A new alternative for depressed individuals who do not respond or tolerate antidepressant medication appears to be on the horizon.
The noninvasive treatment stimulates the brain with a pulsing electromagnet.
The new study is the first industry-independent, multi-site, randomized, tightly controlled trial of repetitive transcranial magnetic stimulation (rTMS) to discover significant antidepressant effects in a subgroup of patients.
Active rTMS treatment accounted for remissions in 14 percent of antidepressant-resistant patients actively treated, compared to about 5 percent for a simulated treatment.
“Although rTMS treatment has not yet lived up to early hopes that it might replace more invasive therapies, this study suggests that the treatment may be effective in at least some treatment-resistant patients,” said Thomas R. Insel, M.D., director of the National Institute of Mental Health (NIMH), part of the National Institutes of Health, which funded the study.
Researchers from Columbia University, the University of Washington, and Emory University report on their findings in the May 2009 issue of the Archives of General Psychiatry.
“This study should help settle the debate about whether rTMS works for depression,” said Mark George, M.D., of the Medical University of South Carolina, who led the research team.
“We can now follow up clues suggesting ways to improve its effectiveness, and hopefully further develop a potential new class of stimulation treatments for other brain disorders.”
The treatment aims to jumpstart underactive mood-regulating circuitry by targeting the top left front part of the brain with an electromagnetic coil that emits 3,000 pulses over a 37-minute session.
It can be safely administered in a doctor’s office with few side effects – unlike more invasive brain stimulation treatments, such as electroconvulsive therapy (ECT).
Following a decade and a half of studies yielding mixed results, the FDA cleared an rTMS device for treatment of mildly treatment-resistant depression in 2008, based on data submitted by the manufacturer.
The field has been awaiting the results of the NIMH-funded multi-site trial to provide more definitive evidence of efficacy.
Lack of a convincing simulation control treatment that mimics transient tapping and twitching sensations produced by the magnet weakened confidence in findings of some previous rTMS studies.
To address these concerns, the new study sought to blind patients, treaters and raters with a simulation control treatment that produced the same head-tapping sensation and scalp twitching as the active treatment.
A metal insert below the magnet blocked the magnetic field from entering the brain, while electrodes touching the scalp delivered the tapping sensation. This simulation was so convincing that even the treaters could not confidently guess the randomization above chance level, according to the researchers.
A sample of 190 patients who had previously failed to respond to antidepressant medications received at least three weeks of randomized, controlled magnetic stimulations on weekdays for three weeks, with the rTMS magnet aimed at their brain’s left prefrontal cortex. Those who showed improvement received up to an additional three weeks of such blinded treatment.
Thirteen (14 percent) of 92 patients who received the active treatment achieved remission, compared to 5 (about five percent) of 98 patients who received the simulation treatment. Patients who received active rTMS were significantly more likely to reach remission, particularly if they had been moderately, rather than severely, treatment resistant.
The remission rate climbed to nearly 30 percent in an open-label phase of this study in which there was no simulation control. George said this is comparable to rates seen in the STAR*D medication studies.
However, the researchers note that “the overall number of remitters and responders was less than one would like with a treatment that requires daily intervention for three weeks or more, even with a benign side effect profile.”
Patients who responded to active treatment received up to three weeks of additional blinded, controlled rTMS until they achieved remission or stopped showing a meaningful response – so the number of responders did not differ significantly from the number of remitters.
These patients who remitted then received a combination of medications intended to help maintain the treatment effect. Despite failing to respond to medications in the past, most remained in remission for several months.
Study participants who failed to improve during the blinded phase entered a course of open-label rTMS. Among those who had been in the active rTMS group, 30 percent achieved remission during this second phase.
This suggests that some patients might require as many as 5-6 weeks of daily rTMS treatment, according to George. Most patients who remitted required 3-5 weeks of treatment.