Deep TMS for Depression

(NACC-D Trial)

Overseen By Amanda Chao, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Rotman Research Institute at Baycrest

Must not be taking: Benzodiazepines, Hypnotics, others

Disqualifiers: Psychotic disorder, Bipolar, Epilepsy, others

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

Compensation: Varies

Number of Visits: 6

Duration: 1 week

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if an accelerated version of deep Transcranial Magnetic Stimulation (dTMS), a non-invasive brain treatment, can reduce symptoms of depression in older adults. It targets individuals aged 60 to 85 with Major Depressive Disorder who have not responded well to antidepressants. Participants will receive either the actual dTMS treatment or a placebo version that mimics the sensation without affecting the brain. Ideal candidates have experienced depression for more than four weeks but less than five years and have not found relief with previous treatments. As an unphased trial, this study provides a unique opportunity for participants to contribute to innovative research that could lead to new treatment options for depression.

Will I have to stop taking my current medications?

If you are stable on your current medications for at least 2 months and do not expect to change them during the study, you can continue taking them. However, if you are on unstable doses of certain medications or require daily doses of benzodiazepines or hypnotics, you may need to adjust your medication use.

What prior data suggests that this accelerated dTMS protocol is safe for older adults with Major Depressive Disorder?

Research has shown that deep Transcranial Magnetic Stimulation (dTMS) is generally safe and well-tolerated. In studies focused on depression in older adults, dTMS has demonstrated high rates of improvement and recovery, indicating good safety results. For instance, one study found that a faster version of dTMS led to an 80% improvement rate, with 51% of participants fully recovering. Another study showed that just 20 sessions of dTMS resulted in a 74% improvement rate and a 58% recovery rate.

These findings suggest that dTMS is not only effective but also safe for treating depression, even in older adults. While some side effects may occur, the treatment is usually well-tolerated, making it a promising option for those who haven't found success with traditional antidepressants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for depression, like antidepressant medications or psychotherapy, often take weeks to show effectiveness and can have various side effects. Deep Transcranial Magnetic Stimulation (dTMS) is unique because it uses magnetic fields to stimulate nerve cells in the brain non-invasively. Its delivery method—intermittent theta burst stimulation (iTBS)—is designed to potentially provide faster results with fewer side effects compared to traditional therapies. Researchers are excited about this approach because it offers a novel way to target specific brain areas associated with depression, possibly leading to quicker and more effective relief for patients.

What evidence suggests that deep TMS might be an effective treatment for depression?

Research has shown that deep Transcranial Magnetic Stimulation (dTMS) can help reduce symptoms of depression. One study found that 38.4% of participants responded positively to dTMS, compared to 21.4% who received a sham treatment, indicating that dTMS works better than a placebo. This trial will compare the effects of active dTMS sessions with sham stimulation sessions. A review of several studies confirmed that dTMS is a promising treatment, especially when combined with antidepressants. Additionally, another study reported that 14.1% of participants experienced complete relief from symptoms. These findings suggest that dTMS may benefit those with depression, particularly if other treatments haven't been effective. ^{1 5 6 7 8}

Who Is on the Research Team?

Linda Mah, MD

Principal Investigator

Baycrest Rotman Research Institute

Are You a Good Fit for This Trial?

This trial is for older adults aged 60-85 with Major Depressive Disorder who haven't had success with antidepressants. Participants should be able to attend sessions over 5 consecutive days and have no other conditions that could interfere with the treatment or skew its results.

Inclusion Criteria

Participants are willing to provide informed consent

Participants are able to follow the treatment schedule

Participants have a satisfactory safety screening questionnaire for TMS

Exclusion Criteria

Participants have a personal history of epilepsy

Participants have a metal plate in their head (such as an ear implant, implanted brain stimulators, aneurysm clips). Dental devices and implants that are non-magnetic are safe

Participants have a cardiac pacemaker

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive accelerated deep Transcranial Magnetic Stimulation (dTMS) sessions over 5 consecutive days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Deep Transcranial Magnetic Stimulation

Trial Overview The study tests an accelerated deep Transcranial Magnetic Stimulation (dTMS) protocol, comparing a real Active Brainsway H7-Coil dTMS System against a sham version to see if it can quickly reduce depression symptoms safely.

How Is the Trial Designed?

Group I: 20-40 sessions of iTBS dTMS Experimental Treatment 1 Intervention

Participants will receive dTMS if randomized into the active condition. The motor threshold (MT) will be measured by delivering single stimulations to the motor cortex with gradually increased intensity. The stimulation protocol consists of 6-8 dTMS sessions of intermittent theta burst stimulation delivered at an intensity of 80-90% of resting MT each day for five consecutive days

Group II: 20-40 sessions of sham stimulation Placebo Group 1 Intervention

Participants will receive sham intervention if randomized into sham condition. The sham intervention consists of treatment with similar technical parameters which induce scalp sensations but do not penetrate into the brain.

Who Is Running the Clinical Trial?

Rotman Research Institute at Baycrest

Lead Sponsor

Trials

11

Recruited

460+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4329899/

Efficacy and safety of deep transcranial magnetic ... In a duration-adaptive study (3-week acute treatment phase with a 3-week extension for clinical improvers), George et al (19) reported remission rates of 14.1% ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S002239562400270X

Clinical efficacy of deep transcranial magnetic stimulation ... We systematically reviewed 28 clinical trials comparing active dTMS to a sham/controlled condition to characterize dTMS efficacy across diverse psychiatric and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10257110/

Clinical Efficacy of Deep Transcranial Magnetic Stimulation ... The authors highlight dTMS as an effective intervention, especially when administered in conjunction with antidepressants. However, systematic ...

4. cognitivefxusa.com cognitivefxusa.com/blog/tms-success-rates-for-depression

TMS Success Rates for Depression: Compare TMS Types Around 50% of individuals who recover from depression following rTMS interventions experience a relapse within 12 months. Deep Transcranial ...

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1473743/full

The effect of repetitive and Deep Transcranial Magnetic ... Regarding dTMS, a multicenter randomized sham-controlled trial revealed response rates of 38.4% for dTMS versus 21.4% for sham conditions in ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S016517812500215X

Safety and efficacy of Deep TMS for adolescent depression ... Anxiety symptoms also improved in the majority of patients, with 66 % of patients reaching response and 40.2 % achieving remission on GAD-7 after 36 Deep TMS ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10856385/

Safety and Efficacy of Deep TMS for Late-Life Depression These high response and remission rates in patients with treatment-resistant late-life depression suggest that Deep TMS is a safe, well- ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0165178123004328

Real world efficacy and safety of various accelerated deep ... Highlights · Accelerated Deep TMS with the H1 coil has an 80% response and 51% remission rate. · The six-month durability of accelerated Deep TMS is 93%.