Transcranial Magnetic Stimulation for Bipolar Disorder

Overseen By Alexis Worthley, BA

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Psychiatric disorders, Substance abuse, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how transcranial magnetic stimulation (TMS) might help people with bipolar disorder manage their emotions better. TMS is a non-invasive procedure that uses magnetic fields to stimulate brain nerve cells. The trial includes two groups: one with individuals diagnosed with bipolar disorder and a control group with no psychiatric issues. It seeks participants with bipolar disorder who currently feel emotionally stable but have struggled with emotion regulation.

As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance emotional regulation strategies for those with bipolar disorder.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that your medication has been stable for at least 3 months before participating.

What prior data suggests that transcranial magnetic stimulation is safe for individuals with bipolar disorder?

Research has shown that transcranial magnetic stimulation (TMS) is generally safe for people with bipolar disorder. Studies indicate that it works well and is tolerated by those with bipolar depression that hasn't improved with other treatments. In these studies, participants experienced positive results from TMS without serious side effects.

One study found that TMS is just as safe for people with bipolar disorder as for those with unipolar depression. This suggests that people with bipolar disorder can expect similar safety when using TMS. Overall, research suggests that TMS is a safe option for managing symptoms of bipolar disorder. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcranial Magnetic Stimulation (TMS) for bipolar disorder because it offers a non-invasive approach that targets the brain directly with magnetic pulses. Unlike standard treatments like mood stabilizers, antipsychotics, and antidepressants, which work through chemical changes in the brain, TMS stimulates specific brain regions involved in mood regulation. This method might have fewer side effects and could potentially provide quicker symptom relief. By focusing on the brain's circuitry, TMS represents a promising alternative for those who may not respond to or tolerate traditional medications.

What evidence suggests that transcranial magnetic stimulation is effective for bipolar disorder?

Research has shown that transcranial magnetic stimulation (TMS) can help treat bipolar depression. TMS is already approved for major depression and has shown promise in real-world studies for bipolar disorder as well. In this trial, participants with bipolar disorder will receive either high-dose TMS or sham TMS. Some studies suggest TMS might benefit people with treatment-resistant bipolar depression, meaning those who haven't responded well to other treatments. However, results have been mixed, and more research is needed to confirm its effectiveness for bipolar disorder. Overall, TMS is considered a hopeful option for managing mood symptoms in bipolar disorder. ^{1 4 6 7 8}

Who Is on the Research Team?

Kristen Ellard, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with bipolar mood disorders who struggle to regulate their emotions. Healthy individuals without psychiatric conditions, as confirmed by an interview, and who score below 80 on the Emotion Regulation Scale can also participate.

Inclusion Criteria

You have never been diagnosed with a mental health disorder after being assessed with the MINI.

Your ability to manage and control your emotions will be assessed using a scale called the DERS. If you score less than 80 on this scale, it means that you have normal levels of emotion regulation.

Requirements for people who are healthy and will be used as a comparison group in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 - Control Group Assessment

Healthy control subjects undergo fMRI scanning while performing emotion regulation tasks to establish a normative sample.

2 weeks

1 visit (in-person)

Phase 2 - Patient Group Assessment and Treatment

Patients with bipolar disorder perform emotion regulation tasks during fMRI scanning, followed by TMS sessions targeting individualized brain regions.

2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after TMS treatment, with assessments of behavior, neural activation, and functional connectivity.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TMS

Trial Overview The study is testing whether Transcranial Magnetic Stimulation (TMS), a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain, can improve emotion regulation in people with bipolar disorder.

How Is the Trial Designed?

Group I: Bipolar Group Experimental Treatment 1 Intervention

This group consists of individuals with a diagnosis of bipolar disorder who have been randomized to receive high-dose TMS (i.e., 1800 pulses) and sham TMS.

Group II: Healthy Control Active Control 1 Intervention

This group consists of individuals with no psychiatric diagnosis.

TMS is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Approved in European Union as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Approved in Canada as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Repetitive transcranial magnetic stimulation (rTMS) has shown a higher clinical response rate in treating bipolar depression compared to sham treatment, with an odds ratio of 2.72 based on data from 274 patients across 14 studies.

Significant clinical response was specifically noted with high-frequency rTMS targeting the left dorsolateral prefrontal cortex, indicating a potential effective treatment approach, although more large-scale studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of repetitive transcranial magnetic stimulation (rTMS) for bipolar depression: A systematic review and meta-analysis. Nguyen, TD., Hieronymus, F., Lorentzen, R., et al.[2021]

In a study of 40 patients with mixed episodes of bipolar disorder, low-frequency rTMS (1Hz) applied to the right Dorsolateral Prefrontal Cortex showed a 46.6% responder rate for depressive symptoms, with 28.6% achieving remission.

The treatment also demonstrated a 15% responder rate for manic symptoms, indicating that LF-rTMS may be an effective augmentation strategy for managing both depressive and manic symptoms in mixed states of bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS in resistant mixed states: an exploratory study. Pallanti, S., Grassi, G., Antonini, S., et al.[2018]

In a follow-up study of 11 drug-resistant depressed bipolar patients, those who achieved remission after acute rTMS treatment were more likely to maintain their improvement after one year, indicating the long-term efficacy of rTMS.

Conversely, patients who did not respond to rTMS initially were unlikely to experience any long-term benefits, suggesting that early response is crucial for predicting sustained outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy after acute augmentative repetitive transcranial magnetic stimulation in bipolar depression: a 1-year follow-up study. Dell'osso, B., D'Urso, N., Castellano, F., et al.[2022]

In a study of 105 patients with major depressive disorder (MDD) treated with Transcranial Magnetic Stimulation (TMS), those with bipolar diathesis (soft signs of bipolarity) had similar response rates to TMS as those without, indicating that TMS is safe for this group.

However, the remission rate was lower for patients with bipolar soft signs (13.5%) compared to those without (30.2%), suggesting that while TMS is safe, it may be less effective for achieving remission in patients with these soft signs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do bipolar disorder soft signs impact outcomes following Transcranial Magnetic Stimulation (TMS) therapy for depression? Bennett, E., Almeida, JRC., Carpenter, LL.[2020]

A study of 505 patients treated with repetitive transcranial magnetic stimulation (rTMS) found that both bipolar and unipolar patients with depression responded similarly to the treatment, indicating rTMS is effective for both groups.

Interestingly, bipolar patients showed a significant improvement in paranoid symptoms compared to unipolar patients, suggesting rTMS may be particularly beneficial for this specific symptom in bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Repetitive Transcranial Magnetic Stimulation in the Treatment of Bipolar Disorder in Comparison to the Treatment of Unipolar Depression in a Naturalistic Setting. Alhelali, A., Almheiri, E., Abdelnaim, M., et al.[2022]

A review of 34 studies involving 611 patients suggests that repetitive transcranial magnetic stimulation (rTMS) may reduce symptoms of bipolar disorder, particularly in bipolar depression, but its efficacy compared to sham treatment is not clearly established in randomized controlled trials.

Reported side effects of rTMS include headache, dizziness, and sleep problems, with some cases of affective switching noted, although no specific risk factors for this were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation in the Treatment of Bipolar Disorder. Hett, D., Marwaha, S.[2023]

A systematic review of 31 studies on repetitive transcranial magnetic stimulation (rTMS) in bipolar disorder (BD) found that while rTMS is generally safe and well tolerated, the evidence for its efficacy is limited and mixed, particularly in bipolar depressive episodes.

There is a need for larger, well-designed clinical trials to better understand the effectiveness of rTMS in various stages of BD, including manic and mixed episodes, as well as its potential for mood stabilization and reducing suicidal behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) in bipolar disorder: A systematic review. Konstantinou, G., Hui, J., Ortiz, A., et al.[2023]

A case study demonstrated that low-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral pre-frontal cortex significantly improved symptoms in a drug-resistant bipolar depression patient over a 3-week treatment period, as measured by multiple depression rating scales.

The patient maintained therapeutic benefits for an additional 6 months with periodic maintenance rTMS sessions, suggesting that rTMS could be an effective treatment option for managing bipolar depression, although further controlled studies are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentative transcranial magnetic stimulation (TMS) combined with brain navigation in drug-resistant rapid cycling bipolar depression: a case report of acute and maintenance efficacy. Dell'osso, B., Altamura, AC.[2009]

Repetitive transcranial magnetic stimulation (rTMS) was found to be safe for treating depressive symptoms in 23 patients with bipolar affective disorder (BPAD), with no significant adverse events or induction of mania during the 2-week study.

While rTMS showed a trend towards improved mood ratings compared to placebo, the study did not find statistically significant differences in antidepressant response rates or overall depression scores, indicating that further research is needed to clarify its efficacy in BPAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy. Nahas, Z., Kozel, FA., Li, X., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33949063/

Repetitive transcranial magnetic stimulation (rTMS) in ... Most studies included participants diagnosed with a bipolar depressive episode (N = 24), have yielded mixed findings, and have yet to reach a consensus on the ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2667174325001727

Efficacy, effectiveness and safety of transcranial magnetic ... Repetitive transcranial magnetic stimulation (rTMS) is FDA-approved for major depression and recently received breakthrough status for bipolar ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33074144/

The efficacy of repetitive transcranial magnetic stimulation ... rTMS seems effective in the treatment of bipolar depression, but dedicated and adequately powered RCTs are needed in order to firmly conclude that rTMS should ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00186485

Repetitive Transcranial Magnetic Stimulation (rTMS) for ... The primary objective of this study is to examine the safety and efficacy of rTMS in the management of treatment-resistant bipolar depression.

5. sciencedirect.com sciencedirect.com/science/article/pii/S240584402403319X

Real-world retrospective study of repetitive transcranial ... This retrospective study, using real-world TMS registry data, suggests that rTMS treatment for BD could be as effective as that for unipolar depression.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6790310/

Clinical applications of transcranial magnetic stimulation in ... Cognitive outcomes of TMS treatment in bipolar depression: Safety data from a randomized controlled trial. Journal of Affective Disorders, 235, 20–26.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35772133/

The Efficacy and Safety of Transcranial Magnetic ... Conclusions: The results of our study showed that TMS treatment is an effective and safe treatment for patients with treatment-resistant bipolar depression.

8. nature.com nature.com/articles/s41380-023-02045-8

Repetitive transcranial magnetic stimulation for bipolar ... The outcomes were treatment response (primary), improvement in depressive symptoms, remission rate, all-cause discontinuation, and mania ...