New trial evaluates rTMS for adolescent depression

The need for new therapies for adolescent depression is critical. As many as 40 percent of young people with major depressive disorder fail to respond to pharmacotherapy and psychotherapy, leading to an increased risk of psychiatric hospitalization, poor psychosocial development, and attempted or completed suicide. For these patients, repetitive transcranial magnetic stimulation (rTMS) may be a safe, well-tolerated and effective therapeutic option.

A noninvasive modality, rTMS uses brief magnetic pulses to depolarize neurons in the brain. The magnetic field penetrates the skull, producing electrical currents in cortical tissue. Most studies have used high-frequency rTMS to enhance excitability in the left dorsolateral prefrontal cortex (DLPFC), although some research has focused on the use of low-frequency stimulation to normalize overactivity in the right DLPFC.

Treatment is usually administered five times a week for a total of 30 sessions (3,000 pulses per session at 120 percent motor threshold) over a four- to six-week period. The procedure is approved for use in adults with major depressive disorder, and evidence supports its safety and efficacy in this population. But little is known about rTMS in children.

According to Paul E. Croarkin, D.O., a psychiatrist at Mayo Clinic's campus in Rochester, Minnesota, "A number of studies have shown that rTMS is not associated with adverse neuropyschological events in adults, and some studies have indicated time-limited improvements in attention, memory and learning after treatment. But we are not sure whether this is true for young patients."

So Dr. Croarkin and colleagues conducted two prospective, open pilot trials of active rTMS using treatment sites and dosing parameters based on guidelines established in adult studies. The results appeared in the December 2013 issue of Frontiers in Psychiatry.

"Most of the 14 children who completed the trials had some benefit for their depression, which is encouraging," Dr. Croarkin says. "It's also reassuring to note that none of the patients or family members reported any changes in memory, cognitive function or attention. In fact, there was a modest improvement in these areas. These findings reflect what we have seen in clinical practice. Still, you must be careful and skeptical with an open-label trial. It may be there are benefits to just having kids coming in every day for four to six weeks."

The next step is a large, randomized, double-blind, sham-controlled study, currently recruiting patients at Mayo Clinic.

"This approach will allow us to validate rTMS treatment outcomes in a scientifically rigorous manner using all the protocols and parameters developed in definitive adult studies," Dr. Croarkin explains. "Many of the patients enrolled in our trials have not done well on multiple medications. If we see positive results in this trial, we may be able to offer rTMS to depressed patients who don't want to take medicine or don't respond to it. We're also hoping we can expand the use of neurostimulation to other disorders, including bipolar disorder and autism."

In addition to evaluating the antidepressant effects of rTMS, the sham-controlled study will use proton magnetic resonance spectroscopy to map the distribution of brain metabolites and determine whether certain neurochemical resonances are associated with remission or improvement of clinical depressive symptoms after rTMS therapy.

"We're trying to understand not only if this works, but the mechanisms as well. For child psychiatry to evolve, we need to understand what happens in brains that are stressed by depression and how they respond to various treatments," Dr. Croarkin says.

For more information

Wall CA, et al. Neurocognitive effects of repetitive transcranial magnetic stimulation in adolescents with major depressive disorder. Frontiers in Psychiatry. 2013;4:165.

A Randomized, Double-Blinded, Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation in Depressed Adolescents. Clinical Trials at Mayo Clinic.