The Trial Behind the Approval: Stronger Results With a Longer Course
REVIEW OF: Woodham RD et al, Nature Medicine 2025;31:87–95
STUDY TYPE: Randomized, double-blind, sham-controlled trial
EVIDENCE GRADE: High (9/10) (points off for unblinding)
Background
The FDA recently approved two wearable neuromodulation devices for depression. Flow activates the brain using transcranial direct current stimulation (tDCS). ProLivRx takes a different approach, activating sensory nerves that feed into the brain. Although its approval is based on less data, ProLivRx worked after antidepressants failed, while Flow and tDCS have little-to-no benefit in those more difficult cases.
Neuromodulation uses magnetic or electrical energy to activate neurons. Earlier devices were cleared by the FDA, while these new devices are fully approved — a higher bar of evidence to pass. They are also the first devices for home use, while the others require treatment in the office or even surgical implantation.
Earlier neuromodulation devices include transcranial magnetic stimulation (TMS), vagal nerve stimulation (VNS), deep brain stimulation (DBS), and electroconvulsive therapy (ECT). Each of these has unique mechanisms and roles. TMS uses magnets, while ECT induces seizures with electrical current, and only ECT reliably works in psychotic depression. tDCS uses a low-level, constant electrical current. Unlike ECT, it does not induce seizures, and unlike TMS it does not repolarize neurons.
Since it was developed in the 1960’s, tDCS has been tested in over 30 controlled trials of depression involving over 1,000 patients. Some are positive, some negative, but when meta-analyzed together they suggest a modest effect size (0.24-0.46), on par with antidepressants. When compared head-to-head with antidepressants, tDCS is equal, but it did not clearly work after antidepressants failed.
The FDA approval was based on those earlier trials and a single new trial that was sponsored by Flow’s manufacturer. This trial tested the device for ten weeks, as some trials that lasted only 4-6 weeks did not show a benefit.
The Study
174 adults with moderate-to-severe major depression (mean HDRS 19) were randomized to active or sham (ie, placebo) tDCS using the Flow FL-100 headset, worn at home for 30-minute sessions five times weekly for three weeks, then three times weekly for seven more. About two-thirds were on stable antidepressants; one-third were treatment-free. All visits were conducted remotely via videoconference.
At ten weeks, active tDCS produced a 9.41-point HDRS drop versus 7.14 for sham — a 2.27-point therapeutic gain (Cohen’s d effect size = 0.37). Remission rates were meaningfully higher: 45% versus 22%. Response rates on the MADRS told a similar story, with active treatment achieving roughly double the remission rate of sham across multiple scales. Blinding was imperfect — 78% of active participants guessed correctly — though outcomes held up even accounting for this. Skin redness was more common in the active group (64% versus 18%); two participants reported minor electrical burns from inadequate electrode moistening, both resolved without scarring.
Practice Implications
- We’ve known that tDCS treats depression, but the approval of Flow brings a reliable device and potential insurance coverage
- Although it doesn’t bring new efficacy beyond that of antidepressants, it brings a new approach that will appeal to patients who want to use an at-home device and avoid medication side effects
- tDCS has also shown efficacy in bipolar depression, but it can cause mania or hypomania in approximately 1 in 30 people (ProLivRx is not known to cause this)
- Beyond depression, tDCS has efficacy in OCD, substance use disorders, and cognitive deficits in schizophrenia.
- I’m more excited about ProLivRx, which is better tolerated, has a larger effect size, and works when antidepressants fail
- The FDA explicitly restricts Flow to patients who are not treatment-refractory to medication—an unusual approach that positions tDCS as an early-line intervention rather than a last resort
- Expect Flow to be available by Summer 2026
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
Share Your Input in Comments
- Have your patients tried tDCS? What struggles and successes have they seen?
- What role do you see for Flow in practice?
