Nancy A. Melville

June 07, 2012

June 7, 2012 (Phoenix, Arizona) — Repetitive transcranial magnetic stimulation (rTMS) may offer an effective treatment option for patients with treatment-resistant depression, results of a new metaanalysis suggest.

Results of a new metaanalysis that included 15 studies suggest remission rates in patients with treatment-resistant depression were 6 times greater than those who received sham treatment.

"Relative to sham control, rTMS provided better outcomes for all measures that were assessed," said lead researcher Bradley N. Gaynes, MD, MPH, a professor of psychiatry at the University of North Carolina School of Medicine, in Chapel Hill, North Carolina. "I was surprised at the results. The effect size was similar to what you would see with antidepressants, and this group was treatment-resistant," he added.

The analysis included studies conducted between 1980 and 2011 with an average duration of treatment of 40 minutes daily for 2 to 6 weeks.

The researchers evaluated data including patient population, settings, funding, study design, risk of bias for each study, and outcomes, which included severity of depressive symptoms, response rate, and remission rate.

Long-term Effect Unclear

The results showed that rTMS provided a significant decrease in disease severity, represented in a decline in the Hamilton Rating Scale for Depression (HAM-D) of more than 5 points, compared with sham control. A minimum threshold of a 3-point HAM-D difference is considered to be clinically meaningful, the authors noted.

In addition, patients receiving rTMS were 3 times more likely to experience a reduction in depressive response vs those receiving a sham procedure.

Participants receiving rTMS were also more than 6 times as likely to achieve remission compared with the groups receiving sham treatment. Remission rates with rTMS, reported in 5 of the trials, ranged from 10% to 57%, whereas the remission rates for the sham treatment ranged from 0 to 20%, with most between 0 and 5%.

Dr. Gaynes noted that the analysis had several limitations, including the fact that it did not take into account the number of treatment failures and that follow-up periods were relatively short — usually between 2 and 5 weeks.

"It's important to realize that these were short-term studies, and we do not know how long the recovery persisted."

Improved Controls

Studies comparing rTMS to a sham treatment have faced some criticism in the past, but the analysis included improved controls, Dr. Gaynes said.

"There was some difficulty in the past in identifying what a reasonable sham control for rTMS was," he explained. "Early on, the sham controls were not as effective, but in more recent studies, they had developed more effective controls."

"When we looked at the relative odds of remission in the study with the highest quality sham, it was similar to what our metaanalysis found, although their number needed to treat was higher, reflecting an overall lower remission rate in their study of 14% rTMS vs 5% sham."

Dr. Gaynes said the findings underscore its potential benefits for the many patients who fail to respond to depression treatments.

"As many as 50% of patients who receive adequate aggressive antidepressant trials fail to recover after 2 trials, leaving a large population that meet criteria of treatment-resistant depression, and the likelihood of recovering after those 2 failed trials drops dramatically," he said.

"rTMS is not approved for treatment-resistant depression; however, it may be a reasonable option for this group, especially if medication side effects are a substantial concern, because it appears to be well tolerated."

Few Treatment Options

According to Paul E. Holtzheimer, MD, a nonpharmaceutical option for treatment-resistant depression is welcome, because results with additional medication are not always successful.

"There are not a lot of evidence-based options for treatment-resistant depression," said Dr. Holtzheimer, an associate professor of psychiatry and surgery and director of the Mood Disorders Service at Dartmouth Medical School and Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire.

"There are several medications that can be used in augmentation, like lithium or atypical antipsychotics, and there is reasonably good data for each of those in patients that failed 1 treatment, but even the data with those suggests the response rates aren't terribly high," he told Medscape Medical News.

"They're better than placebo, but we're not getting everybody better just by adding another medication."

"TMS hasn't been adequately compared to those, so we really don't know how it compares."

Electroconvulsive therapy (ECT) is another nonpharmaceutical option for treatment-resistant depression, and Dr. Gaynes' study was part of a larger review that also compared rTMS with ECT. However, the strength of evidence in the studies evaluated was considered low.

Overall, the findings are fairly consistent with previous research on rTMS, Dr. Holtzheimer said.

"TMS does have statistically significant antidepressant effects both in terms of response and remission rates as well as a decrease in depression severity," he said.

"Most would say it also probably has clinically significant effects as well, but this has been questioned, and we're still kind of watching it and trying to find ways to improve it."

The study was supported by the National Institute of Mental Health and the Agency for Healthcare Research and Quality. Dr. Gaynes has disclosed no relevant financial relationships. Dr. Holtzheimer is a consultant for Medical Neuromodulation and Cervel Neurotech. Dr. Holtzheimer reports that he has received an honorarium for giving a talk to investigators at a Johnson and Johnson symposium on mood disorders.

New Clinical Drug Evaluation Unit (NCDEU) 52nd Annual Meeting. Abstract presented May 20, 2012.


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