Noninvasive transcranial alternating current stimulation (tACS) may lead to rapid improvement in major depressive disorder (MDD), results of a randomized, sham-controlled trial suggested. However, independent experts said more research is needed to confirm its benefit.
While both the active and sham tACS groups exhibited similar clinically significant improvements in self-reported depression severity, post hoc analyses showed active tACS was superior to sham in women and in those with high adherence to treatment.
"We can feel reasonably confident that tACS is an effective treatment for people with MDD, particularly for women, as long as people use it consistently," study investigator Philip Gehrman, PhD, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, told Medscape Medical News.
"Improvements in depression were seen as early as the first week of treatment, and these benefits were maintained for the duration of the study," added co-investigator Kyle Lapidus, MD, PhD, with Affective Care in New York City.
The study was published online April 22 in the Journal of Clinical Psychiatry.
Seeking FDA Approval
tACS is a form of wearable noninvasive brain stimulation that delivers a low intensity, pulsed, alternating current via scalp electrodes. The current study utilized the OAK (version 2.0) tACS device from Fisher Wallace Laboratories, which funded the study.
A total of 255 adults (185 women) meeting the criteria for MDD and having a score on the Beck Depression Inventory, Second Edition (BDI-II) between 20 and 63 (mean score, 34) were randomly allocated to at-home active or sham tACS for two, 20-minute treatment sessions daily for 4 weeks.
Both treatment groups showed similar clinically significant improvements in mean BDI-II scores at week 2 compared with baseline (the primary efficacy outcome), with no significant difference between groups (P = .056).
Post hoc analysis of participants with 100% compliance in the first 14 days showed a significantly greater improvement in BDI-II scores at week 2 in the active vs sham tACS group (P = .005), and this was true at 1 week (P = .022) and 4 weeks (P = .018).
In preplanned subgroup analyses, treatment effects were greatest among women for whom active tACS was superior to sham tACS across time points.
"Active tACS greatly exceeded the 17.5% threshold of minimally clinically important within-group difference established for the BDI-II. Side effects were minimal and mild," the authors reported in their article.
"The speed of response is also impressive and suggests that tACS may be able to provide rapid relief in depression with very limited side effects. Given the risks associated with unmanaged MDD, rapid relief is essential," said Lapidus.
The researchers noted that the large improvements in the sham group make it tough to know how much of the treatment effect was due to the direct effects of the tACS device vs placebo effects. Having participants in both groups engage in 20 minutes twice daily of calm activities during active and sham tACS may itself have therapeutic benefits irrespective of tACS.
Limitations of the study include reliance on self-reported patient outcome measures and the relatively short 4-week treatment period.
"The next step is to do a longer study to prove the duration of efficacy of tACS in MDD is longer than 4 weeks," study investigator Eric Bartky, MD, with Bartky HealthCare Center, LLC, Livingston, New Jersey, told Medscape Medical News.
On that front, Fisher Wallace said a new 12-week study using their tACS device was designed by Maurizio Fava, MD, psychiatrist-in-chief at Massachusetts General Hospital, Boston, to assess the durability and effectiveness of treatment in men and women. The company intends to use the results of this 12-week study to seek US Food and Drug Administration (FDA) approval.
Promising but Preliminary
Reached for comment, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Canada, and head of the Mood Disorders Psychopharmacology Unit, said the efficacy being reported with tACS is "promising but needs to be replicated in a much larger study."
McIntyre, who wasn't involved in the study, told Medscape Medical News tACS is "an interesting approach, not only from the point of view of the therapeutic, but also the ecosystem. There is interest in identifying ways to improve access and availability to treatment for depression. Clearly that is the major problem confronting many Americans."
"If we can democratize the access and have home-based care, that clearly would be an improvement over status quo, but, of course, it will need to be guided by best practices, safety, and efficacy, and I look forward to seeing more studies with it," McIntyre added.
Flavio Frohlich, PhD, professor, Department of Psychiatry, University of North Carolina (UNC) at Chapel Hill and director of the Carolina Center for Neurostimulation, also emphasized the need for more study.
"In general, having portable, low amplitude, electric brain stimulation devices for psychiatric indications is really exciting. However, this study misses some of the things that we would typically see in gold standard clinical trials of depression treatments," Frohlich, who also wasn't involved in the study, told Medscape Medical News.
One is sole reliance on self-report. "While it's important to get self-reports from patients, what we're usually looking for is a clinician-administered rating scale, such as the Hamilton Depression Rating Scale, which would offer some more reassurance," Frohlich said.
"It's also important to note that the main analysis did not show a statistically significant difference between the active and the placebo group. There were some interesting exploratory findings, but overall, I would be very cautious in drawing major conclusions from it. It's clear that much more study is needed," Frohlich added.
The study was sponsored by Fisher Wallace Laboratories Inc. Gehrman, Lapidus and Bartky disclosed financial relationships with the company. McIntyre received speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, and Atai Life Sciences. McIntyre is a CEO of Braxia Scientific Corp. Frohlich is the lead inventor of intellectual property issued to UNC and licensed to Electromedical Products International (EPI) and has participated in research involving a separate tACS device for treatment of depression. In the last 12 months, he received consulting honoraria from EPI and Insel Spital and royalties from Academic Press and the University of North Carolina at Chapel Hill.