Accelerated TMS for Depression and OCD

Overseen By Lindsay Victoria, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Weill Medical College of Cornell University

Disqualifiers: Suicide risk, Substance use disorder, Neurological disorder, 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: Unknown

Duration: 5-10 days

500 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new, faster treatment for people with depression and OCD. The goal is to see if this approach can quickly improve symptoms. The study also uses brain scans to find markers that predict who will benefit most from the treatment. This method has shown effectiveness in treating depression and cognitive impairment, and is being explored for its potential in treating OCD.

Will I have to stop taking my current medications?

You may not need to stop your current medications. If you are on antidepressants, you can continue them if your dose has been stable for at least four weeks. Other medications will be reviewed by a specialist to ensure they are safe to use with the treatment.

What data supports the effectiveness of the treatment Accelerated TMS for Depression and OCD?

Research shows that continuous theta burst stimulation (a type of TMS) can reduce symptoms in patients with OCD who haven't responded to other treatments. Studies have found improvements in anxiety and overall severity of symptoms, suggesting that TMS may help modulate brain activity linked to OCD. ^{1 2 3 4 5}

Is accelerated TMS safe for humans?

Accelerated TMS, including theta-burst stimulation, is generally safe for humans, with mild headaches being the most commonly reported side effect. In studies, it was well tolerated by most participants, although some experienced tolerability issues. ^{6 7 8 9 10}

How is Accelerated TMS treatment different from other treatments for depression and OCD?

Accelerated TMS (Transcranial Magnetic Stimulation) is unique because it uses a rapid schedule of theta-burst stimulation, which is a patterned form of magnetic pulses, to treat depression and OCD. This approach allows for shorter treatment sessions over a condensed period, potentially leading to quicker symptom relief compared to traditional TMS or medication. ^{6 7 8 10 11}

Research Team

Conor Liston, MD, PhD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for adults with major depression or OCD who haven't improved after trying at least one medication. They must be stable on their current antidepressants, if any, and able to consent. People with psychotic symptoms, recent substance abuse, significant neurological disorders, imminent suicide risk, or other primary psychiatric diagnoses besides OCD or mild anxiety are excluded.

Inclusion Criteria

I am not on antidepressants or have been on a stable dose for 4+ weeks.

I am able to understand and agree to the study's procedures and risks.

I have been diagnosed with major depression or OCD.

Exclusion Criteria

I have a history of seizures or take medication that could increase my risk of seizures.

I do not have symptoms that would affect my understanding of the trial.

I started psychotherapy within the last 8 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 5-day course of rTMS delivered hourly for 10 hours per day, targeting either the LPFC or DMPFC. Non-responders may receive a second 5-day course targeting the opposite brain area.

5-10 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including clinical assessments and fMRI scans.

4 weeks

Treatment Details

Interventions

• Accelerated TMS

Trial Overview The study tests an accelerated 5-day rTMS treatment using the MagVenture MagPro System aimed at rapidly improving depression and OCD symptoms. Participants will undergo fMRI scans to find biomarkers predicting TMS benefits. They'll receive intense daily rTMS sessions targeting specific brain areas over a week, possibly followed by another course if partially responsive.

Participant Groups

Group I: OCD - DMPFC target to (for non-responders) LPFC target Experimental Treatment 1 Intervention

Participants with OCD will receive a 5-day course of rTMS delivered to the DMPFC.Participants may have the option to be crossed over to receive rTMS targeting the opposite brain area (LPFC), enabling us to test whether participants who do not respond well to one target might respond to stimulation of another target. The option to offer a second course of treatment will be based on clinical judgement and re-evaluation of the participant.

Group II: Depression - DMPFC target to (for non-responders) LPFC target Experimental Treatment 1 Intervention

Participants with treatment resistant depression will receive a 5-day course of rTMS delivered to the DMPFC. Participants may have the option to be crossed over to receive rTMS targeting the opposite brain area (LPFC), enabling us to test whether participants who do not respond well to one target might respond to stimulation of another target. The option to offer a second course of treatment will be based on clinical judgement and re-evaluation of the participant.

Group III: Depression - LPFC target to (for non-responders) DMPFC target Active Control 1 Intervention

Participants with treatment resistant depression will receive a 5-day course of rTMS delivered to the LPFC. Participants may have the option to be crossed over to receive rTMS targeting the opposite brain area (DMPFC), enabling us to test whether participants who do not respond well to one target might respond to stimulation of another target. The option to offer a second course of treatment will be based on clinical judgement and re-evaluation of the participant.

Group IV: OCD - LPFC target to (for non-responders) DMPFC target Active Control 1 Intervention

Participants with OCD will receive a 5-day course of rTMS delivered to the LPFC. Participants may have the option to be crossed over to receive rTMS targeting the opposite brain area (DMPFC), enabling us to test whether participants who do not respond well to one target might respond to stimulation of another target. The option to offer a second course of treatment will be based on clinical judgement and re-evaluation of the participant.

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

Approved in United States as rTMS for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in European Union as rTMS for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in United Kingdom as rTMS for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder
• Post-Traumatic Stress Disorder
• Depersonalization Disorder
• Borderline Personality Disorder
• Addiction

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

The Wellcome Leap Fund

Collaborator

Trials

1

Recruited

500+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

The New Venture Fund / Foundation for OCD Research

Collaborator

Trials

1

Recruited

500+

Findings from Research

In a study involving 30 treatment-resistant OCD patients, continuous theta burst transcranial magnetic stimulation (cTBS) over the supplementary motor area was found to be safe but did not significantly improve OCD symptoms compared to sham treatment.

Both active and sham cTBS groups showed similar responder rates (28% for cTBS vs. 36% for sham) at both the end of treatment and follow-up, indicating that cTBS may not be an effective intervention for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous theta burst stimulation over the supplementary motor area in refractory obsessive-compulsive disorder treatment: A randomized sham-controlled trial. Harika-Germaneau, G., Rachid, F., Chatard, A., et al.[2020]

A retrospective analysis of six patients with treatment-resistant OCD showed that continuous theta burst stimulation (cTBS) targeting the supplementary motor cortex may help reduce obsessive-compulsive symptoms, suggesting a potential new treatment avenue.

Despite the promising results, the study highlights the need for further research through randomized, sham-controlled trials with larger participant groups to validate the efficacy of cTBS for OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case Series of Continuous Theta Burst Stimulation Treatment for the Supplementary Motor Area Twice a Day in Patients with Obsessive-Compulsive Disorder: A Real World TMS Registry Study in Japan. Noda, Y., Fujii, K., Tokura, F., et al.[2023]

In a study involving 33 OCD patients, continuous Theta Burst Stimulation (cTBS) targeting the orbitofrontal cortex (OFC) was found to be well tolerated and led to significant improvements in anxiety symptoms and overall severity of OCD after 10 treatment sessions.

While the treatment showed a notable effect on anxiety and global severity scores, the improvements in obsessive and compulsive symptoms were not statistically significant when controlling for other variables, suggesting that the primary benefit of cTBS may be in reducing anxiety associated with OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of intensive orbitofrontal continuous Theta Burst Stimulation (iOFcTBS) in Obsessive Compulsive Disorder: A Randomized Placebo Controlled Study. Dutta, P., Dhyani, M., Garg, S., et al.[2021]

In a pilot study involving 29 OCD patients, continuous theta burst stimulation (cTBS) targeting the bilateral supplementary motor area significantly relieved OCD symptoms in 37.93% of participants, indicating its potential efficacy as a treatment.

The study found that functional connectivity between specific brain regions could predict the effectiveness of cTBS, with a high area under the curve (AUC) of 0.85, suggesting that neuroimaging may help identify which patients are more likely to benefit from this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The functional connectivity predictor of therapeutic effect of continuous theta burst stimulation on obsessive-compulsive disorder: A preliminary study. Li, P., Cheng, J., Fan, Q., et al.[2022]

An 18-year-old female with treatment-refractory obsessive-compulsive disorder (OCD) showed significant symptom improvement after receiving combined repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation targeting the bilateral dorsolateral prefrontal cortex and supplementary motor area.

This case suggests that using a sequential stimulation approach to target different brain regions may enhance the effectiveness of rTMS therapy for patients with OCD, indicating a potential new strategy for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Three Brain Regions (Bilateral SMA, Left and Right DLPFC) Sequentially in One Session Using Combined Repetitive Transcranial Magnetic Stimulation and Intermittent Theta-burst Stimulation in Treatment-refractory Obsessive-compulsive Disorder: A Case Report. Chou, PH., Sack, AT., Su, KP.[2022]

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., et al.[2022]

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]

In a study involving 300 patients with treatment-resistant depression, accelerated bilateral theta burst stimulation (TBS) was found to be effective and safe, with a treatment response rate of 43.7% and a remission rate of 28.2%.

The study revealed no significant differences in efficacy between different TBS intensities or when compared to traditional unilateral 10 Hz rTMS, indicating that the accelerated TBS does not provide faster antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. Chen, L., Thomas, EHX., Kaewpijit, P., et al.[2022]

In a clinical trial involving patients with treatment-resistant depression, both 10 Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) effectively reduced suicidality, with remission rates of 43.7% and 49.1% respectively, showing no significant difference between the two methods.

There was a strong correlation between reductions in suicidality and overall depression severity, indicating that improvements in suicidal thoughts were linked to greater decreases in depressive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of high frequency versus theta-burst repetitive transcranial magnetic stimulation on suicidality in patients with treatment-resistant depression. Mehta, S., Downar, J., Mulsant, BH., et al.[2023]

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]

In a study of 54 patients with major depression, the combination of intermittent theta burst stimulation (iTBS) and low-frequency rTMS (LF-rTMS) significantly improved depression and anxiety symptoms more than high-frequency rTMS (HF-rTMS).

The results suggest that iTBS combined with LF-rTMS may be a promising alternative therapy for major depression, offering both efficacy and time-saving benefits compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left intermittent theta burst stimulation combined with right low-frequency rTMS as an additional treatment for major depression: A retrospective study. Mi, Y., Ji, Y., Lou, Z., et al.[2022]

References

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

Continuous theta burst stimulation over the supplementary motor area in refractory obsessive-compulsive disorder treatment: A randomized sham-controlled trial. [2020]

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

A Case Series of Continuous Theta Burst Stimulation Treatment for the Supplementary Motor Area Twice a Day in Patients with Obsessive-Compulsive Disorder: A Real World TMS Registry Study in Japan. [2023]

3. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy of intensive orbitofrontal continuous Theta Burst Stimulation (iOFcTBS) in Obsessive Compulsive Disorder: A Randomized Placebo Controlled Study. [2021]

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

The functional connectivity predictor of therapeutic effect of continuous theta burst stimulation on obsessive-compulsive disorder: A preliminary study. [2022]

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

Targeting Three Brain Regions (Bilateral SMA, Left and Right DLPFC) Sequentially in One Session Using Combined Repetitive Transcranial Magnetic Stimulation and Intermittent Theta-burst Stimulation in Treatment-refractory Obsessive-compulsive Disorder: A Case Report. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. [2018]

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

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. [2022]

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

Effect of high frequency versus theta-burst repetitive transcranial magnetic stimulation on suicidality in patients with treatment-resistant depression. [2023]

10. South Africa pubmed.ncbi.nlm.nih.gov

Accelerated theta-burst repetitive transcranial magnetic stimulation for depression in South Africa. [2020]

11. India pubmed.ncbi.nlm.nih.gov

Left intermittent theta burst stimulation combined with right low-frequency rTMS as an additional treatment for major depression: A retrospective study. [2022]