TMS for Depression

Overseen By Camilla Whitesel

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Pennsylvania

Must not be taking: Lithium, Antipsychotics, MAOIs, others

Disqualifiers: Psychosis, Substance use disorder, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to investigate the responses of the brain region known as the subgenual anterior cingulate cortex (sgACC) during transcranial magnetic stimulation (TMS) in individuals with depression. Specifically, investigators aim to determine whether the sgACC is engaged when TMS is delivered to specific targets and if the engagement of sgACC changes throughout a full TMS treatment intervention. To achieve this goal, the investigators will employ a combination of TMS and Magnetic Resonance Imaging (MRI) procedures. Study participation will include completing various questionnaires, clinical assessments, receiving a full transcranial magnetic stimulation (TMS) treatment intervention (every weekday for 6 weeks), and undergoing MRI scans, both with and without concurrent TMS.

Will I have to stop taking my current medications?

You may need to stop some medications. While SSRIs and SNRIs are allowed, you cannot take lithium, antipsychotics, TCAIs, MAOIs, or atypical antidepressants. Benzodiazepines must be stopped 24 hours before visits, and Bupropion above 350 mg is not allowed.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation (TMS) for depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, and a newer form called theta burst stimulation (TBS) has shown similar effectiveness with shorter treatment times. Studies suggest TBS can be a good alternative for those who do not respond to traditional treatments. ^{1 2 3 4 5}

Is TMS safe for treating depression?

Research shows that TMS, including its variations like rTMS and TBS, is generally safe and well-tolerated in treating depression. Studies indicate that increasing the intensity of TBS does not lead to more side effects, and the incidence of adverse events is similar to standard TMS treatments. ^{1 6 7 8 9}

How is TMS treatment for depression different from other treatments?

TMS (Transcranial Magnetic Stimulation) is unique because it uses magnetic fields to stimulate nerve cells in the brain, which is different from medications that work chemically. Variations like Theta Burst Stimulation (TBS) offer shorter treatment times and potentially improved efficiency, making it a novel option compared to traditional therapies. ^{1 2 10 11 12}

Eligibility Criteria

This trial is for individuals with various forms of depression, including persistent depressive disorder and major depressive disorder. Participants must be eligible to undergo MRI scans and receive daily TMS treatments on weekdays for 4-6 weeks.

Inclusion Criteria

Patient Health Questionnaire-9 (PHQ-9) score greater than or equal to 10

Comprehension of instructions in the English language

Availability for the duration of the study

Exclusion Criteria

Implanted devices, such as an aneurysm clip or cardiac pacemaker

Current psychosis, mania, or substance use disorder

I have a history of a serious neurological disorder or traumatic brain injury.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline TMS/fMRI

Participants undergo an MRI scan to generate individualized TMS targets and complete the first TMS/fMRI session

1 week

1 visit (in-person)

Treatment

Participants receive rTMS treatments daily (Monday to Friday) for 6 weeks and complete various surveys

6 weeks

30 visits (in-person)

Follow-up

Remote follow-up assessments at 1, 6, and 12 months post-treatment to evaluate enduring improvements in clinical symptoms

12 months

3 visits (virtual)

Treatment Details

Interventions

• Transcranial Magnetic Stimulation (TMS) (Behavioural Intervention)

Trial Overview The study is testing how a brain region called the subgenual anterior cingulate cortex (sgACC) responds to Transcranial Magnetic Stimulation (TMS). It involves daily TMS sessions combined with MRI scans to observe changes in sgACC engagement during treatment.

Participant Groups

Group I: Anticorrelation Target Active Control 1 Intervention

TMS treatment will be administered using a TMS target anticorrelated with the sgACC.

Group II: Positive Correlation Target Active Control 1 Intervention

TMS treatment will be administered using a TMS target positively correlated with the sgACC.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), has been shown to be effective in treating major depression, with a response rate effect size of 0.38 and a remission rate effect size of 0.20 based on a meta-analysis of 10 studies involving 591 participants.

TBS is not only effective but also has a favorable safety profile, showing no major adverse events, and is more efficient in terms of time and energy compared to standard rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of theta-burst stimulation for major depression: A systematic review and meta-analysis. Chu, HT., Cheng, CM., Liang, CS., et al.[2021]

In a study of 58 primarily treatment-resistant depressed patients, bilateral neuronavigated theta burst stimulation (TBS-20Hz) achieved a remission rate of 72%, indicating its potential effectiveness in treating difficult cases of depression.

Patients experienced an average 81% reduction in depression scores within about 7.3 weeks, with 40% of those who achieved remission able to discontinue one or more of their previous medications, suggesting TBS-20Hz could be a significant advancement in depression treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral neuronavigated 20Hz theta burst TMS for treatment refractory depression: An open label study. Stubbeman, WF., Zarrabi, B., Bastea, S., et al.[2019]

Intermittent theta burst stimulation (iTBS) is a cost-effective alternative to conventional 10Hz rTMS for treating depression, with an average treatment cost of $1,108 compared to $1,844 for 10Hz rTMS, resulting in savings of $735 per patient.

iTBS also shows a lower average cost per remission at $3,695, compared to $6,146 for 10Hz rTMS, leading to significant savings of $2,451 per remission, making it a more efficient treatment option in healthcare systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of intermittent theta burst stimulation compared to conventional repetitive transcranial magnetic stimulation in patients with treatment resistant depression: A cost analysis. Mendlowitz, AB., Shanbour, A., Downar, J., et al.[2020]

Theta burst stimulation (TBS), a novel form of repetitive transcranial magnetic stimulation (rTMS), shows promise as an effective treatment for major depression, with evidence supporting its non-inferiority to traditional rTMS based on a systematic review of studies.

TBS has demonstrated antidepressant effects and is considered a viable alternative for treatment-resistant depression, although further research is needed to fully understand its physiological effects and optimize treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is theta burst stimulation ready as a clinical treatment for depression? Chen, L., Chung, SW., Hoy, KE., et al.[2020]

In a randomized controlled trial involving 56 patients with moderate to severe depression, bilateral theta-burst stimulation (TBS) and repetitive transcranial magnetic stimulation (rTMS) did not show significant improvements in depression scores compared to sham treatment.

However, there was a noted tendency for both active treatments to increase the responder rate, particularly for the TBS group, suggesting that further research may be needed to explore its potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. Prasser, J., Schecklmann, M., Poeppl, TB., et al.[2015]

Repetitive transcranial magnetic stimulation (rTMS) is generally a well-tolerated treatment for depression, with mild side effects like headaches being the most common, while severe adverse effects are rare.

Special precautions are necessary for certain groups, such as adolescents, pregnant women, and individuals with metal implants, but with proper assessment and monitoring, rTMS can be safely administered to many patients with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. Taylor, R., Galvez, V., Loo, C.[2019]

In a study of 165 pediatric participants aged 6 to 18, theta-burst TMS (TBS) demonstrated a similar safety profile to single- and paired-pulse TMS (sp/ppTMS), with no severe adverse effects reported.

The overall rate of adverse effects was 10.5% for TBS and 12.4% for sp/ppTMS, with most effects rated as minimal or mild, indicating that TBS is a safe option for further investigation in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. Hong, YH., Wu, SW., Pedapati, EV., et al.[2020]

Theta-burst transcranial magnetic stimulation (TBS) is safe and well tolerated in patients with major depression, based on a study involving 33 participants over 10 consecutive days.

The study suggests that TBS may have antidepressant effects, and increasing stimulation parameters does not lead to more side effects, potentially enhancing its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. Chistyakov, AV., Rubicsek, O., Kaplan, B., et al.[2019]

Theta burst stimulation (TBS) is significantly more effective than sham treatment for patients with major depressive disorder (MDD), based on a meta-analysis of 10 randomized controlled trials involving 667 patients, with a response rate indicating a strong effect.

TBS shows similar efficacy to standard high-frequency rTMS, with no significant difference in response rates or adverse events, suggesting it is a viable alternative treatment for MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta burst stimulation for the acute treatment of major depressive disorder: A systematic review and meta-analysis. Voigt, JD., Leuchter, AF., Carpenter, LL.[2021]

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 small study of six patients with resistant depression who had previously undergone electroconvulsive therapy (ECT), deep transcranial magnetic stimulation (TMS) showed potential efficacy, with two patients responding to treatment, including one achieving full remission.

The study suggests that deep TMS may benefit a specific group of patients who did not respond to ECT, but emphasizes the need for larger studies to confirm these findings due to the small sample size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to deep TMS in depressive patients with previous electroconvulsive treatment. Rosenberg, O., Zangen, A., Stryjer, R., et al.[2016]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of theta-burst stimulation for major depression: A systematic review and meta-analysis. [2021]

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

Bilateral neuronavigated 20Hz theta burst TMS for treatment refractory depression: An open label study. [2019]

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

Implementation of intermittent theta burst stimulation compared to conventional repetitive transcranial magnetic stimulation in patients with treatment resistant depression: A cost analysis. [2020]

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

Is theta burst stimulation ready as a clinical treatment for depression? [2020]

5. England pubmed.ncbi.nlm.nih.gov

Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. [2020]

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

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. [2019]

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

Theta burst stimulation for the acute treatment of major depressive disorder: A systematic review and meta-analysis. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Response to deep TMS in depressive patients with previous electroconvulsive treatment. [2016]

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

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