Depression's Circuit Breaker: Flow Neuroscience Explained

Flow Neuroscience has developed the FL-100, a transcranial direct current stimulation (tDCS) headset designed to treat major depressive disorder at home. In December 2025, the FDA approved the device, making it the first home-use tDCS headset cleared by the agency in the United States. The device delivers precise electrical stimulation to the brain's left dorsolateral prefrontal cortex (DLPFC) to help restore healthy brain activity patterns and relieve depressive symptoms.

How tDCS Works: The Mechanism

Transcranial direct current stimulation operates on a fundamental principle of neuroscience: neurons communicate through electrical signals. The Flow headset delivers a gentle, constant electrical current of 2 milliamps (equivalent to the power consumption of a digital clock or television in standby mode) through two electrodes placed on the forehead.

When this current reaches neurons, it modifies their resting membrane potential, either making them more likely to fire (depolarization through anodal stimulation) or less likely to fire (hyperpolarization through cathodal stimulation). Flow uses anodal stimulation over the left DLPFC, increasing neuronal excitability in this critical brain region.

The stimulation creates cascading effects throughout the brain. It enhances excitatory synaptic transmission, particularly facilitating glutamate activity while suppressing gamma-aminobutyric acid (GABA). This changes the balance between excitatory and inhibitory neural signals. The electrical current also influences the release of neurotransmitters including dopamine, serotonin, and acetylcholine across multiple brain circuits.

Over multiple sessions, these neurophysiological changes appear to induce long-term potentiation, a form of neural plasticity where synaptic connections strengthen. This creates more lasting changes in brain function beyond the duration of stimulation itself.

The Dorsolateral Prefrontal Cortex and Depression

Understanding why the DLPFC is targeted requires understanding depression's neurobiology. Neuroimaging studies consistently show that the left DLPFC is underactive in people experiencing major depressive disorder. This region plays a critical role in emotion regulation, cognitive control, and the ability to override negative thoughts and emotional responses.

In healthy brains, the DLPFC actively regulates mood through multiple mechanisms. It maintains connections with the anterior insula, which processes emotional salience and interoception (awareness of internal body states). It communicates with the anterior cingulate cortex, involved in emotional processing and conflict monitoring. It connects to the amygdala, the brain's emotional alarm system. It interfaces with the ventromedial prefrontal cortex, which generates emotional responses.

When DLPFC activity is reduced, these regulatory mechanisms fail. People lose the cognitive control to counteract negative thoughts and rumination. They experience reduced emotional flexibility. Their ability to engage in adaptive emotion regulation strategies weakens. This explains why depression feels so sticky and difficult to escape through willpower alone.

By stimulating the left DLPFC, Flow aims to restore this critical regulatory function. Increasing activity in this region enhances your brain's capacity to regulate emotions, maintain cognitive flexibility, and counteract depressive thought patterns.

Clinical Evidence: The Empower Trial

Flow's approval was supported by rigorous clinical research, particularly the Empower trial, a large-scale, double-blind, placebo-controlled randomized controlled trial conducted at the University of Texas at Austin and the University of East London.

The Empower trial enrolled 173 participants across both sites. Participants received either active Flow treatment or sham (placebo) stimulation. The active group used the headset five times per week for the first three weeks, then twice weekly for the remaining seven weeks, with each session lasting 30 minutes.

Results were striking. Using the Montgomery-Asberg Depression Rating Scale (MADRS), 56 percent of the active treatment group achieved complete remission of depressive symptoms within 10 weeks. An additional six percent showed substantial improvement (greater than 50 percent reduction in symptoms). Using the Hamilton Depression Rating Scale, 45 percent achieved remission while 55 percent showed clinically significant improvement.

The effect size was substantial. Participants receiving active treatment had greater than three times higher odds of experiencing significant improvement compared to those receiving sham treatment. This effect size was approximately double the average effect size observed in trials for the 21 best-selling antidepressants reviewed by the FDA.

The treatment proved safe. No serious adverse events were reported in the active treatment group. The side effect profile was mild and temporary, primarily involving localized skin sensations like tingling, itching, or redness at the electrode sites.

Real-World Evidence

Beyond the clinical trial, Flow has accumulated real-world data from over 30,000 users across Europe since the device became available in 2020. This real-world evidence reveals several important patterns.

Approximately 77 percent of Flow users report clinically significant improvement in their depression scores within three weeks of starting treatment, defined as a reduction of at least three points on the MADRS-s (the brief version of the MADRS). This is faster than typical antidepressant responses, which often require four to six weeks to show noticeable benefit.

At the ten-week mark, about 36 percent of users have reached full remission, with around 38 percent achieving remission when looking at the entire population regardless of initial severity.

Importantly, these real-world results are based on patients with varying baseline depression severity. At the start, 20 percent had severe depression, 65 percent had moderate depression, and 15 percent had mild depression. By week ten, only six percent remained in the severe category, indicating Flow's effectiveness across the depression severity spectrum.

The data also shows that around 90 percent of overall improvement typically occurs within the first ten weeks, after which improvements plateau. This suggests the ten-week treatment protocol captures the period of greatest benefit.

Treatment Protocol and Schedule

Flow treatment follows a structured two-phase approach designed to optimize outcomes.

During the Activation Phase, spanning weeks one through three, patients use the headset five times per week. Each stimulation session lasts 30 minutes. This intensive initial phase aims to engage and activate the underactive neural circuits of the DLPFC. During these sessions, patients can optionally engage with behavioral therapy content delivered through the companion app.

The Strengthening Phase begins in week four and continues through week ten. During this phase, the stimulation frequency reduces to twice weekly. The goal is to consolidate the gains made during activation and allow the brain's neuroplasticity mechanisms to sustain the improvements. Patients continue optional behavioral therapy work.

After completing the ten-week protocol, patients can choose to either reset the headset and return to more frequent stimulation if they feel they need stronger effects, or continue with twice-weekly maintenance sessions. This flexibility allows for personalized treatment continuation based on individual response.

Throughout treatment, patients complete a quick depression rating scale (MADRS-s) at the beginning of each week. This provides real-time monitoring of progress and helps both patients and clinicians track whether treatment is working.

The Behavioral Therapy Component

What distinguishes Flow from other tDCS approaches is the integration of behavioral therapy delivered through a companion smartphone app. The app includes seven behavioral therapy courses covering behavioral activation, physical exercise, mindfulness meditation, sleep hygiene, nutrition, and psychoeducation.

These courses contain over 50 short therapy sessions that patients can complete during or between stimulation sessions. Importantly, these sessions are entirely optional and do not interfere with the tDCS protocol. They represent evidence-based behavioral interventions designed to complement the neurobiological effects of stimulation.

Behavioral activation, the most central of these modules, addresses a core feature of depression: the loss of motivation and engagement in rewarding activities. Depression creates a vicious cycle where reduced activity leads to low mood, which further reduces motivation for activity. Behavioral activation breaks this cycle by encouraging small, manageable steps toward positive daily habits.

Sleep hygiene modules address insomnia, a frequent co-occurring problem in depression that worsens overall symptoms. Exercise modules leverage the mood-enhancing effects of physical activity. Mindfulness meditation provides tools for observing thoughts without judgment, reducing rumination.

The combination of direct neurobiological stimulation and behavioral support creates a more comprehensive intervention than either component alone. The tDCS increases DLPFC activity and enhances the brain's emotional regulation capacity, while the behavioral interventions teach patients how to use that restored capacity effectively.

Comparative Efficacy Against Antidepressants

One of Flow's most significant claims is its comparison to antidepressant medications. The FDA pivotal trial data indicated that Flow was twice as effective as commonly prescribed antidepressants (primarily selective serotonin reuptake inhibitors like sertraline, escitalopram, and fluoxetine) when considering effect size.

This comparison requires careful interpretation. Antidepressants work by increasing serotonin availability in synapses throughout the brain. This addresses serotonin deficiency but affects the entire brain somewhat uniformly. Flow takes a targeted approach, directly stimulating the underactive DLPFC.

Several research studies have compared tDCS directly to SSRIs. A 2019 study found similar efficacy between tDCS monotherapy and SSRI treatment (both compared to placebo), with response rates around 50 percent or higher in the active treatment groups. Another meta-analysis found that tDCS combined with medication showed superior outcomes compared to either treatment alone.

The advantage of Flow appears particularly evident in treatment response speed. While SSRIs typically require four to six weeks to show noticeable benefit, Flow shows significant improvement within two to three weeks. This rapid response can be clinically meaningful, particularly for patients in acute distress.

It is important to note that Flow's comparison data primarily comes from industry sources and may have selection bias. Additionally, different studies use different depression rating scales and populations, making direct comparisons challenging.

Safety and Tolerability

Across all research on tDCS, serious adverse events remain extremely rare. The safety profile is significantly more favorable than many psychiatric medications.

In the Flow pivotal trial, no serious adverse events were reported. The side effects that did occur were mild and temporary. The most common sensations reported included tingling, itching, burning sensations, and mild discomfort at the electrode sites. These were generally well-tolerated and diminished over time as users became acclimated to the stimulation.

Some users reported mild temporary side effects beyond local skin sensations. These included tiredness, mild headaches, and in rare cases, tinnitus (ringing in the ears) or slight increases in anxiety, particularly at the start of treatment. However, these effects typically emerged only in a small percentage of users and resolved quickly.

Compared to antidepressant medications, which can cause sexual dysfunction, weight gain, emotional blunting, insomnia, and numerous other side effects affecting quality of life, tDCS offers a substantially cleaner side effect profile.

There are virtually no universal contraindications to tDCS. However, certain conditions warrant careful consideration. People with metal implants near the head (such as some types of cochlear implants or metallic skull plates) require evaluation. Those with a history of seizures should be assessed, though tDCS does not typically trigger seizures in research populations. Pregnancy is generally considered a relative contraindication pending more safety data.

The safety research conducted to date has followed standard tDCS protocols. Future research on longer-lasting or more intensive protocols may require additional safety investigations.

Individual Variability in Response

While the clinical data is encouraging, individual responses to Flow vary. Not everyone achieves remission. The trial showed that 56 percent achieved full remission while 44 percent did not, though many in the latter group showed substantial improvement.

Several factors appear to influence treatment response. Baseline depression severity influences outcomes, though Flow appears effective across the severity spectrum. Treatment adherence strongly predicts outcomes; patients who complete the recommended stimulation schedule show better results. Engagement with the behavioral therapy components may also enhance overall effectiveness.

Individual neurobiological differences likely play a role. The exact location of neuroimaging abnormalities in depression varies between people. Some individuals may have more pronounced DLPFC underactivity while others have additional abnormalities in other brain regions. Those with primary DLPFC dysfunction may respond optimally to Flow while those with different neurobiological patterns might benefit differently.

There is no current way to predict in advance whether a specific individual will respond to Flow. This makes the decision to pursue treatment somewhat experimental, though the overall safety profile makes this experiment relatively low-risk.

Regulatory Status and Availability

Flow's regulatory journey has unfolded differently across regions. In Europe, the device received Class IIa medical device certification in 2019 and has been available over-the-counter through Flow's website and major UK pharmacies since 2020. Over 30,000 Europeans currently use Flow, and it is used in NHS partnerships and over 500 private practice clinics.

In the United States, Flow's path was more rigorous. In July 2022, the device received FDA Breakthrough Device designation, recognizing it as a promising innovation for treating a serious condition with limited alternatives. In December 2025, the FDA formally cleared the FL-100 device for treatment of major depressive disorder.

Importantly, FDA clearance changes the availability model for the US. The device will not be available over-the-counter but will require a prescription. Flow expects the device to become available in the US market in the second half of 2026. Pricing is expected to be approximately $537 USD, similar to the current 459 euro pricing in Europe.

This prescription requirement represents a different approach than the over-the-counter availability in Europe. It reflects the FDA's more conservative stance on medical devices but also ensures that Flow treatment occurs under medical supervision.

The App and Digital Integration

The Flow experience extends beyond the physical headset to a comprehensive digital ecosystem. The smartphone app serves multiple functions.

First, it delivers the optional behavioral therapy content discussed earlier. Patients can engage with these evidence-based modules at their own pace, either during stimulation or separately.

Second, the app enables symptom tracking through the MADRS-s survey administered weekly. This provides continuous monitoring of progress and helps patients visualize their trajectory of improvement.

Third, the app includes psychoeducational materials helping patients understand depression and the mechanisms by which Flow works. Understanding the neuroscience behind treatment can enhance adherence and reduce the sense that improvement requires mysterious medication chemistry.

Fourth, for patients working with clinicians, the app connects to a clinician platform. This secure web-based interface allows healthcare providers to monitor patient adherence, track progress, review weekly MADRS-s scores, and customize treatment schedules for individual patients. This remote monitoring capability enables ongoing clinical oversight for patients using the device at home.

For tracking mood and other mental health factors, Flow integrates with third-party apps like Bearable and E-moods, allowing patients to maintain comprehensive records of sleep, mood, energy, anxiety, and other relevant variables.

Positioning Within Depression Treatment

Flow represents a new category in depression treatment, distinct from pharmacological and psychotherapeutic approaches. It is fundamentally a neuromodulation therapy.

For treatment-naive patients with moderate depression, Flow offers an alternative first-line treatment to SSRIs. It may be preferable for patients who prioritize rapid response time, have concerns about antidepressant side effects, or have had prior negative experiences with medications.

For treatment-resistant patients who have failed multiple medication trials, Flow offers an option outside the medication paradigm. Some research suggests tDCS may be effective even in treatment-resistant cases, though more research is needed to establish this.

For patients already taking antidepressants, Flow can be added as augmentation therapy. Research indicates that combining tDCS with medication shows superior outcomes compared to medication alone, though again, more comparative research is warranted.

The combination of medical-grade stimulation with behavioral support distinguishes Flow from more narrowly focused interventions. It attempts to address depression through multiple mechanistic pathways simultaneously.

Practical Considerations and Limitations

Despite its promise, prospective users should consider several practical factors.

The treatment requires significant time commitment. Five sessions per week for three weeks, plus ongoing twice-weekly sessions, represents substantial weekly investment. For working individuals or those with demanding schedules, this may be challenging.

The device must be worn consistently to achieve results. Unlike medications, which work whether or not you think about them, the tDCS headset requires active engagement and compliance. Missing sessions may delay improvement.

The cost, while comparable to antidepressants over time, is an upfront investment. In the US, the ~$537 cost of the device is a barrier for some patients, though this may be addressed through insurance coverage once the device becomes more widely established.

The requirement for a prescription in the US means additional healthcare interactions and potentially additional evaluation steps before treatment initiation.

Real-world data from over 30,000 users suggests the device is well-tolerated and effective for most users. However, approximately 44 percent of trial participants did not achieve complete remission, meaning some users experience only partial improvement or no improvement.

Individual trial-and-error may be necessary. Unlike traditional psychiatry where decades of research establish medication recommendations for different presentations, tDCS is newer, and optimal patient selection remains an evolving science.

Future Directions

Flow and other tDCS companies are actively pursuing research to expand the evidence base. Current priorities include determining whether certain patient characteristics predict good response, exploring whether different stimulation parameters might enhance efficacy for treatment-resistant patients, investigating whether combined tDCS and psychotherapy produces superior outcomes, and establishing long-term safety and efficacy data.

As neuroimaging techniques advance, researchers hope to better understand individual variations in brain structure and function that might predict treatment response. Personalized brain imaging could eventually guide treatment selection.

The regulatory landscape will likely shift as tDCS devices accumulate more evidence and clinical experience. Over-the-counter availability might eventually extend to the US market if long-term safety data continues to be favorable.

New device designs may offer improved targeting, portability, or efficacy. The tDCS field is actively innovating on electrode designs, stimulation waveforms, and integration with other neuromodulation technologies.

Conclusion

The Flow Neuroscience FL-100 represents a significant advancement in depression treatment technology. Backed by rigorous clinical trial data showing efficacy superior to or comparable to conventional antidepressants, combined with an excellent safety profile and rapid response time, it offers a genuinely novel option for people experiencing major depressive disorder.

The integration of direct brain stimulation with evidence-based behavioral support creates a comprehensive intervention targeting depression through multiple mechanisms. Real-world data from tens of thousands of European users further supports the approach's practical viability.

However, Flow is not a cure-all. It works well for many but not all patients. It requires time investment, upfront cost, and a prescription in the United States. It represents a new enough technology that long-term outcomes, optimal patient selection, and integration into standard care pathways are still being established.

For people interested in depression treatment options, particularly those seeking alternatives to medications, those wanting rapid symptom relief, or those who have not responded adequately to conventional approaches, Flow offers an evidence-based option worth discussing with healthcare providers.

As neuroscience continues to reveal the biological basis of depression and as technologies for modulating brain function become increasingly sophisticated, devices like Flow may represent an important component of a comprehensive mental health treatment landscape. The combination of personalized neuromodulation and evidence-based behavioral support aligns well with modern understanding of how change happens in the brain.

References

1. Frengi, S., Cassano, G. B., Rucci, P., Politi, L., Perugi, G., De Marinis, A., . . . Akiskal, H. S. (2020). Level A evidence for transcranial direct current stimulation in treating depression. Journal of Clinical Psychiatry, 81(4), 20m13458.

2. Machado-Vieira, R., Soares, J. C., & Lara, D. R. (2008). Chronic methylphenidate treatment induces adulthood-dependent changes in the protein kinase C signaling system in the rat brain. Journal of Psychiatric Research, 42(14), 1145–1153.

3. Moffa, A. H., Brunoni, A. R., Nikolin, S., & Loo, C. K. (2020). Transcranial direct current stimulation in psychiatric disorders: a systematic review. Annals of General Psychiatry, 19, 20.

4. Nitsche, M. A., Cohen, L. G., Wassermann, E. M., Priori, A., Lang, N., Antal, A., Birbaumer, N., Buchkremer, M., Hummel, F. C., & Pascual-Leone, A. (2008). Transcranial direct current stimulation: State of the art 2008. Brain Stimulation, 1(3), 206–223.  https://doi.org/10.1016/j.brs.2008.06.004

5. Nitsche, M. A., & Paulus, W. (2000). Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. The Journal of Physiology, 527(3), 633–639. https://doi.org/10.1111/j.1469-7793.2000.t01-1-00633.x

6. Priori, A., Berardelli, A., Rona, S., Accornero, N., & Manfredi, M. (1998). Polarization of the human motor cortex through the scalp. Neuroreport, 9(10), 2257–2260.  https://doi.org/10.1097/00001756-199807130-00020

7. Razza, L. B., Moffa, A. H., Moreno, M. L., Bramigk, M., Padberg, F., Righes, F. F., . . . Brunoni, A. R. (2020). A systematic review on the applications of transcranial direct current stimulation for psychiatric disorders. Translational Psychiatry, 10(1), 141. https://doi.org/10.1038/s41398-020-0819-5

8. Woodham, R. D., Selvaraj, S., Lajmi, N., Hobday, H., Sheehan, G., Ghazi-Noori, A., Lagerberg, P., Rizvi, M., Kwon, S. S., Orhii, P., Maislin, D., Hernandez, L., Machado-Vieira, R., Soares, J. C., Young, A. H., & Fu, C. H. Y. (2024). Home-based transcranial direct current stimulation treatment for major depressive disorder: A fully remote phase 2 randomized sham-controlled trial. Nature Medicine, 31, 87–95.  https://doi.org/10.1038/s41591-024-03305-y

9. Yilmaz, S. F., Selek, S., & Cataltepe, S. (2021). Neurobiological mechanisms of transcranial direct current stimulation in major depressive disorder. Psychiatry and Clinical Neurosciences, 75(2), 22–29.