Transcranial Electrical Stimulation for Bipolar Disorder

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Beth Israel Deaconess Medical Center

Disqualifiers: Substance abuse, Pregnancy, Head injury, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Mania is a core symptom of bipolar disorder involving periods of euphoria. Decreased inhibitory control, increased risk-taking behaviors, and aberrant reward processing are some of the more recognized symptoms of bipolar disorder and are included in the diagnostic criteria for mania. Current drug therapies for mania are frequently intolerable, ineffective, and carry significant risk for side effects. Presently there are no neurobiologically informed therapies that treat or prevent mania. However, using a newly validated technique termed lesion network mapping, researchers demonstrated that focal brain lesions having a causal role in the development of mania in people without a psychiatric history can occur in different brain locations, such as the right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex (DLPFC), and right inferior temporal gyrus (ITG). This lesion network evidence converges with existing cross-sectional and longitudinal observations in bipolar mania that have identified specific disruptions in network communication between the amygdala and ventro-lateral prefrontal cortex. The OFC is associated with inhibitory control, risk-taking behavior, and reward learning which are major components of bipolar mania. Thus, the association between OFC with mania symptoms, inhibitory control, risk-taking behavior, and reward processing suggests that this region could be targeted using non-invasive brain stimulation.

Will I have to stop taking my current medications?

The trial requires that you do not change your mood stabilizing medications for at least 2 weeks before participating. So, you can continue taking your current medications as long as they are stable.

What data supports the effectiveness of this treatment for bipolar disorder?

Research suggests that high-definition transcranial direct current stimulation (HD-tDCS) can modulate brain activity and improve symptoms in psychiatric disorders, indicating potential benefits for bipolar disorder. Additionally, HD-tDCS has been shown to enhance treatment outcomes in other conditions, like post-stroke recovery, by increasing the focus and intensity of the electrical currents used. ^{1 2 3 4 5}

Is transcranial electrical stimulation safe for humans?

Transcranial electrical stimulation (TES), including various forms like tDCS and tACS, is generally considered safe for humans, with no serious adverse events reported in over 18,000 sessions. Mild side effects like headaches and skin sensations are possible, but serious issues are rare, and the treatment is well-tolerated in both healthy and clinical populations. ^{6 7 8 9 10}

How is the treatment Transcranial Electrical Stimulation for Bipolar Disorder different from other treatments?

This treatment is unique because it uses non-invasive electrical currents applied to the scalp to modulate brain activity, potentially improving symptoms by targeting specific brain areas. Unlike traditional medications, it directly influences brain function without systemic side effects. ^{2 3 11 12 13}

Eligibility Criteria

This trial is for adults aged 18-65 with bipolar disorder or schizoaffective disorder, who have experienced mania before and are currently having mild to moderate symptoms. Participants must not have changed their mood stabilizers recently, should not be pregnant or breastfeeding, free from substance abuse in the last six months, and without a history of severe head injury or seizures.

Inclusion Criteria

I have been diagnosed with bipolar disorder or schizoaffective disorder, bipolar type.

Has not recently participated in tES/TMS treatments

Proficient in English

Exclusion Criteria

I have had a head injury with more than 15 minutes of unconsciousness.

I have had seizures in the past.

Pregnant or breastfeeding

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial electrical stimulation targeting the OFC for 5 days, with two 20-minute sessions per day

1 week

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including YMRS, ASRM, and other secondary measures

3 months

Long-term follow-up

Participants' psychiatric hospitalization rates for mania are compared from average per year prior to study entry to 1 year post study completion

1 year

Treatment Details

Interventions

• High-Definition Personalized Beta-Gamma Electrical Stimulation (Transcranial Electrical Stimulation)
• High-Definition Transcranial Alternate-Current Stimulation (Transcranial Electrical Stimulation)
• High-Definition Transcranial Electrical-Current Stimulation (Transcranial Electrical Stimulation)

Trial Overview Researchers are testing three types of non-invasive brain stimulation: High-Definition Transcranial Electrical-Current Stimulation (HD-tES), Alternate-Current Stimulation (HD-tACS), and Personalized Beta-Gamma Electrical Stimulation. These aim to target specific brain areas linked to mania symptoms like euphoria and risk-taking behaviors.

Participant Groups

Group I: Personalized Beta-Gamma tACS Experimental Treatment 1 Intervention

10 tACS; Two, twenty-minute sessions of tACS to the OFC for 5 days (10 total sessions).

Group II: Active HD-tDCS Active Control 1 Intervention

10 tDCS; Two, twenty-minute sessions of tDCS to the OFC for 5 days (10 total sessions).

Group III: Active Control (alpha, 10 Hz) Placebo Group 1 Intervention

10 passive sham control; Two, twenty-minute sessions of passive sham control to the OFC for a 30 second ramped up and down at the beginning and end of the 20 min period for 5 days (10 total sessions).

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Findings from Research

The novel high-definition transcranial direct current stimulation (HD-tDCS) setup was found to be safe and well-tolerated, with fewer adverse effects compared to conventional tDCS, based on a study involving 60 healthy participants.

HD-tDCS significantly improved cognitive performance on a visual task, indicating its potential for more effective neural modulation, while also being compatible with simultaneous fMRI without causing significant heating or image quality issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Blinding Efficacy and Behavioural Effects of a Novel MRI-Compatible, High-Definition tDCS Set-Up. Gbadeyan, O., Steinhauser, M., McMahon, K., et al.[2022]

Transcranial electrical stimulation (TES) can modulate brain activity using low-intensity currents, but the effects observed may not solely be due to the targeted brain region, as peripheral stimulation could also play a significant role.

The review emphasizes the need for careful consideration of TES's biophysical properties and dose-response relationships, suggesting that researchers should control for peripheral effects and be cautious in attributing behavioral changes to specific brain areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can Transcranial Electrical Stimulation Localize Brain Function? Karabanov, AN., Saturnino, GB., Thielscher, A., et al.[2023]

Transcranial direct current stimulation (tDCS) is a promising non-invasive technique that can help relieve symptoms of psychiatric disorders, with evidence showing it induces plastic changes in the brain as detected by EEG and event-related potentials (ERPs).

A systematic review of 21 studies indicates that EEG and ERPs are effective markers for monitoring brain changes and symptom improvement after tDCS, although future research should standardize protocols to enhance the reliability of findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of Electrophysiology by Transcranial Direct Current Stimulation in Psychiatric Disorders: A Systematic Review. Kim, M., Kwak, YB., Lee, TY., et al.[2023]

High-definition transcranial direct current stimulation (HD-tDCS) is feasible and acceptable for patients with chronic post-stroke aphasia, showing that it can be implemented effectively in a clinical setting with similar protocols to conventional sponge-based tDCS.

Preliminary results indicate that HD-tDCS may improve naming accuracy and response time in patients, with some evidence suggesting it could be more effective than conventional tDCS, although the differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of using high-definition transcranial direct current stimulation (HD-tDCS) to enhance treatment outcomes in persons with aphasia. Richardson, J., Datta, A., Dmochowski, J., et al.[2023]

In a study involving 70 healthy males, high-definition transcranial direct current stimulation (HD-tDCS) significantly increased resting-state functional connectivity (rsFC) between the right inferior frontal gyrus and the left prefrontal cortex compared to a sham group, indicating its potential therapeutic effects.

The study found considerable variability in the electric fields induced by HD-tDCS, suggesting that individualized head models are necessary to optimize treatment effects and minimize differences in patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HD-tDCS induced changes in resting-state functional connectivity: Insights from EF modeling. Müller, D., Habel, U., Brodkin, ES., et al.[2023]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

Transcranial electrical stimulation (tES), including tDCS and MHF-tPCS, was found to be well tolerated in healthy subjects over a six-week period, with common side effects being mild skin sensations like tingling and itching, which were less frequent than in the sham-tDCS group.

The MHF-tPCS group showed significantly higher compliance in completing sessions compared to the sham-tDCS group, indicating that this waveform may be more acceptable for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects. Paneri, B., Adair, D., Thomas, C., et al.[2018]

A high-resolution multi-layer skin model was developed to better predict current flow during transcranial electrical stimulation (tES), revealing that current concentration remains annular around electrode edges despite realistic tissue parameters.

The model demonstrated that adding structures like sweat glands and blood vessels can help distribute current more evenly, which aligns with experimental observations of skin reactions, such as erythema, during tES.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of skin tissue layers and ultra-structure in transcutaneous electrical stimulation including tDCS. Khadka, N., Bikson, M.[2022]

A systematic review of 64 studies involving 2262 participants found that transcranial direct current stimulation (tDCS) has a low dropout rate (6% for active and 7.2% for sham), indicating good acceptability among participants.

Despite the low dropout rates, many studies inadequately reported adverse events (AEs), highlighting a need for improved guidelines to standardize AE reporting in tDCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. Aparício, LVM., Guarienti, F., Razza, LB., et al.[2018]

A case study of a 33-year-old woman with bipolar II disorder revealed that transcranial direct current stimulation (tDCS) using a frontoextracephalic configuration induced hypomania, while a previous tDCS treatment with a bifrontal montage did not cause such symptoms.

This suggests that while frontoextracephalic tDCS may have antidepressant effects, it could also pose risks for inducing hypomanic symptoms in bipolar patients, indicating a need for caution and further investigation into its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypomania induction in a patient with bipolar II disorder by transcranial direct current stimulation (tDCS). Gálvez, V., Alonzo, A., Martin, D., et al.[2011]

Transcranial direct current stimulation (tDCS) applied to the prefrontal and cerebellar regions significantly improved neuropsychological functioning in 25 euthymic patients with bipolar disorder over a 3-week period.

Patients demonstrated notable enhancements in visuospatial memory and executive functioning, particularly those with initially poorer cognitive performance, suggesting that tDCS may effectively modulate disrupted brain circuits in bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefronto-cerebellar transcranial direct current stimulation improves visuospatial memory, executive functions, and neurological soft signs in patients with euthymic bipolar disorder. Minichino, A., Bersani, FS., Bernabei, L., et al.[2020]

Transcranial direct current stimulation (tDCS) appears to be well tolerated and safe for children and adolescents with various psychiatric disorders, based on a review of six studies, including three randomized clinical trials.

However, due to the limited number of studies and the need for more rigorous research, definitive conclusions about its efficacy compared to standard treatments cannot yet be made.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation in Child and Adolescent Psychiatry. Muszkat, D., Polanczyk, GV., Dias, TG., et al.[2018]

References

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

Safety, Tolerability, Blinding Efficacy and Behavioural Effects of a Novel MRI-Compatible, High-Definition tDCS Set-Up. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Can Transcranial Electrical Stimulation Localize Brain Function? [2023]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Modulation of Electrophysiology by Transcranial Direct Current Stimulation in Psychiatric Disorders: A Systematic Review. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Feasibility of using high-definition transcranial direct current stimulation (HD-tDCS) to enhance treatment outcomes in persons with aphasia. [2023]

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

HD-tDCS induced changes in resting-state functional connectivity: Insights from EF modeling. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. [2023]

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

Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects. [2018]

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

Role of skin tissue layers and ultra-structure in transcutaneous electrical stimulation including tDCS. [2022]

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

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. [2020]

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

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]

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

Hypomania induction in a patient with bipolar II disorder by transcranial direct current stimulation (tDCS). [2011]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Prefronto-cerebellar transcranial direct current stimulation improves visuospatial memory, executive functions, and neurological soft signs in patients with euthymic bipolar disorder. [2020]

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

Transcranial Direct Current Stimulation in Child and Adolescent Psychiatry. [2018]