High-Dose iTBS for Depression

No longer recruiting at 2 trial locations

Overseen By Elizabeth Clancy

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Anticonvulsants, others

Disqualifiers: Substance abuse, Bipolar, Schizophrenia, OCD, others

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

Compensation: Varies

Number of Visits: 81

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat depression using intermittent theta burst stimulation (iTBS). It compares an active version of the treatment to a placebo to determine its effectiveness in reducing depression symptoms. The treatment consists of several sessions over five days, assessing its impact both shortly after and weeks after treatment. Individuals who have not found relief from regular antidepressants may be suitable candidates. As an unphased trial, this study provides a unique opportunity to investigate innovative treatments for depression.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but you must not have started or increased any psychotropic medications in the 4 weeks before screening. Also, you cannot take more than 2 mg of lorazepam daily or any anticonvulsants.

What prior data suggests that this iTBS treatment is safe for depression?

Research has shown that intermittent theta burst stimulation (iTBS) for depression is generally safe. Most patients tolerate iTBS well. Studies found that side effects were usually mild and short-lived. Some people experienced headaches or scalp discomfort, but these effects typically subsided soon after treatment. Importantly, the risk of serious side effects was low. This makes iTBS a promising treatment for depression, offering a good balance of benefits and safety for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about high-dose intermittent theta-burst stimulation (iTBS) for depression because it offers a rapid and potentially more effective alternative to traditional treatments like antidepressants and standard repetitive transcranial magnetic stimulation (rTMS). Unlike standard rTMS, which typically requires daily sessions over several weeks, high-dose iTBS delivers multiple short bursts of magnetic pulses in just a few days, potentially accelerating the onset of therapeutic effects. Additionally, by targeting the brain's motor threshold at a higher intensity, iTBS may enhance the treatment's efficacy in alleviating depressive symptoms, providing hope for those who haven't responded well to existing therapies.

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

In this trial, participants will receive either Active iTBS or Sham iTBS. A previous study found that 79% of people who received accelerated intermittent theta burst stimulation (iTBS) for depression experienced significant symptom improvement, reaching remission. Other research suggests that just two days of active iTBS can quickly and safely reduce depressive symptoms. iTBS sends short bursts of energy to the brain and appears more effective than some traditional methods. Overall, current evidence shows that iTBS is as safe and effective as other similar treatments for depression. ^{3 4 6 7 8}

Who Is on the Research Team?

Daniel Blumberger, MD

Principal Investigator

CAMH

Are You a Good Fit for This Trial?

This trial is for outpatients aged 18-65 with major depressive disorder, who haven't responded well to antidepressants or can't tolerate them. Participants must have a certain depression score, be able to follow the treatment schedule, and not be on new psychotropic meds for the last 4 weeks. Exclusions include unstable medical conditions, metal implants near the head, pregnancy, certain psychiatric diagnoses like bipolar or schizophrenia, substance abuse within 3 months, high risk of suicide or taking specific medications.

Inclusion Criteria

I haven't started or increased any mental health medication in the last 4 weeks.

have a score > 18 on the HRSD-17 item

able to adhere to the treatment schedule

Exclusion Criteria

I have had ECT treatment before that did not work for me.

have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed

I do not have major brain or nerve conditions like severe head injury, Parkinson's, or multiple sclerosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active or sham iTBS administered 8 times daily for 5 days

1 week

40 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Assessments at 1-week and 4-weeks post-treatment

Open-label extension

Participants not meeting response criteria at 4-week follow-up are offered a second course of active rTMS treatment

1 week

40 sessions (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Active iTBS
• Sham iTBS

Trial Overview The study tests an accelerated schedule of active intermittent theta burst stimulation (iTBS) against a placebo control over five days. iTBS is a type of repetitive transcranial magnetic stimulation (rTMS), which uses magnetic fields to stimulate nerve cells in the brain. Depression severity will be measured at multiple points before and after treatment.

How Is the Trial Designed?

Group I: Active iTBS Experimental Treatment 1 Intervention

Administered 8 times daily at approximately 50 minutes intervals (between session end and start) for 5 days. Each session will deliver 1800 pulses of active iTBS (bursts of 3 pulses at 50 Hz, bursts repeated at 5 Hz, with a duty cycle of 2 seconds on, 8 seconds off, over 60 cycles / \~10 minutes) at a target intensity of 110% of the subject's resting motor threshold.

Group II: Sham iTBS Placebo Group 1 Intervention

Administered 8 times daily at approximately 50 minutes intervals (between session end and start) for 5 days, using a sham coil that reproduces auditory and tactile sensations of stimulation and has an identical external appearance. Each session will deliver 1800 pulses of sham iTBS (bursts of 3 pulses at 50 Hz, bursts repeated at 5 Hz, with a duty cycle of 2 seconds on, 8 seconds off, over 60 cycles / \~10 minutes) at a target intensity of 110% of the subject's resting motor threshold.

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Citations

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

Accelerated Intermittent Theta-Burst Stimulation and ... Ten sessions per day for 5 days achieved 79% remission in a sham-controlled randomized clinical trial—substantially better than remission rates ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725000023

Efficacy study of intermittent theta burst stimulation(iTBS) in ... The current study suggests that two days of active iTBS to the DLPFC region can rapidly, safely, and effectively improve depressive symptoms in adolescents ...

3. nature.com nature.com/articles/s41380-024-02630-5

Theta burst stimulation for depression: a systematic review ... Theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39212556/

Efficacy and Safety of Intermittent Theta Burst Stimulation ... iTBS and HF-rTMS have comparable efficacy and safety profiles in treating MDD based on current evidence. Both neuromodulation techniques are superior to sham ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07033780

NCT07033780 | Theta-Burst Stimulation to Treat Depression The goal of this clinical trial is to explore the effects of non-invasive brain stimulation protocols using intermittent theta-burst stimulation (iTBS) on ...

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

Theta burst stimulation for depression: a systematic review ... Our results suggest that iTBS (L-DLPFC) had a favorable risk-benefit balance for the treatment of depression because iTBS (L-DLPFC) had a high ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006322325013563

Efficacy and Safety of Accelerated Intermittent Theta-burst ... Developing safe and rapid treatments is crucial for adolescent major depressive disorder (MDD). While 10-session daily accelerated ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0165032723002604

Outcome of transcranial magnetic intermittent theta-burst ... iTBS is the most utilized rTMS protocol for depression in Sweden. Real-life response rates of iTBS are similar to clinical trials.