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

March 21, 2024 updated by: Bomin Sun, Ruijin Hospital

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder, with an estimated lifetime prevalence of 14.6% across high-income countries.Effective therapeutic options for MDD include psychotherapy, different classes of antidepressants, and electroconvulsive therapy (ECT). Nevertheless, up to 30% of patients do not respond to four consecutive antidepressant strategies and 52% of pharmacotherapy resistant patients do not respond to ECT.Such patients are designated an advanced stage of Treatment Resistant Depression (TRD), which is associated with more hospitalizations, more suicide attempts, and higher costs than non-TRD patients.

Deep Brain Stimulation (DBS) is a promising therapeutic option for TRD patients. DBS consists of implanting electrodes in specific brain areas and then optimizing stimulation parameters (e.g. voltage, frequency, pulse width) to modulate brain activity of the targeted area. Since 2005, several open label trials have reported promising effects of DBS in TRD, targeting different brain structures involved in the neurobiology of MDD: the Subcallosal Cingulate Gyrus (SCG),Medial Forebrain Bundle (MFB),Ventral Capsule/Ventral Striatum (VC/VS), and Nucleus Accumbens (NAc). Response rates, defined as a symptom decrease of at least 50%, range from 30% to 90% with most studies finding a response rate around 50%.

However, results of the first two randomized trials are mixed. The first randomized, controlled trial (RCT) of VC/VS DBS in TRD did not find differences in response rates following active (3 of 14 patients) or sham stimulation (2 of 15 patients) after four months of stimulation. In contrast, another group found a strong antidepressant effect in 16 patients with TRD following active ventral Anterior Limb of the Internal Capsule (vALIC) DBS compared to sham stimulation in a randomized crossover phase.

Therefore, this trial aims to 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.

Study Type

Interventional

Enrollment (Estimated)

34

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Shanghai, China
        • Functional neurosurgery of Shanghai Jiaotong University affiliated Ruijin Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active DBS then Sham DBS
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)
DBS On with the optiomal parameters
Other Names:
  • DBS On
Device: Deep brain stimulation(Sham)
DBS On with 0V Amplitude
Other Names:
  • DBS Off
Experimental: Sham DBS then Active DBS
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)
DBS On with the optiomal parameters
Other Names:
  • DBS On
Device: Deep brain stimulation(Sham)
DBS On with 0V Amplitude
Other Names:
  • DBS Off

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the comparison between the Hamilton Depression Scale(HAMD-17) scores after active and sham phase
Time Frame: Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
changes in the Montgomery-Asberg Depression Rating Scale(MADRS)
Time Frame: Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
Effect size of active compared to sham stimulation score before and after the sham and treatment periods. The score of the scale ranges from 0 to 60. Higher MADRS score indicates more severe depression.
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)
Time Frame: Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
Effect size of active compared to sham stimulation score before and after the sham and treatment periods. The score of the scale ranges from 0 to 42. Higher QIDS-SR16 score indicates more severe depression.
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)
Time Frame: Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
Effect size of active compared to sham stimulation score before and after the sham and treatment periods. The score of the scale ranges from 0 to 66. Higher DSSS score indicates more severe depression and anxiety.
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)
Time Frame: Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
DARS is a self-reported dynamic scale that measures desire, motivation, effort and consummatory pleasure across hedonic domains. Higher scores indicate lower degrees of anhedonia.
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)
Time Frame: Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
Clinician administered assessment.The score of the scale ranges from 0 to 56. The higher scores means more severe anxiety.
Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
changes in World Health Organization Quality of Life-BREF(WHO-BREF)
Time Frame: Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
The World Health Organization Quality of Life - BREF (WHOQOL-BREF) is a self report questionnaire which assesses 4 domains of quality of life (QOL): physical health, psychological health, social relationships, and environment. It contains 26 items which is a 5 points scale. The higher score means better quality of life.
Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
changes in the MOS item short from health survey (SF-36)
Time Frame: Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting and are now widely utilized by managed care organizations and by Medicare for routine monitoring and assessment of care outcomes in adult patients. The higher score means better quality of life.
Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
changes in Sheehan Disability Scale
Time Frame: Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
Self-rating scale. The SDS is a composite of three self-rated items designed to measure the extent to which three major domains in the patient's life are functionally impaired by psychiatric or medical symptoms. The SDS assesses functional impairment in three major life domains: work, social life/leisure activities, and family life/home responsibilities. The higher scores mean more severity of disability.
Baseline (preoperative),one month, 3 months, 6 months, 6.25 months, 6.5 months, 9 months, 12 months, 18months
changes in Neuropsychological measures(Scores of Thinc-it tasks)
Time Frame: Baseline (preoperative), 6.25 months, 6.5 months, 18months
Neuropsychological measures contains six domains of cognition which are episodic memory, working memory,attention, executive functions, psychomotor speed and social cognition.
Baseline (preoperative), 6.25 months, 6.5 months, 18months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ruijin Hospital

Investigators

  • Principal Investigator: Bomin Sun, PhD, Ruijin Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 29, 2021

Primary Completion (Estimated)

April 30, 2024

Study Completion (Estimated)

December 30, 2024

Study Registration Dates

First Submitted

August 25, 2020

First Submitted That Met QC Criteria

August 25, 2020

First Posted (Actual)

August 28, 2020

Study Record Updates

Last Update Posted (Actual)

March 25, 2024

Last Update Submitted That Met QC Criteria

March 21, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020 DBS for TRD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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