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An accelerated, high-dose transcranial magnetic stimulation (TMS) therapy significantly improved depression symptoms in a small, open-label study.

Among 21 patients with treatment-resistant depression who underwent the accelerated therapy, depressive symptoms significantly improved by a mean 5 points on the Montgomery-Åsberg Depression Rating Scale (MADRS) after 5 days of treatment, reported Nolan Williams, MD, of the Stanford Brain Stimulation Lab in California, and colleagues.

Overall, 90% of participants achieved a reduction of at least 50% in MADRS scores from baseline, which indicated a treatment response, and this was maintained by 70% of participants at 1-month follow-up, they wrote in the .

Patients reported fatigue and discomfort at the stimulation site and to face muscles, but no serious adverse events or cognitive events were reported, the authors added.

The protocol used in this study -- MRI-guided Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) stimulation -- involves targeting a more precise area in the brain network, increasing the pulse dose, and reducing the time between stimuli, Williams told 乌鸦传媒.

Whereas involves 18,000 pulses across 6 weeks, this method delivered 90,000 pulses across 5 days, researchers reported.

Because of the relatively short treatment period, this therapy would be best used in emergency department and other urgent care settings, Williams explained.

"We think this is a well-positioned intervention for treating folks that are hospitalized," he said. "It seems to be effective, it's durable, and it's quick."

Prior studies have demonstrated that accelerated TMS protocols can be effective among patients with treatment-resistant depression, commented Andrew Leuchter, MD, of the University of California Los Angeles, who was not involved in the study.

However, this study involved even higher frequencies of stimulation and functional connectivity MRI (fcMRI) guidance, which has not been commonly used before, Leuchter added.

"Both of those are potential advances here that could account for the very high rate of remission that they got in this sample," Leuchter told 乌鸦传媒, adding that the unusually high remission rate may also be due to the small sample size and the lack of a control group that could have led to a high sham response rate.

"This is a line of research that should be pursued as depression is a difficult illness to treat," Leuchter said. "At the same time, you have to take it with a grain of salt because we don't have a control comparison here, so we don't know how much of this could be attributable to the treatment part of the study."

While these findings are "encouraging," the rigorous treatment schedule involved in this study may not be practical for many patients with treatment-resistant depression, Leuchter noted.

The study involved patients with major depressive disorder or bipolar II disorder who had failed to respond to at least one other antidepressant medication, and who were currently experiencing a major depressive episode. Those with seizures, cardiac pacemakers, or neurological disorders were excluded.

SAINT stimulation involved a total of 90,000 pulses delivered in 10 sessions per day across 5 consecutive days, at 90% resting motor threshold.

In total, the group was comprised of 12 females and nine males (mean age about 45). Most were on one adjunct antidepressant medication, with mean baseline MADRS scores of 35.

In the intent-to-treat analysis, 19 of 22 (86.4%) of individuals met remission criteria, defined as scores of less than 11 on the MADRS, which was achieved at a mean 2.63 days after treatment initiation (after about 26 10-minute treatments), they noted.

All 21 participants reported suicidality on one of the screening materials at baseline, and all participants reported significantly reduced suicidality measures after SAINT, researchers reported.

Compared with individuals with no prior TMS exposure, those who had previously failed to respond to conventional rTMS treatment (n=6) took more time to respond but experienced similar treatment effects, the authors reported.

Finally, among six patients who relapsed after reaching remission and were retreated a mean 20.5 weeks later, depressive symptoms did not improve even after the second treatment, they noted.

Study limitations included its open-label nature, small sample size, stimulation of a single brain region, fixed stimulation frequencies and intersession intervals, and the lack of state-dependent simulations.

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