Accelerated TMS for Depression

Recruiting in Palo Alto (17 mi)

Overseen by David Spiegel, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Stanford University

Must be taking: Antidepressants

Must not be taking: Ketamine, ECT

Disqualifiers: Pregnancy, Psychotic disorder, Bipolar, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant depression. In a double-blind, randomized, sham-controlled fashion, half the participants will receive accelerated theta-burst stimulation while half will receive sham treatment.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. Participants must be on a stable antidepressant regimen for 6 weeks before joining the study and agree to continue it throughout the study.

What data supports the effectiveness of the treatment Accelerated TMS for Depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS), including theta burst stimulation (TBS), can help treat major depression by targeting specific brain areas. Studies suggest that using TBS as an add-on to standard treatments may improve outcomes, and accelerated TBS might shorten the time needed to see benefits. ^{1 2 3 4 5}

Is accelerated TMS safe for treating depression?

Research indicates that theta-burst transcranial magnetic stimulation (TBS), a form of accelerated TMS, is generally safe and well-tolerated in patients with major depression. Studies show that increasing the stimulation parameters does not lead to more side effects, suggesting a favorable safety profile. ^{4 6 7 8 9}

How is accelerated TMS treatment for depression different from other treatments?

Accelerated TMS (Transcranial Magnetic Stimulation) for depression is unique because it uses a rapid schedule of theta burst stimulation (TBS), which is a patterned form of magnetic pulses, to potentially shorten the time needed to see improvements compared to traditional methods. This treatment targets the dorsolateral prefrontal cortex (DLPFC) and can be used alongside standard medication and therapy, offering a novel approach for those with treatment-resistant depression. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults aged 22-65 with treatment-resistant depression, who haven't tried TMS before. They must be able to understand English, have a stable antidepressant regimen, and not plan on pregnancy. Exclusions include unstable symptoms, certain psychiatric conditions like bipolar disorder or severe personality disorders, substance abuse issues, contraindications to MRI or rTMS (like metal in the head), and recent use of rapid acting antidepressants.

Inclusion Criteria

In good general health, as evidenced by medical history.

For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.

I have access to psychiatric care before and after the study.

Exclusion Criteria

My mood symptoms have not worsened by 30% or more recently.

I've had more than 8 ECT sessions without improvement.

I have a history of serious brain or nerve conditions.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive theta-burst TMS stimulation or sham treatment for 5 days per week

4-8 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

Treatment Details

Interventions

• Active TBS-DLPFC (Transcranial Magnetic Stimulation)
• Sham TBS-DLPFC (Transcranial Magnetic Stimulation)

Trial Overview The study tests an accelerated form of theta-burst stimulation via transcranial magnetic stimulation (TBS-DLPFC) against a sham procedure in people with major depressive disorder. Participants are randomly assigned to either real or fake treatments without knowing which one they're getting.

Participant Groups

Group I: Active TBS-DLPFC Experimental Treatment 1 Intervention

The active group will receive theta-burst TMS stimulation.

Group II: Sham TBS-DLPFC Placebo Group 1 Intervention

The sham group will receive sham theta-burst TMS stimulation.

Active TBS-DLPFC is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Migraines
• Smoking Cessation

🇪🇺 Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

🇨🇦 Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine Stanford, CA

Who Is Running the Clinical Trial?

Stanford University Lead Sponsor

References

1. 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] Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral-prefrontal cortex (DLPFC) exerts antidepressant effects. In this randomised controlled clinical trial we aimed to test the safety and therapeutic efficacy of bilateral theta-burst stimulation (TBS) as an add-on therapy to standard treatment of major depression.

2. Switzerland pubmed.ncbi.nlm.nih.gov

Accelerated rTMS: A Potential Treatment to Alleviate Refractory Depression. [2020] Three decades of clinical research on repetitive transcranial magnetic stimulation (rTMS) has yielded one clear treatment indication in psychiatry for major depression disorder (MDD). Although the clinical response equals the standard treatment algorithms, the effect sizes on the beneficial outcome remain rather modest. Over the last couple of years, to improve the efficacy in resistant depression, two new avenues have been developed: personalization and intensifying rTMS treatment. For the latter, we retrospectively compared accelerated high-frequency rTMS (arTMS) with accelerated intermittent theta burst stimulation (aiTBS) in the refractory depressed state. Although the clinical efficacy was not significantly different between both protocols, our observations substantiate the potential of the accelerated stimulation to shorten the treatment duration from the depressed state to the response state. Any time gain from the depressed state to the recovered state is in the patients' interest.

3. India pubmed.ncbi.nlm.nih.gov

Left intermittent theta burst stimulation combined with right low-frequency rTMS as an additional treatment for major depression: A retrospective study. [2022] Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depression (MD). We retrospectively analyzed the efficacy of intermittent theta burst stimulation (iTBS) on the left dorsolateral prefrontal cortex (DLPFC) combined with low-frequency rTMS (LF-rTMS) on the right DLPFC as an additional therapy to standard medication treatment.

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

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. [2022] Theta burst pattern repetitive transcranial magnetic stimulation (TBS) is increasingly applied to treat depression. TBS's brevity is well-suited to application in accelerated schedules. Sizeable trials of accelerated TBS are lacking; and optimal TBS parameters such as stimulation intensity are not established.

5. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. [2018] Current efforts to improve clinical effectiveness and utility of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depression (MD) include theta burst stimulation (TBS), a patterned form of rTMS. Here, we investigated the efficacy of bilateral TBS to the dorsolateral prefrontal cortex (dlPFC) in patients with MD in additon to ongoing medication and psychotherapy.

6. Germany pubmed.ncbi.nlm.nih.gov

Treatment of major depressive disorder with bilateral theta burst stimulation: study protocol for a randomized, double-blind, placebo-controlled multicenter trial (TBS-D). [2022] Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (dlPFC) is currently evolving as an effective and safe therapeutic tool in the treatment of major depressive disorder (MDD). However, already established rTMS treatment paradigms are rather time-consuming. With theta burst stimulation (TBS), a patterned form of rTMS, treatment time can be substantially reduced. Pilot studies and a randomized controlled trial (RCT) demonstrate non-inferiority of TBS to 10 Hz rTMS and support a wider use in MDD. Still, data from placebo-controlled multicenter RCTs are lacking. In this placebo-controlled multicenter study, 236 patients with MDD will be randomized to either intermittent TBS (iTBS) to the left and continuous TBS (cTBS) to the right dlPFC or bilateral sham stimulation (1:1 ratio). The treatment will be performed with 80% resting motor threshold intensity over six consecutive weeks (30 sessions). The primary outcome is the treatment response rate (Montgomery-Asberg Depression Rating Scale reduction ≥ 50%). The aim of the study is to confirm the superiority of active bilateral TBS compared to placebo treatment. In two satellite studies, we intend to identify possible MRI-based and (epi-)genetic predictors of responsiveness to TBS therapy. Positive results will support the clinical use of bilateral TBS as an advantageous, efficient, and well-tolerated treatment and pave the way for further individualization of MDD therapy.Trial registration: ClinicalTrials.gov (NCT04392947).

7. 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] The aim of this open study was to evaluate the safety and tolerability of theta-burst transcranial magnetic stimulation (TBS) and to assess preliminarily its therapeutic efficacy in patients with major depression. A total of 33 patients were assigned to receive one of four TBS protocols for 10 consecutive work days. TBS consisted of triple-pulse 50-Hz bursts given at a rate of 5 Hz to the left or right dorsolateral prefrontal cortex at different stimulation parameters. Severity of depression was assessed by the Hamilton Depression Rating Scale. Our results indicate that TBS as applied in this study is safe and well tolerated in depressed patients and seems to have antidepressant properties. Increase of stimulation parameters is not associated with more side-effects and adds to its therapeutic effect.

8. 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] Although single- and paired-pulse (sp/pp) transcranial magnetic stimulation (TMS) studies are considered minimal risk in adults and children, the safety profile for theta-burst TMS (TBS) is unknown.

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] Theta-burst transcranial magnetic stimulation (TBS) has been shown to induce potent and long lasting effects on cortical excitability. In a previous open study, we demonstrated safety, tolerability and antidepressant properties of continuous TBS (cTBS) in major depression (MD). The present study was aimed to evaluate the therapeutic efficacy of cTBS in depressed patients using a double-blind, sham-controlled design.