For the roughly one in three people with depression whose symptoms persist through antidepressants, the standard next step has typically meant clinic appointments, waiting lists, and treatments most people can’t easily access but a trial conducted entirely from participants’ homes suggests that a 30-minute daily session with a mild electrical headset may be a workable alternative.
tDCS has been studied in depression for over two decades. The technique uses mild milliampere currents applied at the scalp to modulate cortical excitability, and is low-cost, noninvasive, and has minimal side effects. The rationale for targeting the dorsolateral prefrontal cortex (DLPFC) in depression rests on the observation that this region — involved in mood regulation and cognitive control tends to show reduced activity in people with the disorder. Research has suggested tDCS modulates DLPFC-involved networks by inducing changes in cerebral blood flow and neurostructural plasticity at the target region, with these effects linked to alterations in neurotrophic factors such as brain-derived neurotrophic factor (BDNF) in patients with major depressive disorder.
At the neurotransmitter level, research has found that anodal tDCS applied to the left DLPFC affects GABA and dopamine in the striatum, and additional work shows tDCS can influence serotonin and noradrenaline release — all neurochemical systems implicated in depression. Despite this mechanistic rationale, results across clinical trials had been mixed before this study, with some trials showing significant antidepressant effects and others finding no advantage over sham.
Scientists approved the device. Not all scientists agreed.”
How the Study Was Conducted
The trial enrolled 174 participants — 120 women and 54 men — aged 18 or older, all in a current depressive episode of at least moderate severity as measured by the Hamilton Depression Rating Scale (mean baseline score: 19.07 ± 2.73). Participants were randomly assigned to active tDCS (n = 87, mean age 37.09 years) or sham (n = 87, mean age 38.32 years).
Each session lasted 30 minutes. The anode was placed over the left DLPFC and the cathode over the right DLPFC. Active tDCS delivered 2 milliamps; the sham device delivered 0 milliamps but included a brief ramp-up and ramp-down sequence to mimic the sensation of real stimulation. The protocol consisted of five sessions per week for the first three weeks, then three sessions per week for the remaining seven weeks, followed by a ten-week open-label phase. The trial was conducted entirely remotely, across multiple sites, with no requirement for clinic attendance.
What the Results Showed
Depressive symptoms showed significant improvement on the Hamilton Depression Rating Scale. The active group achieved a mean improvement of 9.41 ± 6.25 points, compared to 7.14 ± 6.10 points in the sham group (95% confidence interval: 0.51–4.01; P = 0.012). There were no differences in discontinuation rates between the two groups.
Symptom reductions in the active group appeared as early as three weeks into the protocol, and active tDCS produced two to three times higher remission and response rates compared to sham.
These results supported a regulatory outcome: in December 2025, the US Food and Drug Administration approved the Flow FL-100 — the first at-home tDCS device for the treatment of moderate to severe major depressive disorder in adults — marking the first time US clinicians could prescribe a fully remote, non-drug neuromodulation therapy for depression.
Evidence From Neuroimaging Studies
The Nature Medicine trial measured clinical outcomes but did not directly assess brain changes. A separate Scientific Reports study using longitudinal structural MRI in a randomized tDCS trial provides relevant mechanistic context. In that study, significant gray matter changes were observed in the left DLPFC in patients who received active high-definition tDCS compared to sham. A follow-up analysis within treatment groups found gray matter increases in regions functionally connected with the stimulation target, including bilateral DLPFC, bilateral posterior cingulate cortex, subgenual anterior cingulate cortex, and the right hippocampus, thalamus, and left caudate. The researchers interpreted this as evidence that serial stimulation can produce measurable neurostructural plasticity that extends across connected brain networks — though notably, no such changes were observed with conventional (non-high-definition) tDCS configurations in that study.
A separate randomized trial published in JAMA Network Open examined whether combining tDCS with repetitive transcranial magnetic stimulation (rTMS) would improve outcomes. In a 240-participant trial, those who received active tDCS combined with active rTMS showed greater reductions on the Hamilton Depression Rating Scale than those receiving either stimulation method alone, or sham versions of both, after two weeks of treatment.
Scientific Debate Around the FDA Approval
The FDA approval was not without controversy. A commentary published in The Lancet Psychiatry argued that the scientific evidence for tDCS efficacy is not yet convincing, and raised concerns that possible risks from misuse and unsupervised application in moderate to severe depression had not been adequately addressed. The authors of that commentary did not dispute the trial data but questioned whether the existing evidence base primarily from phase 2 trials meets the bar for widespread clinical use without closer monitoring.
The Nature Medicine trial was a phase 2 study, designed primarily to establish efficacy and safety signals rather than serve as a definitive confirmatory trial. The participant population people experiencing a current depressive episode of at least moderate severity may not represent the full range of people with depression. The sham blinding was achieved through sensation mimicry rather than electrode placement differences, and the researchers did not report whether participants successfully guessed their assignment, which is a standard concern in brain stimulation trials. Longer-term durability of symptom improvement beyond the ten-week open-label follow-up was not assessed. Individual response varied considerably, and the researchers noted that neuroimaging-guided personalization of stimulation targeting may be necessary to improve consistency across patients. Whether results generalize across different demographic groups, or to people who have not previously tried antidepressants, also remains to be established.
REFERENCES:
Woodham, R.D., Selvaraj, S., Lajmi, N., et al. “Home-based transcranial direct current stimulation treatment for major depressive disorder: a fully remote phase 2 randomized sham-controlled trial.” Nature Medicine, vol. 31, pp. 87–95, January 2025. DOI: 10.1038/s41591-024-03305-y.
Jog, M.A., et al. “Transcranial direct current stimulation (tDCS) in depression induces structural plasticity.” Scientific Reports, 2023. DOI: 10.1038/s41598-023-29792-6. | Zhou, D., et al. “Transcranial Direct Current Stimulation Combined With Repetitive Transcranial Magnetic Stimulation for Depression.” JAMA Network Open, 2024. DOI: 10.1001/jamanetworkopen.2024.44306. | Commentary: The Lancet Psychiatry, April 2026. DOI: 10.1016/S2215-0366(26)00092-1.
