Efficacy and Biomarkers of Response of TBS in Treatment Resistant Depression

Not Applicable

Recruiting

• Conditions: Resistant Depression, Treatment; Bipolar Depression
• Interventions: Device: Theta Burst Transcranial Magnetic Sham Stimulation; Device: Theta Burst Transcranial Magnetic Bilateral Stimulation; Device: Theta Burst Transcranial Magnetic Unilateral Stimulation

• Registration Number: NCT04998773
• Lead Sponsor: Instituto de Investigacion Sanitaria La Fe

Brief Summary

Theta Burst Transcranial Magnetic Stimulation (TBS) in dorsolateral prefrontal cortex (DLPFC) has shown efficacy and safety as an adjuvant strategy for resistant to treatment depression (RTD) in daily sessions during 4-6 weeks (20-30 sessions). Current investigation in TBS aims to design intensive treatment protocols so as to achieve earlier responses and higher rates of efficacy. However, the implementation of TBS in the Public National Health Service requires cost-effective protocols that ensure and facilitate patients adherence to treatment, and whose design is based on clinical and neuroimaging biomarkers of response so as to adequately select candidate patients. The aim of this study is to assess the efficacy and safety of novel bilateral and unilateral intensive and spaced protocols of TBS in outpatients with unipolar and bipolar RTD compared with sham stimulation. Specific objectives: I) Comparison of mood change, response and remission of depressive illness at the end of TBS protocol in the groups and maintenance of its effect at 3 months; II) Characterization of neuroimaging cerebral connectivity networks and cerebral metabolism patterns of patients with RTD related to the effects of bilateral or unilateral TBS; III) Identification of clinical and demographic predictors contributing to response to TBS; IV) Analysis of the interaction between clinical, demographic and neuroimaging predictors so as to determine a RTD profile of patient that can benefit from TBS.

Detailed Description

Participants will receive 22 bilateral sessions of sham/active continuous (right DLPFC) and intermittent (left DLPFC) TBS during 6 weeks. Simultaneous cerebral PET-MRI will be performed before (week 0) and after the treatment with TBS (week 7)

* Weeks 1 and 2: 1 session 5 days a week (10 sessions)

* Weeks 3,4,5, 6: 1 session 3 days a week (12 sessions)

Study Timeline

• Study First Submitted: 2021-08-02
• Study First Submitted QC: 2021-08-02
• Study First Posted: 2021-08-10
• Study Start: 2021-09-15
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-21
• Last Update Posted: 2024-02-22
• Primary Completion: 2025-02
• Study Completion: 2025-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 96

Inclusion Criteria

• Diagnosis of Major Depressive Episode or Depressive phase in Bipolar Disorder DSM-5 criteria.
• Moderate severity (>14 points in HDRS)
• 2 antidepressant failures or failure in enhancing strategies in the case of bipolar depression.
• No changes in treatment 3 week previous to the onset of treatment with TMS.
• Ability to sign informed consent.

Exclusion Criteria

• Any psychiatric comorbidity in axis I or II.
• Depressive episode with psychotic features.
• Dysthymia.
• Treatment with ECT in current depressive episode.
• Multiresistance (> 6 trials of therapeutic strategies).
• Suicide risk assessed previous to each session.
• Patients who miss 2 TMS sessions in a row
• Neurological comorbidities (epilepsy, Parkinson disease, neurocognitive disorders).
• Contraindications to TMS: pregnancy, metallic cervical or head implants.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group Placebo	Theta Burst Transcranial Magnetic Sham Stimulation	32 patients, bilateral sham TBS stimulation. Will receive an intensive-spaced protocol of Sham Intermittent TBS in left DLPFC and Sham Continuous TBS in right DLPFC
Group Bilateral	Theta Burst Transcranial Magnetic Bilateral Stimulation	32 patients, bilateral active TBS stimulation, Will receive an intensive-spaced protocol Intermittent TBS in left DLPFC and Continuous TBS in right DLPFC
Group Unilateral	Theta Burst Transcranial Magnetic Unilateral Stimulation	32 patients, unilateral left DLPFC active TBS stimulation. Will receive an intensive-spaced protocol Intermittent TBS in left DLPFC and Sham Continuous TBS in right DLPFC

Primary Outcome Measures

Name	Time	Method
Hamilton Depression Rating Scale 17 items (HDRS-17) at the end of the treatment respect to basal.	6 weeks	Hetero-administered

Secondary Outcome Measures

Name	Time	Method
Beck Depression Inventory (BDI-II) respect to basal.	2, 6 weeks	Self-administered
Montgomery Asberg Depression Rating Scale (MADRS) respect to basal.	2, 6 weeks	Hetero-administered
Screening for Cognitive Impairment por Psychiatry (SCIP) at the end of the treatment respect to basal.	6 weeks	Hetero-administered (versions A and B)
Dimensional Apathy Scale (DAS) respect to basal	6 weeks	Self-administered
Altman Self Rating Mania Scale (ASRM) at the end of the treatment respect to basal.	2, 6 weeks	Self-administered
Young Mania Rating Scale (YMRS) at the end of the treatment respect to basal.	2, 6 weeks	Hetero-administered
Short Form Health Survey (SF 36) at the end of the treatment respect to basal.	6 weeks	Self-administered
Remission	2 and 6 weeks	MADRS\<11 POINTS
Clinical Global Impression Scale (CGI) respect to basal.	2,6 weeks	Hetero-administered
Hamilton Anxiety Scale (HAM-A) respect to basal.	2,6 weeks	Hetero-administered
Response to treatment	2 and 6 weeks	50% reduction in MADRS
Oviedo Sleep Questionnaire (OSQ) respect to basal.	2, 6 weeks	Hetero-administered
Functional Assessment Short Test (FAST) at the end of the treatment respect to basal.	6 weeks	Hetero-administered
Global assessment of Functioning (GAF) at the end of the treatment respect to basal.	6 weeks	Hetero-administered

Trial Locations

Locations (1)

Hospital Universitario y Politécnico La Fe; 🇪🇸 Valencia, Spain