Efficacy and Biomarkers of Response of TBS in Treatment Resistant Depression (EMTtfNI)

Instituto de Investigacion Sanitaria La Fe

Status: Enrolling

Conditions: Bipolar Depression; Resistant Depression, Treatment

Treatments: Device: Theta Burst Transcranial Magnetic Unilateral Stimulation; Device: Theta Burst Transcranial Magnetic Bilateral Stimulation; Device: Theta Burst Transcranial Magnetic Sham Stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT04998773

21-0040 (Other Identifier)

2021-326-1

PI 2022-280-1 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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)

Enrollment: 96 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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96 participants in 3 patient groups, including a placebo group

Group Bilateral

Active Comparator group

Description:

32 patients, bilateral active TBS stimulation, Will receive an intensive-spaced protocol Intermittent TBS in left DLPFC and Continuous TBS in right DLPFC

Treatment:

Device: Theta Burst Transcranial Magnetic Bilateral Stimulation

Group Unilateral

Active Comparator group

Description:

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

Treatment:

Device: Theta Burst Transcranial Magnetic Unilateral Stimulation

Group Placebo

Placebo Comparator group

Description:

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

Treatment:

Device: Theta Burst Transcranial Magnetic Sham Stimulation