Repetitive TMS provides a safe, effective alternative for some adolescents with major depressive disorder

Dr. Wall and adolescent patient discuss rTMS treatment

Enlarge

A study conducted at Mayo Clinic suggests that repetitive transcranial magnetic stimulation (rTMS) is a safe, feasible and potentially effective therapy for adolescents with treatment-resistant major depressive disorder (MDD).

A team from the Department of Psychiatry and Psychology at Mayo Clinic in Rochester, Minn., led by Christopher A. Wall, M.D., recently received approval from the Food and Drug Administration (FDA) and three grants to study the adjunctive use of rTMS in adolescents. "We believe our previous study is the first rigorously standardized U.S. trial of rTMS for depressed adolescents," says Dr. Wall. "Previous studies have been conducted in Australia and Israel, but the dosing used in those trials was variable and less than adult dosing levels. We felt it was important to use adult treatment parameters to give kids the best chance for treatment benefit."

Children and parents report improvement

Recently, an initial multicenter trial led by Mayo Clinic (including Rush University and the University of Texas Southwestern Medical Center) was conducted with eight adolescents who had MDD that had not responded sufficiently to two adequate antidepressant medication trials. Participants were treated with a stable dose of a selective serotonin reuptake inhibitor during the trial, and they received 30 daily rTMS treatments given five days a week over six to eight weeks. Dosage was 3,000 stimulations in each treatment session at 120 percent of the motor threshold.

All participants continued to receive their medications during the treatment period and all participants received the treatment. "This was an open trial, so no placebos were used," notes Dr. Wall. "All of the kids and their parents knew they were receiving the active treatment."

The possibility of provoking seizures in adolescent patients was a consideration, but no adverse events occurred. Initial outcomes indicate that the treatment is safe and well tolerated. The adolescent participants also seemed to respond more briskly to treatment than did the adults who participated in previous trials.

Of the eight trial participants, seven completed the full course of treatment and five of the seven reported improvement initially and at the six-month follow-up visit. "The seven participants who received all 30 treatments have said they would do it again and so did their parents," says Dr. Wall. "Interestingly, the treatment effects lasted when measured six months after the final session."

2011 trial uses MRS

Dr. Wall and Mayo Clinic received a second investigational device exemption from the FDA in July 2011. The new trial for use of rTMS for adolescents with MDD, started in September, uses the same treatment parameters and treats at the same location as the initial trial.

In the new study, however, researchers will use magnetic resonance spectroscopy (MRS) to look at participants' brains before treatment, at the end of treatment and again six months after the final treatment. MRS will be used to look for changes in chemical signals instead of looking at the structure of the left dorsolateral prefrontal cortex and anterior cingulate cortex. Both areas have been associated with depression and treatment response.

Dr. Wall's paper about the initial trial, "Adjunctive Use of Repetitive Transcranial Magnetic Stimulation in Depressed Adolescents: A Prospective, Open Pilot Study," appears in the September 2011 issue of the Journal of Clinical Psychiatry (2011;72[9]:1263-9).

FDA exemptions support clinical trials

A significant number of adolescents who have major depressive disorder (MDD) do not benefit from currently available medications, psychotherapy or social support treatments. Considered separately, these treatment approaches fail to provide adequate clinical improvement in approximately 40 percent of adolescents with MDD and produce complete remission in only 30 percent of adolescent patients.

In 2008, the Food and Drug Administration (FDA) approved the use of transcranial magnetic stimulation (rTMS) for some adults with MDD. The use of rTMS for adolescents, however, has not been adequately studied.

Points to remember

• Previous trials of repetitive transcranial magnetic stimulation (rTMS) in depressed adolescents used less robust treatment parameters than the initial multicenter rTMS study led by Mayo Clinic.
• TMS treatment dosing consistent with adult protocols was found to be safe, feasible and effective in this group of adolescents.
• Treatment benefits of rTMS in adolescents appeared durable at the six-month follow-up visit.