iTBS-TMS for Bipolar Disorder

Recruiting at 1 trial location

Overseen By Kristen K Ellard, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must be taking: Mood stabilizers

Must not be taking: Benzodiazepines

Disqualifiers: Mania, Psychosis, Substance use, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 1 week

136 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants have a stable medication regimen for at least one month, including a mood stabilizer. However, you cannot be on benzodiazepines, as they can interfere with the treatment.

What data supports the effectiveness of the treatment Intermittent Theta Burst Stimulation (iTBS) for Bipolar Disorder?

Research shows that iTBS can lead to high response and remission rates in patients with bipolar depression, with 72% of patients responding and 42% achieving remission in one study. This suggests that iTBS may be an effective treatment option for bipolar depression, although larger studies are needed to confirm these findings. ^{1 2 3 4 5}

Is iTBS-TMS safe for humans?

Research shows that iTBS, a form of transcranial magnetic stimulation, is generally safe for humans, with studies reporting no adverse events in patients with bipolar depression and treatment-resistant depression. ^{4 5 6 7 8}

How is iTBS-TMS treatment different from other treatments for bipolar disorder?

iTBS-TMS is a unique treatment for bipolar disorder because it uses magnetic pulses to stimulate specific brain areas in a very short time, potentially improving mood and cognitive functions without the need for medication. Unlike traditional treatments, it can be administered quickly and has shown promising results in improving depression symptoms with minimal side effects. ^{1 4 5 6 7}

What is the purpose of this trial?

The objective of this study protocol is to test whether intermittent theta-burst transcranial magnetic stimulation (iTBS-TMS) to the inferior parietal lobule (IPL) can strengthen functional connectivity with a key region in emotion regulation (ER) neurocircuitry (anterior insula, AI) and improve performance on ER-related tasks in patients with bipolar disorder. Individual IPL sites for stimulation will be identified through baseline, pre-TMS functional magnetic resonance imaging (fMRI) scans. Patient-specific IPL subregions showing positive functional connectivity with the anterior insula and falling within the patient-specific frontoparietal control network will be used as individualized target sites for TMS stimulation. Patients will be randomized to receive 24 sessions of active versus sham iTBS to patient-specific IPL targets (6 sessions/day, 4 days, 43,200 pulses total). Post-iTBS resting-state and task-based fMRI scans will be acquired 3 days after the final day of iTBS administration (Day 4) following identical procedures as baseline. Effects of iTBS-TMS on ER will be evaluated by comparing pre-TMS versus post-TMS functional connectivity and behavior during performance on ER tasks.

Research Team

Kristen K Ellard, PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for individuals with bipolar disorder. Participants will be selected based on their brain imaging scans and must have a specific connection in the brain that can be targeted by the treatment. They should be able to complete multiple sessions over several days.

Inclusion Criteria

I am between 24 and 65 years old.

Ability to provide informed consent and verifiable contact information, including current psychiatric treatment provider

Diagnostic Statistical Manual (DSM-5) defined diagnosis of bipolar I or II disorder (BD) assessed using the Mini-International Neuropsychiatric Interview (M.I.N.I.) version 7.0.2

Exclusion Criteria

History of psychosis

I don't have metal implants, a history of seizures, or serious head injuries.

Current mania/hypomania assessed by the Young Mania Rating Scale (YMRS > 12)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 24 sessions of active or sham intermittent theta burst stimulation (iTBS) over 4 days

1 week

6 sessions/day for 4 days

Follow-up

Participants are monitored for changes in functional connectivity and behavior through fMRI and computer-based tasks

4 weeks

1 visit (in-person) for fMRI and tasks

Treatment Details

Interventions

• Intermittent Theta Burst Stimulation (iTBS)

Trial Overview The study tests if iTBS-TMS, a non-invasive brain stimulation technique, can improve emotion regulation in bipolar patients by targeting a specific brain area identified through fMRI scans. Patients receive either real or sham TMS over four days to see if it affects their emotional control.

Participant Groups

Group I: Active intermittent theta burst stimulation (iTBS) Experimental Treatment 1 Intervention

The Active intermittent theta burst stimulation (iTBS) arm will receive active iTBS applied to the inferior parietal lobule (IPL)

Group II: Sham intermittent theta burst stimulation (iTBS) Placebo Group 1 Intervention

The Sham intermittent theta burst stimulation (iTBS) arm will receive sham iTBS applied to the inferior parietal lobule (IPL)

Intermittent Theta Burst Stimulation (iTBS) is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Migraines
• Smoking Cessation

Approved in European Union as rTMS for:

• Major Depressive Disorder (MDD)

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Findings from Research

A clinical trial involving 37 participants with acute bipolar depression found that intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex was not effective, as there were no significant differences in depression scores between the active and sham treatment groups.

The study was terminated for futility, indicating that iTBS did not show clinical benefits in reducing depression symptoms, and only a small percentage of participants responded to treatment, highlighting the need for further research on TMS protocols in bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Active vs Sham Intermittent Theta Burst Transcranial Magnetic Stimulation for Patients With Bipolar Depression: A Randomized Clinical Trial. McGirr, A., Vila-Rodriguez, F., Cole, J., et al.[2021]

In a study involving 19 patients with acute-phase bipolar depression, continuous theta burst stimulation (cTBS) was found to be safe and well-tolerated, with no major adverse effects reported.

Despite the treatment being safe, the efficacy of cTBS in significantly improving depression symptoms was inconclusive, as no statistically significant differences were observed between the active and sham treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Continuous Theta Burst "Intensive" Stimulation in Acute-Phase Bipolar Depression: A Pilot, Exploratory Study. Mallik, G., Mishra, P., Garg, S., et al.[2023]

In a study of 60 patients with treatment-resistant unipolar depression, both intermittent theta burst stimulation (iTBS) and conventional 10 Hz rTMS showed similar efficacy in reducing depression scores and improving quality of life over a 6-month follow-up, with response rates of 36.7% for iTBS and 33.3% for rTMS.

iTBS is highlighted as a more time-efficient and cost-effective option compared to rTMS, suggesting it could be a valuable treatment alternative for patients with severe depression who have not responded to multiple antidepressant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). Bulteau, S., Laurin, A., Pere, M., et al.[2022]

In a study involving 31 patients with bipolar depression, intermittent theta burst stimulation (iTBS) did not show significant cognitive improvements compared to sham stimulation over four weeks.

However, there was a trend indicating increased left hippocampal volume in the active group, which correlated with improvements in nonverbal memory, suggesting potential neuroplastic changes that could support cognitive enhancement in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of intermittent theta-burst transcranial magnetic stimulation on cognition and hippocampal volumes in bipolar depression. Torres, IJ., Ge, R., McGirr, A., et al.[2023]

In a study of 26 patients with bipolar depression, active intermittent theta burst stimulation (iTBS) showed a high response rate of 72% and a remission rate of 42%, indicating its potential efficacy in treating this condition.

No adverse events were reported, demonstrating that iTBS is safe and well-tolerated, but further research with larger sample sizes is needed to confirm its superiority over sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. Bulteau, S., Beynel, L., Marendaz, C., et al.[2020]

Intermittent theta-burst stimulation (iTBS) and high-frequency rTMS (HF-rTMS) show similar efficacy in treating treatment-resistant depression (TRD), with response rates of 48.0% for iTBS and 45.5% for HF-rTMS based on two high-quality randomized controlled trials involving 474 participants.

Both iTBS and HF-rTMS have comparable safety profiles, with similar rates of discontinuation and adverse events, such as headaches, indicating that iTBS is a safe alternative to HF-rTMS for patients with TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. Lan, XJ., Yang, XH., Qin, ZJ., et al.[2023]

In a study involving 208 participants with treatment-resistant depression, both twice-daily and once-daily intermittent theta burst stimulation (iTBS) protocols showed improvements in depression scores, but there was no significant difference in efficacy between the two schedules after 10 and 30 days.

Response and remission rates were low in both treatment groups, indicating that neither protocol significantly accelerated the improvement of depressive symptoms in patients with treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study. Blumberger, DM., Vila-Rodriguez, F., Wang, W., et al.[2022]

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Active vs Sham Intermittent Theta Burst Transcranial Magnetic Stimulation for Patients With Bipolar Depression: A Randomized Clinical Trial. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Continuous Theta Burst "Intensive" Stimulation in Acute-Phase Bipolar Depression: A Pilot, Exploratory Study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). [2022]

4. England pubmed.ncbi.nlm.nih.gov

Effects of intermittent theta-burst transcranial magnetic stimulation on cognition and hippocampal volumes in bipolar depression. [2023]

5. France pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. [2022]