Treatment with transcranial magnetic stimulation (TMS) has a robust effect for patients with major depressive disorder (MDD), results from a large registry study show.
From patient self-reports and clinician assessments, investigators found that TMS was “surprisingly effective” and “an eye-opener” for these patients, lead investigator Harold A. Sackeim, PhD, professor of clinical psychology in psychiatry and radiology, Columbia University, New York, told this news organization.
“In a presumably treatment-resistant population, the efficacy compared favorably with virtually all pharmacologic treatments” tested in the studies, said Dr. Sackeim.
He noted that the registry from which the data were obtained “is the largest for any treatment of depression, period.” These positive results suggest TMS should be considered a first-line treatment for MDD, he added.
The study was presented at the virtual American Psychiatric Association 2021 Annual Meeting and was previously published in the Journal of Affective Disorders.
Real-world study
Results of randomized clinical trials have shown that TMS is effective for episodes of MDD. However, the investigators note that there is a need to characterize and identify patient- and treatment-related clinical outcomes.
The study included 5,010 adult patients who had received a primary diagnosis of MDD and were treated at 103 practices in the United States. Participants completed the nine-item Patient Health Questionnaire (PHQ-9) at baseline and at least one other time following a TMS treatment.
The average baseline PHQ-9 score was 19.8, indicating moderate to severe symptoms. This was also reflected in a smaller sample that included Clinical Global Impressions–Severity (CGI-S) ratings by clinicians, mostly psychiatrists.
About two-thirds of the study population were women. The average age was about 50 years. Participants typically received about 30 TMS sessions over 7 to 8 weeks.
TMS targets tissue in the dorsolateral prefrontal cortex. The standard protocol involves administering “fast” or high-frequency (10-Hz) stimulation on the left side. Sometimes, slow-frequency stimulation on the right side is added. About 57% of patients were treated on the left side, and 43% were treated on both sides. Each session involved delivery of about 3,000 pulses.
In the analysis of patient self-reports (PHQ-9), the response rate, which was defined as resolution of 50% or more of symptoms, was from 58% to 69%. The remission rate, defined as becoming asymptomatic or having minimal symptoms, ranged from 28% to 36%.
Results were about 5% higher in the “completer” sample, which included 3,814 patients who received at least 20 treatments and who completed a PHQ-9 assessment at the end the treatment course.
The number of completers in the analysis was “massive,” said Dr. Sackeim. It’s “ten times larger than in any previous TMS study; all randomized trials have a couple of hundred subjects at most, so this is whopping.”
The results provide “a full snapshot” of TMS in the “real-world” community instead of in the “highly controlled” environment of most studies, he added.
Gender differences
The analysis that included CGI-S clinician measures yielded higher outcome estimates – 79% to 83% for the response rate, and 47% to 63% for the remission rate.
Women tended to have better clinical outcomes. “It appears to me that around age 50 is where you see the difference,” said Dr. Sackeim. “Among women, it looks like the older they get, the better the outcome, whereas men are not showing that type of positive aging effect.”
This difference might be due to hormonal changes associated with menopause and the fact that older men with depression may have had a stroke or brain lesion. Dr. Sackeim said he plans to look more closely at outcomes of women in comparison with men.
This, said Dr. Sackeim, illustrates how rapidly the TMS field is evolving.
He noted that researchers are now personalizing the procedure by determining the optimal target for individual patients. Other investigators are testing different protocols.
In the current study, results tended to be better for those who received 4,000 or more pulses, said Dr. Sackeim. “There was an indication of a dose response effect in terms of how many pulses per session,” he said.
The authors note that the study’s PDQ-9 response and remission rates indicate that clinical outcomes are comparable to those of the seven antidepressants studied in Level 2 of the large Sequenced Treatment Alternatives to Relieve Depression (STAR-D) trial.
Initial data for relapse in the study population are “encouraging,” said Dr. Sackeim. “You don’t see the rapid relapse that you do when you discontinue some treatments, for example with ECT [electroconvulsive therapy].”
The “slower onset of action” over the course of several sessions “may induce longer benefit,” he added.