Efficacy of rTMS in Bipolar Depression

University of British Columbia37 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Interventions

iTBS repetitive Transcranial Magnetic Stimulation (rTMS)DEVICE

rTMS is a non-invasive procedure in which cerebral electrical activity is influenced by a rapidly changing magnetic field. The magnetic field is created by a plastic-encased coil which is placed over the patient's scalp. The magnetic field can be directed onto specific areas of the brain. rTMS can modulate cerebral activity by low or high frequencies. Over time, the magnetic field pulses can gradually change the activity level of the stimulated brain region and help symptoms of bipolar depression.

Sham rTMSDEVICE

Sham rTMS involves a click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

Montgomery Asberg Depression Rating Scale (MADRS) Scale Score

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

Time frame: Baseline, Week 2, Week 4

Secondary Outcomes

Number of Participants With Clinical Response

Response rates are defined as patients showing ≥50% reduction in MADRS scores.

Time frame: Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)

Number of Participants Meeting Criteria for Clinical Remission

Clinical Remission is defined as a MADRS score ≤12

Time frame: Baseline to Week 4 (assessed at Week 2 and Week 4, Week 4 reported)

Overall Well Being

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.