Repetitive transcranial magnetic stimulation of the brain has been shown to reduce the effects of treatment-resistant depression, but study results show that intermittent theta-burst stimulation may be more efficient and effective.
Repetitive transcranial magnetic stimulation (rTMS) of the brain has been shown to reduce the effects of treatment-resistant depression. The treatment, which involves external electrodes that use a magnetic pulse to stimulate specific areas of the brain, with few adverse effects, typically lasts 40 minutes. It was approved by the FDA over 20 years ago.
However, study results from 2018 and more recently demonstrate that intermittent theta-burst stimulation (iTBS) may be more efficient and effective. Published online yesterday in the American Journal of Psychiatry, researchers from Stanford University’s School of Medicine show their promising interim findings on Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), from the Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression trial, a form of iTBS. Ninety percent of their study subjects demonstrated a rapid remission of their depressive symptoms.
According to the press release announcing the Stanford investigators’ findings, there are 3 major reasons iTBS is superior compared with rTMS:
Their findings also focus on 2 particular areas of the brain, comprising 1 circuit: the left dorsolateral prefrontal cortex and the subgenual anterior cingulate cortex. This connection in this circuit is weaker in patients diagnosed as depressed. The primary outcome was change in the Montgomery-Asberg Depression Rating Scale (MADRS) from baseline to right after SAINT.
The study population originally consisted of 23 participants. Their ages ranged from 19 to 78 years, with a mean (SD) age of 44.86 (17.21) years; more than half (13) were female. The 2 participants who ended up not completing the study were excluded for “having a very high motor threshold (>90% machine output)” and a history of extreme anxiety to several prior therapies (eg, intravenous ketamine infusions).
The 21 participants who completed the trial had to have diagnosed major depressive disorder (n = 19) or bipolar II disorder (n = 2), per Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, and had to be currently be experiencing a nonpsychotic major depressive episode. All were from the Depression Research Clinic at Stanford and reported previous suicidal thoughts. Before iTBS began, 2 magnetic resonance imaging (MRI) scans were performed on the participants’ brains: structural and resting-state functional.
Treatment with iTBS consisted of 10 consecutive 10-minute treatments, each with a 50-minute break afterward, for 5 days. Pulses totaled 18,000 each day and 90,000 overall. With adverse effects that only included fatigue and mild discomfort, the results are impressive. Cognitive inhibition improved in both the Delis Kaplan Executive Function System color-word inhibition task (t = 4.92; df = 16; P <.001; d = 1.19) and color-word inhibition switching task (t = 3.77; df = 16; P = .002; d = 0.91).
The mean (SD) time to response was 2.3 (1.13) days, while the mean (SD) time to be considered to have achieved depression remission was 2.63 (1.21) days. In addition, there was a 90.48% improvement post SAINT in the MADRS score, and everyone who responded to the treatment was considered to be in remission from their depression. This latter percentage remained high, at 86.4% of participants, following an intent-to-treat analysis. Plus, in the month after SAINT, “70% of participants continued to meet response criteria,” the authors noted, and between 80% and 100% did not regress in their suicidal thoughts.
“There’s never been a therapy for treatment-resistant depression that's broken 55% remission rates in open-label testing,” stated Nolan Williams, MD, assistant professor of psychiatry and behavioral sciences and a senior author of the study. “Electroconvulsive therapy is thought to be the gold standard, but it has only an average 48% remission rate in treatment-resistant depression. No one expected these kinds of results.”
To strengthen research in this area and confirm the remission rates they saw, the investigators recommend additional studies on individualized functional connectivity MRI—guided targeting methods, as well as clinical studies that compare remission rates of iTBS and rTMS, both when a treatment is individualized and when it is not.
Cole EJ, Stimpson KH, Bentzley BS, et al. Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression [published online April 6, 2020]. Am J Psychiatry. doi: 10.1176/appi.ajp.2019.19070720.