major depression

Daniel Blumberger, MD, MSc, on a New, 3-Minute Option for Treatment-Resistant MDD

Repetitive transcranial magnetic stimulation (rTMS) was first approved by the US Food and Drug Administration (FDA) in 2008 to treat patients with major depressive disorder (MDD) whose depression has not responded adequately to standard therapies.

Much more recently, the FDA cleared a significantly shortened version of rTMS for treatment-resistant MDD.

The newer, shorter version—called intermittent theta burst stimulation (iTBS) —lasts only 3 minutes per session compared with the 20 to 40 minutes required for each rTMS session, thus increasing the efficiency and expediency of the treatment.

The evidence supporting iTBS’s effectiveness arose from the THREE-D study (N = 414), conducted by Daniel Blumberger, MD, MSc, FRCPC, and colleagues.1 In THREE-D, approximately 33% of patients treated with iTBS protocol achieved response/remission, and 50% experienced an improvement in their depressive symptoms.2

Perhaps most importantly, treatment with iTBS was found to be noninferior to the standard, longer rTMS protocol, noted Dr Blumberger, who is the medical head and co-director of the Temerty Centre for Therapeutic Brain Intervention at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada.

Consultant360 spoke with Dr Blumberger about the ins and outs of iTBS therapy—how it works, where patients can access it, and its clinical implications for treatment-resistant MDD.

Consultant360: What does iTBS add to the landscape of available options for treatment-resistant MDD? What makes this technology unique? 

Daniel Blumberger: This new treatment adds a tremendous opportunity to increase the capacity of clinics that provide rTMS. It may allow clinics to greatly increase the numbers of patients treated because a treatment session can be delivered in 3 minutes compared with 20 to 40 minutes for standard forms of rTMS. iTBS delivers magnetic field pulses in a pattern that is similar to one of the brain’s natural rhythms. As a result, we believe that it is a far more efficient form of stimulation, requiring less time and fewer number of pulses per session for a similar therapeutic outcome. 

C360: Why might iTBS be beneficial for treatment-resistant depression when other treatments have failed?

DB: TMS is a non-invasive way of directly stimulating the brain circuitry that is impaired among people who develop depression. For a significant proportion of patients, medication and talk therapy do not effectively alleviate depression. This treatment works through a very different mechanism of action than medications and talk therapy, so there is hope for people who have not had response to these other treatments.

C360: Are all patients with treatment-resistant MDD potential candidates for this treatment, or are there any patient populations for whom iTBS and/or rTMS is contraindicated? 

DB: Most patients with MDD are candidates for this treatment. However, some medications, such as benzodiazepines and anticonvulsants, may interfere with the intended effects of the treatment. It is important that patients treated with these medications are assessed by an expert before starting treatment.

C360: How does iTBS work? What is a typical session like, compared with an rTMS session, and how often do sessions take place?

DB: We do not know the exact mechanism of action, but we believe that the treatment modulates the brain circuitry involved in depression through stimulating one structure in the circuit called the dorsolateral prefrontal cortex. Since the brain is so highly interconnected, stimulation at this site can modulate other parts of the brain involved in the pathophysiology of depression.

During a 3-minute iTBS session, a magnetic coil is placed over the dorsolateral prefrontal cortex and magnetic field pulses are delivered to the brain. A typical treatment course occurs 5 days a week over the course of 4 to 6 weeks.

C360: Is iTBS well-tolerated? Are there any side effects associated with this treatment?

DB: The treatment is generally well-tolerated, but most people have some skin irritation and discomfort over the site of stimulation and about half of people will have a transient headache at some point during the course of treatment. 

C360: Is the treatment affordable and easily accessible?

DB: The cost of the treatment varies widely by region. There are many clinics operating around the world, but they are usually near urban centers. It is possible that iTBS may increase the accessibility of the treatment because many more people could receive the treatment per machine.

C360: How might iTBS fit into a depression treatment regimen? Is iTBS intended to be used alone or alongside other forms of treatment, such as psychotherapy?

DB: In our study, most patients were receiving stable doses of medications during the course of treatment. It can be difficult for some patients to taper off of medications, and there may be some benefits that patients are deriving from the medication that we do not want to take away by stopping those medications.

Since rTMS requires a significant time and travel investment on the part of the patient, it is generally considered as a treatment option for patients who have not responded to adequate medication treatment or an evidence-based talk therapy.

Daniel Blumberger, MD, MSc, FRCPC, is the Medical Head and Co-Director of the Temerty Centre for Therapeutic Brain Intervention, Head of the Late-Life Mood Disorders Clinic, and a Clinician Scientist for the Campbell Family Research Institute at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada. He is also an associate professor in the Department of Psychiatry at the University of Toronto.

—Christina Vogt


1. Blumberger DM, Vila-Rodriguez F, Thorpe KE, et al. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018;391(10131):1683-1692.

2. MagVenture, Inc: FDA clears 3-minute, non-pharmaceutical depression treatment [press release]. Atlanta, GA. MagVenture, Inc. August 22, 2018. Accessed on September 6, 2018.