rTMS No Better Than Sham Stimulation for Severe Depression

Megan Brooks

July 05, 2018

Repetitive transcranial magnetic stimulation (rTMS) is no better than sham rTMS for treatment-resistant depression (TRD), results of a large randomized trial show.

However, 40% of patients achieved remission regardless of whether they received active or sham rTMS, although for those with comorbid posttraumatic stress disorder (PTSD), rates of remission rates were lower in both treatment groups.

"This finding may reflect the importance of close clinical surveillance, rigorous monitoring of concomitant medication, and regular interaction with clinic staff in bringing about significant improvement in this treatment-resistant population," the investigators write.

The study was published online June 27 in JAMA Psychiatry.

First Large-Scale Trial

In veterans, TRD is a "major clinical challenge," given the high risk for suicidal thoughts and actions in these patients. Although rTMS has shown benefits in civilian populations, "veterans may experience a different treatment response compared with civilians," the researchers, led by Jerome Yesavage, MD, Stanford University School of Medicine, Palo Alto, California, note.

The current trial, they add, is the first large-scale clinical trial that has examined the efficacy of rTMS in veterans with TRD.

Participants included 164 veterans with TRD from nine Veterans Affairs medical centers. Of the participants, 49% also had PTSD, and 54% had substance use disorder. Eighty-one patients were randomly allocated to receive left prefrontal rTMS (10 Hz; 120% motor threshold; 4000 pulses/session), and 83 to sham (control) rTMS for up to 30 sessions.

There was no significant effect of rTMS compared with sham treatment on the primary outcome of remission (odds ratio, 1.16; 95% confidence interval, 0.59 - 2.26; P = .67), the researchers report.

At the end of the acute treatment phase, 33 of 81 (40.7%) of those in the active rTMS group achieved remission of depressive symptoms, as did 31 of 83 (37.4%) of those in the sham treatment group. The overall remission rate was 39% (64 of 164). Remission rates were lower in patients with comorbid PTSD in both active and sham rTMS groups.

"This finding is consistent with the observation that placebo response has been increasing over time in clinical trials of antidepressant medication," the researchers note.

"These high remission rates suggest that veterans' expectations of improvement and extensive attention provided by the rTMS treatment team may have played a large role in the significant clinical improvements they experienced....

"Given this widespread use of rTMS in civilian populations and the high overall remission rates observed in this study, it would seem to be reasonable to use rTMS treatment in veterans," they add.

Puzzling Findings

The results of this study are "puzzling" for several reasons, Charles Nemeroff, MD, PhD, of the Miller School of Medicine, University of Miami, Florida, writes in an accompanying editorial.

First, the remission rates are "unusually high," he noted, especially in a treatment-resistant population and especially compared with other studies in similar populations, including the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study.

Second, the lack of efficacy for rTMS is in "sharp contrast" with prior studies in TRD.

Nemeroff believes several factors may explain the findings in this new study. First, the population is largely male, in contrast to most clinical trials involving depression, for which, typically, two thirds of the participants are female.

The psychological benefits of participation in clinical trials are another factor. "The repeated engagement of the subjects by the treatment team is not a neutral experience but tantamount to at least supportive psychotherapy, if not more," Nemeroff notes.

He adds that this is "an important negative study, but it does not fully answer the question of what the appropriate role for rTMS is in the treatment of TRD in veterans.

"As personalized medicine in psychiatry progresses, we will likely someday soon be able to accurately identify the best treatment for individual patients. This will likely involve both genomic markers as well as functional brain imaging predictors of response," Nemeroff writes.

This research was funded by the Cooperative Studies Program, Office of Research and Development, US Department of Veterans Affairs. The authors have disclosed no relevant financial relationships. Dr Nemeroff has received consulting fees from Xhale, Takeda, Taisho Pharmaceutical Inc, Bracket (Clintara), Fortress Biotech, Sunovion Pharmaceuticals Inc, Janssen Research and Development LLC, Magstim Inc, Navitor Pharmaceuticals Inc, TC MSO Inc, and Intra-Cellular Therapies, Inc.

JAMA Psychiatry. Published online June 27, 2018. Abstract, Editorial


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: