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

NCT ID: NCT04530942

Last Updated: 2024-03-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-29
• Study Completion Date: 2024-12-30

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.

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.

Conditions

Major Depressive Disorder; Deep Brain Stimulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Deep brain stimulation(Active)

Intervention Type: DEVICE

DBS On with the optiomal parameters

Deep brain stimulation(Sham)

Intervention Type: DEVICE

DBS On with 0V Amplitude

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.

Group Type: EXPERIMENTAL

Deep brain stimulation(Active)

Intervention Type: DEVICE

DBS On with the optiomal parameters

Deep brain stimulation(Sham)

Intervention Type: DEVICE

DBS On with 0V Amplitude

Interventions

Deep brain stimulation(Active)

DBS On with the optiomal parameters

Intervention Type: DEVICE

Deep brain stimulation(Sham)

DBS On with 0V Amplitude

Intervention Type: DEVICE

Other Intervention Names

DBS On; DBS Off

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Bomin Sun

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bomin Sun, PhD

Role: PRINCIPAL_INVESTIGATOR

Ruijin Hospital

Locations

Functional neurosurgery of Shanghai Jiaotong University affiliated Ruijin Hospital

Shanghai, , China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 25726497 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27049915 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29483673 (View on PubMed)

Other Identifiers

2020 DBS for TRD

Identifier Type: -

Identifier Source: org_study_id