FDA Approves Proliv™Rx: A Milestone for At-Home Neuromodulation in Depression Care

Writer: Kaitlin Kinney

Editor: Sarah Sizer

Major depressive disorder (MDD) remains one of the most common and disabling mental health conditions worldwide, with an estimated 332 million people affected globally.1,2 While antidepressant medications and psychotherapy are effective for many individuals with MDD, approximately 30 to 40% of patients continue to experience persistent symptoms despite standard first-line treatment approaches.3 For individuals who do not respond adequately to initial therapies, additional interventions are available, including electroconvulsive therapy (ECT), ketamine-based treatments, and clinic-based neuromodulation approaches.3,4 In patients with treatment-resistant depression, these interventions can still provide meaningful benefit, with reported response rates of approximately 40 to 70% depending on the modality, patient population, and outcome definition.3,4

However, real-world access barriers, including time burden, treatment logistics, and insurance requirements, can limit feasibility for many patients who are resistant to first-line treatments.5,6 Notably, transcranial magnetic stimulation (TMS), one of the most widely used neuromodulation techniques for MDD, commonly requires documentation of multiple prior antidepressant failures (often up to ~4 trials) before authorization.7 These barriers can delay access to effective treatment, prolong symptom burden, and widen disparities in depression care.8

On December 31, 2025, the FDA granted Premarket Approval (PMA) for Neurolief’s Proliv™Rx neuromodulation system (P250010).9 The Proliv™Rx System provides focal external Combined Occipital and Trigeminal Afferent Stimulation (eCOT-AS) and is intended as an adjunctive treatment for MDD in adults who failed to achieve satisfactory improvement from at least one previous antidepressant medication, for use at home or in the clinic.9

A quick refresher: why does PMA matter?

If you have spent any time reading health news headlines, you have probably seen words like “FDA cleared,” “FDA approved,” or “FDA authorized” used somewhat interchangeably. However, in the medical device world, these terms reflect distinct regulatory pathways that differ in their evidentiary requirements.

Depending on a device’s risk level and intended use, the FDA may evaluate medical devices through several pathways, including 510(k) clearance for lower-risk devices that are substantially equivalent to existing technologies, De Novo classification for novel moderate-risk devices, and Premarket Approval (PMA) for the highest-risk (Class III) devices. 10

PMA is the process the FDA uses to evaluate high-risk medical devices for safety and effectiveness. 10 Unlike 510(k) clearance or De Novo classification, which rely primarily on demonstrating equivalence to existing devices or reasonable assurance of safety and effectiveness, the PMA pathway typically requires direct clinical evidence from well-controlled studies demonstrating a device’s safety and effectiveness for its intended use. 10 While PMA approval does not mean a device will work for every individual, it reflects the FDA’s highest level of clinical evidence required for medical devices.10

In that sense, Proliv™Rx is notable not only because it introduces a new neuromodulation option for MDD, but because it did so through the Class III PMA pathway, placing it firmly within a regulated medical treatment rather than a consumer “wellness” technology.10

What is Proliv™Rx?

Proliv™Rx is a wearable, non-invasive brain neuromodulation system designed for prescription use under physician direction.9 Unlike many neuromodulation therapies that rely on repeated in-clinic administration, Proliv™Rx is indicated for use both in the clinic and at home. 

Treatment with Proliv™Rx involves daily stimulation sessions, with each session lasting approximately 20 minutes, administered according to a prescribed treatment schedule.11 This at-home dosing model distinguishes Proliv™Rx from clinic-based neuromodulation approaches that often require frequent in-person visits over several weeks.

Proliv™Rx delivers external Combined Occipital and Trigeminal Afferent Stimulation (eCOT-AS), a neuromodulation approach designed to engage sensory afferent pathways arising from the trigeminal nerve (cranial nerve V) and occipital nerves.11,12 Using controlled pulses of electrical stimulation, eCOT-AS is applied across both the facial/forehead region and the posterior scalp/upper cervical region, thereby activating two distinct peripheral sensory input pathways that transmit signals into the central nervous system (Figure 1).11,12

Rather than directly stimulating cortical tissue, eCOT-AS is intended to modulate neural activity indirectly through ascending sensory afferent signaling. Through this mechanism, peripheral sensory inputs may influence distributed neural circuits involved in mood regulation, including circuits related to arousal and affective processing, though the precise downstream pathways and network effects remain under investigation.11,12 

Figure 1. Trigeminal and occipital afferent pathways targeted by eCOT-AS. External Combined Occipital and Trigeminal Afferent Stimulation (eCOT-AS) engages sensory afferent pathways arising from the trigeminal nerve (via the face and forehead; left panel) and occipital nerves (via the posterior scalp and upper cervical region; right panel). These peripheral sensory inputs transmit ascending signals into the central nervous system, providing an indirect neuromodulatory route to influence higher-order neural networks involved in mood regulation. Created in BioRender. Kinney, K. (2026) https://BioRender.com/vglrgx8.

Clinical evidence supporting approval: the MOOD Study

FDA approval was supported by evidence from the MOOD Study, a multicenter, randomized, double-blind, sham-controlled clinical trial evaluating home-based eCOT-AS therapy in adults with MDD whose depression had not adequately improved after antidepressant medication.11 Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17), a widely used clinician-rated measure of depression severity in clinical research.11

In the double-blind phase, active eCOT-AS demonstrated significantly greater improvement than sham at Week 8, with a mean HDRS-17 reduction of 8.6 points in the active group compared to 6.0 points in the sham group (p = 0.02).11 The study also reported significantly higher remission rates in the active treatment group (21.3%) compared with sham (6.0%, p = 0.03).11

The sham condition was designed to closely mimic the active intervention, helping preserve blinding and patient expectations, an important consideration in neuromodulation trials. As is common in depression studies, participants in the sham group showed meaningful symptom improvement, reflecting a substantial placebo response that can arise from factors such as treatment expectancy, structured daily routines, and increased clinical monitoring.3 Importantly, despite this robust sham response, active eCOT-AS produced significantly greater symptom improvement and remission rates, supporting a treatment effect beyond placebo.11

Scaling neuromodulation beyond the clinic

One of the most distinctive aspects of Proliv™Rx is not only its neuromodulation mechanism and technology, but its potential to expand how neuromodulation care is delivered.

Historically, brain stimulation treatments for depression have been constrained by clinic-based infrastructure. For example, treatments such as TMS often require frequent in-person visits over several weeks, which can be difficult for individuals balancing transportation needs, work schedules, financial constraints, or caregiving responsibilities.5,6,8 These real-world constraints can delay treatment initiation and contribute to inequities in access to evidence-based care.8

By contrast, an FDA-approved neuromodulation option designed for home use under physician direction introduces a new care delivery pathway for depression, one that may complement existing in-clinic interventions.9 In theory, home-based neuromodulation could reduce treatment burden, improve scalability, and expand access for individuals who may not otherwise be able to receive neuromodulation in a timely manner.

As with any emerging treatment, the broader impact of Proliv™Rx will likely depend not only on clinical efficacy, but also on its integration into real-world care. Key implementation considerations include:

  • Adherence: How consistently can patients complete sessions over time at home?
  • Support and monitoring: What level of clinician follow-up best supports safe and effective use?
  • Coverage and access: How reimbursement models, including health insurance coverage and patient out-of-pocket costs, will support or limit broad adoption and equitable access.

Importantly, these questions reflect an opportunity rather than a limitation. While home-based neuromodulation has the potential to reduce logistical barriers associated with clinic-based care, its real-world impact will depend on how coverage policies evolve and whether reimbursement structures make these treatments accessible to patients beyond those who can afford to pay out of pocket.6 As home-based neuromodulation continues to mature, practical factors such as usability, monitoring, and reimbursement will be central to determining how widely and effectively these approaches can be implemented.

Where might Proliv™Rx fit in the depression treatment landscape?

The FDA indication for Proliv™Rx specifies use as an adjunctive therapy for adults with MDD who did not achieve satisfactory improvement after at least one antidepressant medication.9 This is a meaningful distinction in today’s treatment landscape, particularly because many interventional or neuromodulation therapies are often positioned later in care pathways, after multiple medication trials.7 

From a practical standpoint, Proliv™Rx may help fill an important gap: offering a regulated, physician-directed neuromodulation option that could be introduced earlier for appropriate patients, without requiring the same degree of clinic attendance as other stimulation-based approaches. If adopted thoughtfully, this model could support more flexible, patient-centered care, especially for individuals whose depression symptoms make it difficult to sustain frequent in-person treatment schedules.

Looking ahead, Proliv™Rx also represents a broader shift in how depression treatments may evolve: toward care models that combine clinical oversight with more accessible delivery, allowing evidence-based neuromodulation to reach patients in ways that better fit real life.

As clinicians and health systems gain experience with Proliv™Rx, additional research and real-world data will be valuable for clarifying which patient subgroups benefit most, the durability of symptom improvements, how eCOT-AS integrates alongside medication management and psychotherapy, and whether home-based neuromodulation can reduce delays to care and meaningfully expand access.

Conclusion

Proliv™Rx’s PMA approval represents an important milestone in depression treatment and neuromodulation therapeutics. By introducing a physician-directed at-home neuromodulation option, this approval has the potential to broaden access for individuals who might otherwise face delays or barriers to receiving brain stimulation therapies.9,10

Ultimately, what makes Proliv™Rx especially noteworthy is the direction it points the field: toward depression treatments that maintain medical oversight while becoming more scalable and flexible for patients. As home-based neuromodulation enters clinical practice, the next chapter will be shaped not only by efficacy, but by real-world implementation. 

References

  1. World Health Organization. Depressive disorder (depression). World Health Organization. https://www.who.int/news-room/fact-sheets/detail/depression
  2. Yan, G., Zhang, Y., Wang, S., Yan, Y., Liu, M., Tian, M., & Tian, W. (2024). Global, regional, and national temporal trend in burden of major depressive disorder from 1990 to 2019: An analysis of the global burden of disease study. Psychiatry Research, 337, 115958. https://doi.org/10.1016/j.psychres.2024.115958
  3. McIntyre, R. S., Alsuwaidan, M., Baune, B. T., Berk, M., Demyttenaere, K., Goldberg, J. F., Gorwood, P., Ho, R., Kasper, S., Kennedy, S. H., Ly-Uson, J., Mansur, R. B., McAllister-Williams, R. H., Murrough, J. W., Nemeroff, C. B., Nierenberg, A. A., Rosenblat, J. D., Sanacora, G., Schatzberg, A. F., Shelton, R., Stahl, S.M., Trivedi, M.H., Vieta, E., Vinberg, M., Williams, N., Young, A.H., Maj, M. (2023). Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry: official journal of the World Psychiatric Association (WPA), 22(3), 394–412. https://doi.org/10.1002/wps.21120
  4. Ruiz, A. C., Haseeb, A., Baumgartner, W., Leung, E., Scaini, G., & Quevedo, J. (2025). New insights into the mechanisms of electroconvulsive therapy in treatment-resistant depression. Frontiers in Psychiatry, 16. https://doi.org/10.3389/fpsyt.2025.1614076
  5. Rowan, K., McAlpine, D. D., & Blewett, L. A. (2013). Access and cost barriers to mental health care, by insurance status, 1999–2010. Health Affairs, 32(10), 1723–1730. https://doi.org/10.1377/hlthaff.2013.0133
  6. Kar, N. (2025). Challenges in managing depression in clinical practice: Result of a global survey. Pharmacoepidemiology, 4(1), 5. https://doi.org/10.3390/pharma4010005
  7. Bastiaens, J., Brown, N., Bermudes, R. A., Juusola, J. L., Bravata, D. M., & Marton, T. F. (2024). Utilization and outcomes of transcranial magnetic stimulation and usual care for MDD in a large group psychiatric practice. BMC Psychiatry, 24(1). https://doi.org/10.1186/s12888-024-05928-4
  8. Goldbloom, D. S., & Gratzer, D. (2019). Barriers to brain stimulation therapies for treatment-resistant depression: Beyond Cost Effectiveness. The Canadian Journal of Psychiatry, 65(3), 193–195. https://doi.org/10.1177/0706743719893584
  9. U.S. Food and Drug Administration. Premarket approval (PMA). accessdata.fda.gov. (2025, December 31). https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?ID=P250010
  10. Center for Devices and Radiological Health. Premarket approval (PMA). U.S. Food and Drug Administration. https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/premarket-approval-pma
  11. Carpenter, L. L., George, M. S., Navarro, N., Deutsch, L., & Leuchter, A. F. (2025). A novel home-based, combined occipital and trigeminal afferent stimulation therapy for major depressive disorder: Efficacy and safety results from a double-blind multicenter randomized sham-controlled study. Brain Stimulation, 18(5), 1695–1704. https://doi.org/10.1016/j.brs.2025.08.022
  12. BrainsWay announces FDA approval of Neurolief’s ProlivTMRx neuromodulation system for major depressive disorder (MDD). BrainsWay. (2026, January 12). https://www.brainsway.com/news_events/brainsway-announces-fda-approval-of-neuroliefs-prolivrx-neuromodulation-system-for-major-depressive-disorder-mdd/
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