The Efficacy and Prediction of Deep Brain Stimulation for Treatment-resistant Depression

NCT04530942 | Active Not Recruiting

• 1 other identifier: 2020 DBS for TRD
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Several open-label trials have shown the therapeutic promise of deep brain stimulation (DBS) targeted to striatal and surrounding capsular areas in treatment-resistant depression (TRD). However, the results of placebo-controlled trials have been mixed, with one showing a large difference between active and sham DBS and another finding no difference. Main aim of this study is establishing whether active DBS results in more treatment responders than sham DBS. Secondary aims are establishing an adverse events profile, establishing effects on quality of life,neuropsychological and neuroimaging measures, and finding predictors of response.

Conditions

Major Depressive Disorder; Deep Brain Stimulation

Keywords

Treatment Resistant Depression; Deep Brain Stimulation; Ventral Capsule/Ventral Striatum

Outcome Measures

Primary Outcomes (1)

• the comparison between the Hamilton Depression Scale(HAMD-17) scores after active and sham phase

  Effect size of comparison between HAMD-17 scores at two weeks when the active and sham phase end. The score of HAMD-17 ranges from 0 to 50. Higher HAMD-17 score indicates more severe depression.

  Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months

Secondary Outcomes (9)

• changes in the Montgomery-Asberg Depression Rating Scale(MADRS)

  Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months

• changes in the Quick Inventory of Depression Scale(QIDS-SR16)

  Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months

• changes in the Depression and Somatic Symptoms Scale(DSSS)

  Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months

• changes in the Dimensional Anhedonia Rating Scale(DARS)

  Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months

• changes in Hamilton Anxiety Scales(HAMA)

  Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months

Study Arms (2)

Active DBS then Sham DBS

EXPERIMENTAL

After more than 6 months open-lable period, some patients will take DBS ON for two weeks with the optimal stimulation parameters and then take DBS OFF for two weeks.

Device: Deep brain stimulation(Active); Device: Deep brain stimulation(Sham)

Sham DBS then Active DBS

EXPERIMENTAL

After more than 6 months open-lable period, some patients will take DBS OFF for two weeks and then take DBS ON for two weeks with the optimal stimulation parameters.

Device: Deep brain stimulation(Active); Device: Deep brain stimulation(Sham)

Interventions

Deep brain stimulation(Active) DEVICE

DBS On with the optiomal parameters

Also known as: DBS On

Active DBS then Sham DBS; Sham DBS then Active DBS

Deep brain stimulation(Sham) DEVICE

DBS On with 0V Amplitude

Also known as: DBS Off

Active DBS then Sham DBS; Sham DBS then Active DBS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary diagnosis: Major Depressive Disorder according to the ICD-10 criteria based on a psychiatric interview
• Age: 18-65 years old
• HAMD-17 total ≥17
• Chronic illness with current episode ≥ 24 months duration and/or Illness with at least a total of 4 lifetime episodes (including current episode≥ 12 months) and a minimum of 5 years since the onset of the first depressive episode
• Treatment refractory defined as failure of: at least 3 adequate treatments from at least two distinctly different classes (SSRI, SNRI, NaSSA, TCA +, lithium-addition) for a period of 6-8 weeks or more weeks. Adequate psychotherapy. At least 1 session of ECT, for which the series of ECT was terminated either due to adverse effects or insufficient response (including at least 6 sessions of bilateral ECT); unavailable, rejective or intolerable to ECT
• remain stable with the current anti-depressive medicine for the last month
• Able and willing to give written informed consent
• Able to fully understand the consequences of the procedure

You may not qualify if:

• Schizophrenia /history of psychosis unrelated to MDD
• Severe personality disorder (assessed by SCID-II)
• Abnormal brain MRI
• Neurological disease (e.g., Parkinson's disease)
• Previous sterosurgery
• Any medical contraindication to surgery

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Functional neurosurgery of Shanghai Jiaotong University affiliated Ruijin Hospital

Shanghai, China

Location

Related Publications (4)

• Dougherty DD, Rezai AR, Carpenter LL, Howland RH, Bhati MT, O'Reardon JP, Eskandar EN, Baltuch GH, Machado AD, Kondziolka D, Cusin C, Evans KC, Price LH, Jacobs K, Pandya M, Denko T, Tyrka AR, Brelje T, Deckersbach T, Kubu C, Malone DA Jr. A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression. Biol Psychiatry. 2015 Aug 15;78(4):240-8. doi: 10.1016/j.biopsych.2014.11.023. Epub 2014 Dec 13.

  PMID: 25726497 BACKGROUND

• Bergfeld IO, Mantione M, Hoogendoorn ML, Ruhe HG, Notten P, van Laarhoven J, Visser I, Figee M, de Kwaasteniet BP, Horst F, Schene AH, van den Munckhof P, Beute G, Schuurman R, Denys D. Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2016 May 1;73(5):456-64. doi: 10.1001/jamapsychiatry.2016.0152.

  PMID: 27049915 BACKGROUND

• Dandekar MP, Fenoy AJ, Carvalho AF, Soares JC, Quevedo J. Deep brain stimulation for treatment-resistant depression: an integrative review of preclinical and clinical findings and translational implications. Mol Psychiatry. 2018 May;23(5):1094-1112. doi: 10.1038/mp.2018.2. Epub 2018 Feb 27.

  PMID: 29483673 BACKGROUND

• Wang L, Zhang Y, Wang Y, Ding Q, Dai L, Hu K, Ye K, Lv X, Zhang X, Mandali A, Manssuer L, Sonkusare S, Zhao Y, Huang P, Qiu X, Pan Y, Lai Y, Li D, Liu W, Zhan S, Sun B, Voon V. Prefrontal-bed nucleus of the stria terminalis physiological and neuropsychological biomarkers predict therapeutic outcomes in depression. Nat Commun. 2025 Nov 18;16(1):10034. doi: 10.1038/s41467-025-65179-z.

  PMID: 41253805 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Bomin Sun, PhD

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The study starts with a longitudinal open-label phase followed by a randomized, double blind crossover phase. In the crossover phase, patients are randomized to active DBS for 2 weeks, followed by sham DBS for 2 weeks, or vice versa. The patients' post-surgery duration need to be more than 6 months when they entered the randomized cross-over phase.

Study Record Dates

• First Submitted: August 25, 2020
• First Posted: August 28, 2020
• Study Start: March 29, 2021
• Primary Completion: April 30, 2024
• Study Completion: December 30, 2024
• Last Updated: March 25, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)