This post originally appeared on MedScape.
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 City, told Medscape Medical News.
“In a presumably treatment-resistant population, the efficacy compared favorably with virtually all pharmacologic treatments” tested in the studies, said 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 (APA) 2021 Annual Meeting and was previously published in the Journal of Affective Disorders.
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 5010 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 3000 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 3814 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 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.
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 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. Sackeim said he plans to look more closely at outcomes of women in comparison with men.
The finding of a significant positive effect on aging contrasts with earlier research suggesting that age was a negative predictor. This, said 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 4000 or more pulses, said 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 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 session “may induce longer benefit,” he added.
Expanded Use Warranted?
The intervention proved very safe. Side effects, including headaches, were minimal, and there were “virtually no cognitive effects,” said Sackeim.
Sackeim believes TMS, as it has evolved, “is an outstanding option for treatment-resistant depression and it has a very bright future” and should not be reserved for patients with established treatment-resistant depression (TRD), which is the current US Food and Drug Administration indication.
“Restricting it to TRD in my mind is probably a mistake. Why shouldn’t the patient who is just starting on their course of treatment for depression have this as a nonpharmacological option?” he said.
Limitations of the study included its open-label design and the fact that only patients’ age, gender, outcome scores, and TMS treatment parameters were recorded in the registry. Other clinical characteristics, including medication use, were unknown.
However, it’s presumed that most patients had TRD, because insurance reimbursement for TMS typically requires an extensive history of failed antidepressant treatment.
Commenting on the study for Medscape Medical News, Mark George, MD, professor and Layton McCurdy Endowed Chair in Psychiatry, the Medical University of South Carolina, Charleston, South Carolina, called the remission and response rates “remarkable.”
The study included a “huge sample size” of Americans suffering from depression “who have not responded to talking therapy or medications,” noted George.
“This real-world study shows how effective, safe, and important TMS is for depressed patients who do not respond to medications,” he said.
Neuronetics Inc supported the NeuroStar Advanced Therapy System Clinical Outcomes Registry, analysis of the registry data, and the drafting of this manuscript. Sackeim serves as a scientific adviser to LivaNova PLC, MECTA Corporation, and Neuronetics Inc. He receives honoraria and royalties from Elsevier, Inc. and Oxford University Press. He is the inventor on nonremunerative US patents for Focal Electrically Administered Seizure Therapy (FEAST), titration in the current domain in ECT, and the adjustment of current in ECT devices; each patent is held by the MECTA Corporation. He is also the originator of magnetic seizure therapy.
American Psychiatric Association (APA) 2021 Annual Meeting: Poster 5290. Presented May 3, 2021.
J Affect Disord. Published online December 1, 2020. Full text
This post originally appeared on MedScape.