Repetitive Transcranial Magnetic Stimulation for Treating Resistant Bipolar Depression

Study Overview
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Brief Summary
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The aim of this randomized, single-blind trial is to evaluate the effectiveness and tolerability of high frequency or low frequency repetitive transcranial magnetic stimulation (rTMS) in patients with resistant bipolar depression. Patients will be assigned to receive either high or low frequency rTMS for 20 consecutive workdays (4 weeks). 10 Hz (high) frequency rTMS and 1 Hz (low) frequency rTMS will be given over the left or right dorsolateral prefrontal cortex (DLPFC), respectively. Patients will be assessed with several psychometric instruments at baseline, and at weeks 5 and 9.

Official Title
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A Randomized Trial Comparing the Effectiveness and Tolerability of High and Low Frequency Repetitive Transcranial Magnetic Stimulation for Treating Resistant Bipolar Depression: An Exploratory Study

Conditions
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Bipolar Depression

Intervention / Treatment
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* Device: Magstim Rapid2 Stimulator
* Device: Magstim Rapid2 Stimulator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women aged 18 to 70 years Current major depressive episode (MDE) in the context of a bipolar disorder type I or II (according to the DSM-IV-TR) that has not improved after more than 2 adequate pharmacological trial(s) in the current episode (failure is defined as a lack of significant clinical improvement after the use of standard mood stabilizers, atypical antipsychotics and/or antidepressants given at their minimum effective dosage or higher for at least 4 weeks of duration) Baseline score ≥ 13 on the Quick Inventory of Depressive Symptomatology - Clinician-Administered (QIDS-C), i.e., a MDE of at least moderate intensity Exclusion Criteria: Psychotic features in the current episode Lifetime history of a non-mood-related psychotic disorder Substance or alcohol abuse/dependence in the past 6 months Unstable medical disease (e.g., cardiovascular, renal) Presence of mood cycles of < 30 days duration Pregnancy and/or lactation Presence of a specific contraindication for rTMS (e.g., personal history of epilepsy or convulsion, metallic head implant) Hearing loss

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Frequency rTMS<br>10 Hz in 75 trains of 4-seconds duration, with 26-seconds intertrain intervals (3,000 pulses per session) at 120% of the rMT. | Device: Magstim Rapid2 Stimulator<br>* 10 Hz in 75 trains of 4-seconds duration, with 26-seconds intertrain intervals (3,000 pulses per session) at 120% of the rMT.<br>* Other names: 10 Hz rTMS;|
| Experimental: Low Frequency rTMS<br>1 Hz in 1 train of 20-minute duration (1,200 pulses per session) at 120% of the rMT. | Device: Magstim Rapid2 Stimulator<br>* 1 Hz in 1 train of 20-minute duration (1,200 pulses per session) at 120% of the rMT.<br>* Other names: 1 Hz rTMS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) | Pre-post neuromodulation treatment reduction on the scores of the MADRS | Week 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 21-item Hamilton Depression Rating Scale (HAM-D21) | Response to treatment will be defined as a higher than 50% reduction in pretreatment symptoms severity as measured by the mean HAM-D21 score. Remission will be considered as a HAM-D21 score ≤ 8. | Week 5 | 
| Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) | Response to treatment will be defined as a higher than 50% reduction in pretreatment symptoms severity as measured by the mean QIDS-SR score. Remission will be considered as a QIDS-SR score ≤ 5. | Week 5 | 
| Quick Inventory of Depressive Symptomatology - Clinician (QIDS-C) | Response to treatment will be defined as a higher than 50% reduction in pretreatment symptoms severity as measured by the mean QIDS-C score. Remission will be considered as a QIDS-C score ≤ 5. | Week 5 | 
| Montogmery-Asberg Depression Rating Scale (MADRS) | Response to treatment will be defined as a higher than 50% reduction in pretreatment symptoms severity as measured by the mean MADRS score. Remission will be defined as a MADRS score ≤ 6. | Week 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Repetitive transcranial magnetic stimulation, Bipolar depression, Randomized trial, rTMS, Neuromodulation