rTMS for Bipolar Disorder

Overseen By Interventional Psychiatry

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Must be taking: Mood stabilizers

Disqualifiers: Substance abuse, Psychotic disorders, Dementia, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether a special type of brain stimulation, called high-dose spaced theta-burst rTMS (repetitive Transcranial Magnetic Stimulation), can reduce symptoms of bipolar depression more effectively than a placebo. Participants will receive either the real rTMS treatment or a sham (fake) version for comparison. The study also seeks biological markers in the brain that could help predict who will benefit from the treatment. Suitable candidates have bipolar depression and have not improved after trying at least two other treatments. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for bipolar depression.

Will I have to stop taking my current medications?

The trial requires that participants be on a stable medication regimen, including at least one mood stabilizer, so you will not have to stop taking your current medications.

What prior data suggests that this rTMS protocol is safe for treating bipolar disorder?

Studies have shown that accelerated theta-burst stimulation (aTBS) is generally safe and well-tolerated. In one study, patients who received aTBS for depression experienced only mild side effects, such as headaches or scalp discomfort. Another research review confirmed that aTBS appears safe, with no serious side effects reported. This treatment targets the left front part of the brain, often associated with mood disorders. Overall, existing evidence suggests that aTBS is a promising and safe option for reducing symptoms of depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for bipolar disorder, which often involve medications like mood stabilizers and antipsychotics, accelerated theta burst stimulation (aTBS) offers a non-invasive brain stimulation approach. This treatment targets the left dorsal lateral prefrontal cortex and is designed to deliver rapid results, potentially showing effectiveness in just five days. Researchers are excited because aTBS could provide quicker relief with fewer side effects compared to existing medication-based therapies, making it a promising option for patients seeking alternative treatments.

What evidence suggests that accelerated theta burst stimulation is effective for bipolar depression?

Research shows that Accelerated Theta Burst Stimulation (aiTBS), which participants in this trial may receive, works better than sham treatments in reducing depression symptoms in people with bipolar disorder. Studies indicate that aiTBS significantly improves mood in patients who haven't responded to other treatments. This treatment targets the left dorsolateral prefrontal cortex, a specific part of the brain involved in mood control. Early findings suggest that aiTBS can reduce depression symptoms more effectively than sham treatments. Overall, the evidence supports aiTBS as a promising option for those dealing with bipolar depression. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with bipolar depression who haven't improved after at least two different treatments. Participants must score at least 20 on the MADRS depression scale, meet DSM 5 criteria for Bipolar I or II, be able to consent, and pass a safety screen for TMS. They should be on stable medication including one mood stabilizer.

Inclusion Criteria

I am on a consistent medication plan that includes at least one mood stabilizer.

My depression is severe, scoring 20 or more on a scale.

Right or left handed

Exclusion Criteria

No current substance abuse disorder for the past 6 months

Not able to verify contact information

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive high dose spaced theta-burst rTMS or sham treatment for 5 consecutive days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated Theta Burst Stimulation
• Sham Accelerated Theta Burst Stimulation

Trial Overview

The study tests if high dose spaced theta-burst rTMS can significantly reduce depressive symptoms in bipolar disorder compared to sham treatment over five days. It also aims to identify biomarkers in the brain that could predict remission from bipolar depression after treatment.

How Is the Trial Designed?

Group I: Active iTBS Experimental Treatment 1 Intervention

Patients will receive unilateral accelerated theta-burst stimulation to the left dorsal lateral prefrontal cortex for 5 consecutive days, with a total of 10 hours a day. Treatment will be 10min with 50min of breaks in between the 10 sessions.

Group II: Sham iTBS Placebo Group 1 Intervention

Patients will receive sham unilateral accelerated theta-burst stimulation to the left dorsal lateral prefrontal cortex for 5 consecutive days, with a total of 10 hours a day. Treatment will be 10min with 50min of breaks in between the 10 sessions.

Accelerated Theta Burst Stimulation is already approved in United States for the following indications:

Approved in United States as MagVita TMS Therapy System w/Theta Burst Stimulation for:

• Major Depressive Disorder in adult patients who have failed to receive satisfactory improvement from prior antidepressant medication in the current episode

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Milken Institute

Collaborator

Trials

8

Recruited

270+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

In a case series of 9 patients with major depressive disorder and bipolar disorder, accelerated theta-burst rTMS treatment over 8 days led to significant reductions in depression symptoms, as measured by the CES-D and CGI scales.

The treatment was well tolerated, with mild headaches being the most common side effect, and five patients achieving at least a 50% reduction in symptoms by the end of the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated theta-burst repetitive transcranial magnetic stimulation for depression in South Africa. Bröcker, E., van den Heuvel, L., Seedat, S.[2020]

Continuous theta burst stimulation (cTBS) was found to be safe and well-tolerated in patients with major depressive disorder (MDD) or bipolar depression (BD), with no significant differences in adverse events compared to sham treatment.

However, the meta-analysis of three randomized controlled trials involving 78 participants showed no significant improvement in depression scores or response rates with cTBS compared to sham, indicating that cTBS may not provide a therapeutic advantage for treating major depressive episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies. Cai, DB., Qin, XD., Qin, ZJ., et al.[2023]

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]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[2022]

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 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]

Theta-burst stimulation (TBS) shows promise as a rapid and effective treatment for psychiatric disorders, particularly treatment-resistant depression and auditory hallucinations, with studies indicating mild adverse effects but no severe complications like seizures or mania.

The current research on TBS is varied in design and outcomes, highlighting the need for more rigorous sham-controlled studies to better assess its long-term safety and efficacy in treating various psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Theta-Burst Stimulation in the Treatment of Psychiatric Disorders: A Review of the Literature. Rachid, F.[2019]

Theta burst stimulation (TBS) appears to be safe and tolerable for children and adolescents, with reported adverse events mostly being mild, such as headaches, similar to those seen in adults.

Despite the promising safety profile, there is a lack of long-term studies on TBS in younger populations, highlighting the need for further research to better understand its effects and potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Safety and Tolerability of Theta Burst Stimulation in Children and Adolescents. Elmaghraby, R., Sun, Q., Ozger, C., et al.[2023]

In a randomized-controlled trial involving 32 patients with major depression, bilateral theta burst stimulation (TBS) to the dorsolateral prefrontal cortex showed a significant increase in treatment response compared to sham stimulation, with 9 responders in the TBS group versus 4 in the sham group.

The study also indicated a trend towards higher remission rates in the TBS group as measured by the Beck Depression Inventory, suggesting that TBS may enhance the effectiveness of ongoing medication and psychotherapy in treating major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. Plewnia, C., Pasqualetti, P., Große, S., et al.[2018]

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