Effect of Intermittent ThetaBurst Stimulation in Treatment-resistant Bipolar Depression

Study Overview
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Brief Summary
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The aim is to evaluate the evaluate the clinical interest and the safety of repetitive transcranial magnetic stimulation (rTMS) delivered as intermittent Theta burst stimulation(iTBS) on severity of depression in patients with treatment-resistant bipolar disorder.

Detailed Description
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Methods: A double-blind randomized sham-controlled pilot study will be conducted in 40 patients with bipolar treatment-resistant depression receiving either active (n=20) or sham (n=20) iTBS over the left dorsolateral prefrontal cortex. Depression severity will be assessed by an investigator blinded to iTBS condition before and after 10 to 30 iTBS sessions depending on remission onset. Remission will be defined as Beck Depression Inventory, BDI score<10. Objective/Hypothesis: The investigators hypothesized the superiority of active iTBS over sham ITBS

Official Title
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Effects of Intermittent Theta Burst Stimulation Applied Over the Left Dorsolateral Prefrontal Cortex in Patients With Treatment-resistant Bipolar Depression

Conditions
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Bipolar Depression

Intervention / Treatment
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* Device: active iTBS
* Device: sham iTBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders, DSM-IV criteria Montgomery and Asberg depression scale > 20 Exclusion Criteria: other psychiatric features, rapid cycles Benzodiazepines intake pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: active iTBS<br>Participants will receive 10 to 30 sessions of active intermittent theta burst stimulation (iTBS) consisting in delivering 2 s train of bursts containing three pulses at 50 Hz repeated each 200 ms every 10 s (iTBS). Each iTBS session contained 990 pulses and lasted 6 min. Stimulation intensity will be set at 80% of the patient's resting motor threshold. iTBS will be applied twice per day, with at least three hours between each session. Ten to 30 sessions will be delivered until patient achieved remission (i.e., 13-item Beck Depression Inventory (BDI13) score < 10). iTBS will be applied over the left dorsolateral prefrontal cortex (DLPFC) according to the individual's 3D-T1 MRI. | Device: active iTBS<br>* Transcranial magnetic stimulation. MagProX100 (MagVenture, Denmark) with a figure-eight coil (MCF-B65)<br>* Other names: intermittent Theta Burst stimulation; rTMS stimulator, rTMS;|
| Sham Comparator: sham iTBS<br>The same protocol (location, intensity, parameters of stimulation) will be applied using a commercial sham coil. | Device: sham iTBS<br>* Transcranial magnetic stimulation. MagProX100 (MagVenture, Denmark) with a sham figure-eight coil (MCF-P-B65)<br>* Other names: sham intermittent Theta Burst stimulation; sham rTMS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beck Depression Inventory | Self-reported clinical scale with 13 items | 2 time point measure, before and after the end of stimulation sessions (changes from baseline BDI scores at 6 weeks) |