Efficacy of rTMS in Bipolar Depression

Not Applicable

Terminated

Conditions: Bipolar Depression

Interventions: Device: Sham rTMS
Device: iTBS repetitive Transcranial Magnetic Stimulation (rTMS)

Registration Number: NCT02749006

Lead Sponsor: University of British Columbia

Brief Summary: Bipolar Disorder is a common condition that is characterized by periods of mood elevation however periods of chronic and recurring depressive episodes are more common and can be severely disabling. Effective treatments exist, however a significant portion of bipolar depressed patients do not respond to, or have difficulty tolerating many of these interventions. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulatory technique that is effective in major depression and there is evidence for its efficacy in bipolar depression which needs to be assessed in larger randomized controlled trials. This study is a randomised, double-blind, sham-controlled trial over four weeks. The primary objective is to assess improvement in depressive symptoms in acute bipolar depressed patients on treatment with intermittent Theta-Burst Stimulation (iTBS) in comparison to sham-rTMS.

Detailed Description: rTMS is a treatment that involves stimulating a certain area of the brain with magnetic field pulses. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region and help symptoms of bipolar depression. The device used in this study has been approved by Health Canada for therapeutic use since 2002. Participants will complete a screen visit to determine eligibility based on the inclusion/exclusion criteria. If the participants are not eligible, no further study procedures will be conducted. Eligible subjects will be randomized to receive either active iTBS-rTMS or sham rTMS treatment (scalp stimulation with no magnetic pulse) daily for four weeks (20 sessions) to the left dorsolateral prefrontal cortex (DLPFC). All participants will complete a MRI (to target the left DLPFC region of the brain and functional activity), EEG \& fNIRS, lab work, and neurocognitive testing prior to the commencement and post rTMS treatment. Efficacy, safety and tolerability will be evaluated at screen visit, during daily rTMS treatments, clinic visits and post rTMS treatment. All participants will have a phone interview two weeks post rTMS treatment.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 37

Inclusion Criteria

Are a male or female aged 18 to 70 years.
Have a diagnosis of Bipolar Disorder with a current ongoing episode of depression.
Are not currently experiencing a mania.
Have failed to achieve a clinical response or have been unable to tolerate an adequate dose of at least one of the medications used for treating Bipolar depression
Are taking an anti-manic agent (lithium or valproate) or an atypical antipsychotic (quetiapine, lurasidone, aripiprazole, ziprasidone, risperidone, olanzapine), or a combination of the above, or a combination of any of them with lamotrigine 100-400 mg daily. Lamotrigine alone for bipolar II disorder is permitted.
current medications have been at a stable dose in the 2 weeks prior to randomization
Are capable of understanding, consenting to, and complying with the requirements of the study

Exclusion criteria:

Have an alcohol or substance abuse or dependence within the last 3 months.
Are at a significant risk of harm to themselves or others
Are pregnant or planning on becoming pregnant in near future or lactating.
Have a personal or family history of seizures.
Have a history of unstable or inadequately treated medical illnesses, including moderate to severe brain injury or head trauma.
Have a primary diagnosis of other psychiatric disorders (other than Bipolar) or personality disorders that are of primary concern and causing greater impairment other than bipolar disorder.
are currently taking more than 3 of the antipsychotics.
Have failed a course of ECT in the current episode.
History of non-response to rTMS treatment.
If participating in psychotherapy, you must have been in stable treatment for at least 3 months prior to entry into the study,
Currently (or in the last 4 weeks) taking more than 2 mg daily (or equivalent) of lorazepam or any dose of medication for seizures
Have a pacemaker, or an implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth that cannot be safely removed.
Have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham rTMS	Sham rTMS	sham rTMS treatment involves scalp stimulation with no magnetic pulse daily for four weeks (20 sessions). Sham rTMS involves only the click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.
Active iTBS rTMS	iTBS repetitive Transcranial Magnetic Stimulation (rTMS)	The active arm involves magnetic stimulation of the brain to the left dorsolateral prefrontal cortex (DLPFC) daily for four weeks. The active arm will be receiving intermittent Theta-Burst (iTBS) repetitive Transcranial Magnetic Stimulation (rTMS) to deliver magnetic pulses.

Primary Outcome Measures

Name	Time	Method
Montgomery Asberg Depression Rating Scale (MADRS) Scale Score	Baseline, Week 2, Week 4	The primary outcome was the change in score on the Montgomery-Asberg Depression Rating Scale from baseline to study end. A higher score means a worse outcome. Min value is 0, Max value is 60

Secondary Outcome Measures

Name	Time	Method
Number of Participants Meeting Criteria for Clinical Remission	Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)	Clinical Remission is defined as a MADRS score ≤12
Sheehan Disability Scale (SDS)	Baseline to 4 weeks	The Sheehan Disability Scale is a five-item, self-rated questionnaire designed to measure the extent to which a patient's disability due to an illness interferes with work/school, social life/leisure activities, and family life/home responsibilities. Each subscale score (a work disability, a social life disability, a family life disability) is combined into a single total score (sum of the non missing responses for items 1-3) representing a global impairment rating, ranging from 0 to 30, with higher scores indicative of significant functional impairment.
Quality of Life Questionnaire	Baseline to 4 weeks	The Quality of Life in Bipolar Disorder scale is a 56 item scale which assesses 12 core and 2 optional (work and study) domains, each containing four self-report items (1: strongly disagree to 5: strongly agree). An overall score (range: 48-240) may be calculated by summing responses to the 48 items of the core 12 domains. Higher scores reflect greater satisfaction with a person's quality of life.
Patient Global Impression Rating Scale- Improvement	Week 4	Rates current depression compared to baseline. Min =1 Max =7 Higher scores mean worse outcome.
Number of Participants With Clinical Response	Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)	Response rates are defined as patients showing ≥50% reduction in MADRS scores.
Patient Global Impression Rating Scale: Severity	Baseline to 4 weeks	Patient Global Impression Rating Scale: Severity rates how depressed the participant is at the current time. 1-4 (1 is normal and 4 is severe)
Overall Well Being	Baseline to 4 weeks	The visual analog scale (VAS) is a self report measure that captures the over all well being. Min 0-worse health to Max 100- best health.
Brief Illness Perception Questionnaire	Baseline to 4 weeks	Brief Illness Perception Questionnaire measures participant's perception of illness. Min = 0 Max = 80. Higher score means worse outcome.