Neuromodulation for Depression

(TREND Trial)

Overseen By Study Coordinator

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Erika Forbes

Must not be taking: Clozapine, Bupropion, Stimulants, Benzodiazepines

Disqualifiers: Bipolar, Psychosis, Seizures, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: 10

Duration: 2 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators will administer theta burst stimulation (TBS) in efforts to observe a decrease in severity of reported depression symptoms. A subset of participants will receive positive affect training during this intervention.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. The trial excludes participants who are currently using Clozapine, Bupropion, prescription stimulants, benzodiazepines, or mood stabilizers.

What data supports the effectiveness of the treatment Theta Burst Stimulation (TBS) for depression?

Research shows that Theta Burst Stimulation (TBS), a type of transcranial magnetic stimulation, can be effective for treating depression, especially in patients who have not responded to other treatments. In one study, about 28% of patients achieved remission, and 52% showed significant improvement, indicating that TBS can be a promising option for treatment-resistant depression. ^{1 2 3 4 5}

Is theta burst stimulation (TBS) safe for humans?

Research shows that theta burst stimulation (TBS), a type of brain stimulation, is generally safe and well-tolerated in people with depression. Some participants experienced mild headaches, but no serious side effects were reported. ^{1 4 6 7 8}

How is Theta Burst Stimulation (TBS) different from other treatments for depression?

Theta Burst Stimulation (TBS) is a unique form of transcranial magnetic stimulation (TMS) that uses short bursts of magnetic pulses to stimulate the brain, potentially offering faster and more targeted treatment for depression compared to traditional TMS. It can be administered in accelerated schedules and has different protocols like intermittent (iTBS) and continuous (cTBS), which may enhance its effectiveness and convenience. ^{1 3 4 8 9}

Research Team

Erika E Forbes, Ph.D

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for individuals with a current diagnosis of depression according to the DSM-5. Participants should not have used certain drugs like cocaine or MDMA recently, have high-risk suicidality, severe substance use disorders, specific medication usage (Clozapine, Bupropion), daily nicotine use, or a history of seizures and other listed conditions.

Inclusion Criteria

You are currently diagnosed with Depressive Disorder according to DSM-5.

Exclusion Criteria

You have consumed a large amount of alcohol within the past week or within the last 12 hours.

You have a mental health condition called obsessive-compulsive disorder, which you have had at any point in your life.

You have a history of mental illness that included losing touch with reality.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete a baseline assessment before starting treatment

1 day

Treatment

Participants receive 20 theta burst stimulation (TBS) sessions over 2 weeks, with sessions delivered twice/day, 5 days/week

2 weeks

10 visits (in-person)

Post-TBS Assessment

Participants complete an assessment after the TBS treatment sessions

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a follow-up assessment 4 months later

4 months

Treatment Details

Interventions

• Theta Burst Stimulation

Trial Overview The TREND study is testing theta burst stimulation (TBS) as a treatment for depression. Some participants will also receive positive affect training alongside TBS to see if it helps reduce the severity of depression symptoms more effectively.

Participant Groups

Group I: TBS Experimental Treatment 1 Intervention

In this open-label trial, all participants will undergo 2 continuous TBS (cTBS) sessions per visit over 10 days (weekdays, over 2 weeks; total = 20 TBS sessions in 10 visits). The total time of each pair of sessions (including pause between sessions) will be approximately 1 hour, with each session lasting approximately 100 seconds. There is only 1 group and 1 arm of the study. All participants will receive the treatment.

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

Approved in United States as Theta Burst Stimulation for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

Erika Forbes

Lead Sponsor

Trials

3

Recruited

180+

Findings from Research

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 randomized, double-blind trial involving 56 patients, intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex showed a significant reduction in negative symptoms for patients with depression, but not for those with schizophrenia.

The treatment was generally safe and well-tolerated, with serious adverse events occurring only in the sham group, indicating that iTBS may be a promising intervention for depressive symptoms in certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. Bodén, R., Bengtsson, J., Thörnblom, E., et al.[2021]

Repeated applications of Theta Burst stimulation (TBS) in rats showed complex effects on neuronal activity markers, with some markers increasing while others decreased, indicating that the response to TBS is not simply accumulative.

Specifically, while the expression of the vesicular glutamate transporter (VGLUT1) increased with stimulation, markers for inhibitory activity like GAD67 and calcium-binding proteins decreased, suggesting a nuanced interaction between excitatory and inhibitory neuronal responses to repeated TBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-dependence of changes in cortical protein expression induced with repeated transcranial magnetic theta-burst stimulation in the rat. Volz, LJ., Benali, A., Mix, A., et al.[2016]

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 study of 50 patients with treatment-resistant depression (TRD), bilateral sequential theta-burst rTMS (bsTBS) demonstrated a 28% remission rate and a 52% response rate, indicating its potential effectiveness for patients who have not responded to other treatments.

The treatment was well tolerated, with only occasional mild adverse events reported, including muscle contractions and headaches, and a very low incidence of serious side effects, suggesting it is a safe option for managing TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral sequential theta burst stimulation for multiple-therapy-resistant depression: A naturalistic observation study. Burhan, AM., Patience, JA., Teselink, JGP., et al.[2022]

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]

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 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 study involving 29 patients with major depression, continuous theta-burst transcranial magnetic stimulation (cTBS) did not show a significant overall improvement compared to sham treatment, indicating modest efficacy.

However, patients who were either medication-free or had unchanged medication status experienced a greater reduction in depression scores with active cTBS, suggesting it may be beneficial for those not responding to traditional pharmacological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary assessment of the therapeutic efficacy of continuous theta-burst magnetic stimulation (cTBS) in major depression: a double-blind sham-controlled study. Chistyakov, AV., Kreinin, B., Marmor, S., et al.[2018]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

2. Netherlands pubmed.ncbi.nlm.nih.gov

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. [2021]

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

Dose-dependence of changes in cortical protein expression induced with repeated transcranial magnetic theta-burst stimulation in the rat. [2016]

4. Ireland pubmed.ncbi.nlm.nih.gov

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

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

Bilateral sequential theta burst stimulation for multiple-therapy-resistant depression: A naturalistic observation study. [2022]

6. 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]

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

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

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

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

9. Netherlands pubmed.ncbi.nlm.nih.gov

Preliminary assessment of the therapeutic efficacy of continuous theta-burst magnetic stimulation (cTBS) in major depression: a double-blind sham-controlled study. [2018]