Theta-Burst Stimulation for Depression

(INSPiRE-D Trial)

Overseen By Dewi Clark, MHSc

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Centre for Addiction and Mental Health

Must be taking: Antidepressants

Must not be taking: Antipsychotics, Antiepileptics, Benzodiazepines

Disqualifiers: Bipolar, Psychotic disorder, Seizures, others

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

Compensation: Varies

Number of Visits: 8

84 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for depression using theta-burst stimulation (TBS), which applies magnetic pulses to the scalp to alter brain activity. Researchers aim to determine if two types of TBS, compressed and spaced, can enhance the brain's ability to reorganize itself and alleviate depression symptoms. Individuals with Major Depressive Disorder who have maintained a stable antidepressant regimen for at least four weeks and do not have other major mental health conditions may qualify for this trial. Participants will receive both types of TBS, helping researchers identify which method is more effective. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

If you are currently taking antidepressants, you must be on a stable regimen for at least 4 weeks before joining the trial. However, you cannot participate if you are taking antipsychotics, antiepileptics, or benzodiazepines, unless it's gabapentin or pregabalin for chronic pain with a stable dose for 4 weeks.

What prior data suggests that this theta-burst stimulation protocol is safe for treating depression?

Research has shown that both compressed and spaced intermittent theta-burst stimulation (iTBS) are generally safe for people. iTBS uses magnetic pulses to influence brain activity and has been well-tolerated by individuals with depression, with no serious side effects reported. A large study found that iTBS is as safe as another approved treatment, 10Hz rTMS, and it is FDA-approved for treating depression, indicating its safety for medical use.

Some studies have specifically examined compressed iTBS. One study found it safe for individuals with treatment-resistant depression, although satisfaction and comfort were slightly lower compared to other methods. For spaced iTBS, research suggests it is also safe and well-tolerated, even when used twice a day.

While this trial is in its early phase, meaning safety is still being closely monitored, the available evidence suggests both treatments are generally safe and well-tolerated in people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Theta-Burst Stimulation (TBS) for depression because it offers a new way to engage the brain using rapid pulses of magnetic energy, which is different from traditional treatments like antidepressants and psychotherapy. Unlike these standard options that might take weeks to show results, TBS has the potential to produce faster improvements in mood. Additionally, this method could provide an alternative for patients who don't respond well to existing therapies, as it targets brain activity more directly and non-invasively.

What evidence suggests that this trial's treatments could be effective for depression?

Research shows that theta-burst stimulation, a non-invasive brain treatment, can help reduce depression symptoms. In this trial, participants will receive either Compressed iTBS or Spaced iTBS. Compressed iTBS has improved these symptoms, with some studies noting relief as quickly as within one week. It is often used for individuals whose depression hasn't improved with other treatments. Meanwhile, Spaced iTBS also appears promising, with evidence suggesting it could enhance the effects of antidepressants when sessions are spread out. Both methods aim to improve brain plasticity, the brain's ability to adapt and change, potentially leading to a better mood and reduced depression symptoms. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals aged 18 to 50 with Major Depressive Disorder. Participants must be able to undergo brain scans and tolerate non-invasive brain stimulation. People are excluded if they have conditions that conflict with magnetic or electrical therapies, or if they can't complete the study visits.

Inclusion Criteria

Hamilton Rating Scale for Depression (HRSD-17) score > 7

I have been on the same antidepressant for at least 4 weeks.

Right handed or ambidextrous, assessed using the Edinburgh Handedness Inventory (EHI)

Exclusion Criteria

I am not on any antipsychotic, antiepileptic, or benzodiazepine medications, except for stable doses of gabapentin or pregabalin for chronic pain.

I am either 17 years old or younger, or older than 51.

Presence of any DSM-5 diagnosis (other than MDD), known to be associated with prefrontal cortical dysfunction, including lifetime diagnoses of bipolar disorder, intellectual disability, or a psychotic disorder, assessed using the SCID-5 and as per investigator judgement

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Initial Assessment and Randomization

Participants undergo MRI brain scan and are randomized to iTBS-s or iTBS-c protocol

1 visit

1 visit (in-person)

First Treatment Phase

Participants receive 3 sessions of either iTBS-s or iTBS-c intervention, including TMS-EEG measurements and post-iTBS questionnaires

3 visits over 1-2 weeks

3 visits (in-person)

Washout Period

Participants undergo a washout period of at least 2 weeks before switching to the opposite iTBS intervention

2 weeks

Second Treatment Phase

Participants receive 3 sessions of the opposite iTBS intervention, including TMS-EEG measurements and post-iTBS questionnaires

3 visits over 1-2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Theta-Burst Stimulation

Trial Overview The trial tests two types of intermittent theta-burst stimulation (iTBS) protocols on depression: compressed iTBS (iTBS-c) and spaced iTBS (iTBS-s). It aims to see which protocol better improves brain plasticity and reduces depression symptoms by alternating treatments after a washout period.

How Is the Trial Designed?

Group I: Spaced iTBS Experimental Treatment 1 Intervention

Upon completion of Visits 1-2 (Screening and MRI), participants randomized to iTBS-s will complete a baseline TMS-EEG measurement, one iTBS-s intervention session, and post-iTBS TMS-EEG measurements in each of Visits 3-5. Following this, participants will undergo a washout period of at least two weeks. Then, participants will return to complete the opposite iTBS intervention across Visits 6-8. The procedures and visits will be identical, but the participant will receive the other iTBS intervention that they were not initially randomized to.

Group II: Compressed iTBS Active Control 1 Intervention

Upon completion of Visits 1-2 (Screening and MRI), participants randomized to iTBS-c will complete a baseline TMS-EEG measurement, one iTBS-c intervention session, and post-iTBS TMS-EEG measurements in each of Visits 3-5. Following this, participants will undergo a washout period of at least two weeks. Then, participants will return to complete the opposite iTBS intervention across Visits 6-8. The procedures and visits will be identical, but the participant will receive the other iTBS intervention that they were not initially randomized to.

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Brain Canada

Collaborator

Trials

22

Recruited

6,100+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07033780

NCT07033780 | Theta-Burst Stimulation to Treat Depression This trial will compare the effects of the compressed iTBS (iTBS-c) protocol, which is commonly used to treat depression, and the spaced iTBS ( ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11609094/

Theta burst stimulation for depression: a systematic review ... The current study outcomes included the response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0166432824005175

Four weeks standard vs. one week accelerated intermittent ... aiTBS with 1200 pulses and five daily sessions lead to amelioration of symptoms within one week. But benefit, satisfaction, tolerability was slightly lower.

4. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT04684706

Compressed Intermittent Theta Burst Stimulation Approximately 30% of MDD patients suffer treatment resistant depression (TRD), with at least 2 failed adequate trials of pharmacotherapy. Repetitive ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11238064/

Accelerated Intermittent Theta-Burst Stimulation and ... This randomized clinical trial assesses the effectiveness of accelerated intermittent theta-burst stimulation for depressive symptom reduction

6. nature.com nature.com/articles/s41380-025-03183-x

Intermittent theta burst stimulation for non-suicidal self ... Stimulating the LDLPFC with iTBS for 4–6 weeks has shown comparable efficacy for treatment-resistant depression (TRD). Compared with high- ...