210 Hz. During the stabilization phase, an independent clinical programmer adjusts parameters individually for each patient based on clinical status and provides guidance according to symptom changes. Patients are not informed of any adjustments. To maximize therapeutic efficacy, the adjustment sequence is: (1) increase voltage up to 7.5 V; (2) increase pulse width or frequency up to 210 µs/Hz; (3) change contacts or modes (monopolar negative or bipolar negative).

Sponsors & Collaborators

• First Affiliated Hospital of Fujian Medical University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-01-20

Primary Completion

2026-12-31

Completion

2026-12-31