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How Proliv™Rx Works

Proliv™Rx is an FDA-approved, prescription, physician-directed therapy delivered at home for patients who haven’t adequately responded to antidepressants.
Physicians direct care while patients complete a guided program with ongoing progress tracking.

How Proliv™Rx fits into clinical workflow

Integrates into behavioral health and primary care pathways with minimal disruption

Proliv™Rx adds a next-step therapeutic option without changing existing clinical routines.
Physicians evaluate patients and prescribe Proliv™Rx as they normally would, while Neurolief manages all operational and logistical components.

This allows Physicians to maintain their regular care cadence while patients complete a structured home-based therapy program.

Structured home-based
therapy program

Secondary title
1
Prescription
By clinician
1

The clinician identifies a patient who has not adequately responded to antidepressants and prescribes Proliv™Rx.

2
Fulfillment
& onboarding
By Neurolief
2

Neurolief manages all logistics, including:

  • Proliv™Rx & pads shipment
  • Proliv™Rx activation
  • Training on proper Proliv™Rx placement
  • App set up and use
  • Safety orientation

Clinics do not handle Proliv™Rx distribution or technical support.

3
At-home therapy
By patient + app
3

Patients complete two daily therapy sessions over 8 weeks within a prescribed program.
The Proliv™Rx app provides:

  • Placement verification
  • Step-by-step session guidance
  • Automated adherence reminders
  • Safety prompts
  • In-app PHQ-9 assessments

Neurolief actively supports patients throughout the program.

4
Clinical oversight
By clinician
4

Physicians stay in control, they decide when to check on their patients and can view progress remotely. There’s no need for extra visits or staff time unless the doctor feels it’s necessary

5
Program completion
By Neurolief
& clinician
5

Upon completion of the therapy program, the clinician evaluates treatment outcomes and determines whether to:

  • Continue to another Proliv™Rx therapy cycle
  • Transition care
  • Conclude and return Proliv™Rx

Neurolief manages Proliv™Rx retrieval or continuation logistics.

The therapeutic mechanism behind Proliv™Rx

Clinically established brain neuromodulation, optimized for effectiveness and access

Neuromodulation is a clinically established next-step treatment for patients who do not respond adequately to antidepressants.
Proliv™Rx builds on this foundation by applying proven neuromodulation principles in a way that is effective at the brain networks level and accessible earlier in the care pathway through structured, at-home treatment under clinical oversight.

The Proliv™Rx Neurorouter

Where Engineering Meets Neural Precision

Advanced Multi-Channel Targeted Neuromodulation

  • Proprietary architecture integrating six electrodes and three adaptive stimulation channels, dynamically modulating output in real time to deliver optimized neuromodulation throughout the treatment session.
  • Targeted afferent stimulation with anatomical precision, positioning each electrode directly over its designated nerve pathway to ensure focused and reproducible activation.
  • Distinct capability to non-invasively stimulate the greater occipital nerve branches, effectively overcoming the hair barrier to enable consistent nerve engagement.
  • Miniaturized, high-efficiency electronics engineered for high-performance output, delivering powerful stimulation safely and comfortably to enhance therapeutic effectiveness and clinical outcomes.
  • Proprietary specially designed Portpads that facilitate sufficient electrical conduction

Engaging Core Brain Regions Associated with Depression

Advanced Multi-Channel Targeted Neuromodulation

Proliv™Rx employs a multi-channel, focal afferent stimulation architecture designed to engage depression-regulating neural networks.

 

  1. Three independent output channels deliver proprietary patterned stimulation across six electrodes1,2
  2. Concurrent activation of trigeminal (frontal) and occipital (posterior) nerve pathways1,2
  3. The afferent inputs converge at the trigemino-cervical complex (TCC), a recognized brainstem relay hub1,2
  4. Signals project to additional brainstem nuclei involved in autonomic regulation, arousal, and neurotransmitter modulation, and to higher cortical and subcortical regions associated with depression1,2,3,4

By combining multi-channel delivery with focal neural targeting, Proliv™Rx engages multiple interconnected neural pathways through a bottom-up neuromodulatory mechanism, which influence brain networks associated with depressive symptomatology.

References
  • 1 Oved D, Sharon R, Tepper SJ. A device review of Relivion®: an external combined occipital and trigeminal neurostimulation (eCOT-NS) system for self-administered treatment of migraine and major depressive disorder. Expert Review of Medical Devices. 2021;18:333–342..
  • 2 Carpenter LL, George MS, Navarro N, Deutsch L, Leuchter AF. 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. 2025;18(5):1695–1704.
  • 3 Kovacs, S. et al. Central Effects of Occipital Nerve Electrical Stimulation Studied by Functional Magnetic Resonance Imaging. Neuromodulation Technol. Neural Interface 14, 46–57 (2011).
  • 4 Cook, I. A., Espinoza, R. & Leuchter, A. F. Neuromodulation for Depression. Neurosurg. Clin. N. Am. 25, 103–116 (2014)

Precision neuromodulation through key nerve pathways

Trigeminal Nerve Stimulation (TNS)

Influences depression-related regions via afferents to the nucleus tractus solitarius (NTS), regulating autonomic and stress responses, and through connections with the LC, reticular activating system (RAS), and raphe nuclei (RN), the primary serotonergic source.1,2

References
  • 1 Adair D, Truong D, Esmaeilpour Z, Gebodh N, Borges H, Ho L, et al. Electrical stimulation of cranial nerves in cognition and disease. Brain Stimul 2020;13:717-50.
  • 2 Cook IA, Espinoza R, Leuchter AF. Neuromodulation for depression: invasive and noninvasive (deep brain stimulation, transcranial magnetic stimulation, trigeminal nerve stimulation). Neurosurg Clin N Am 2014;25:103-16
  • 3 Matharu MS. Central neuromodulation in chronic migraine patients with suboccipital stimulators: A PET study. Brain 2004;127:220–30.
  • 4 Aston-Jones G, Shipley MT, Chouvet G, Ennis M, van Bockstaele E, Pieribone V, et al. Afferent regulation of locus coeruleus neurons: Anatomy, physiology and pharmacology. Prog Brain Res 1991;88:47-75
  • Placebo:
    Explained
Occipital nerve stimulation (ONS)

Enhances cerebral blood flow in the dorsal rostral pons,3 which houses the locus coeruleus (LC)- the brain’s main source of norepinephrine, regulating arousal, attention, and stress, all disrupted in depression.3,4 Also affects the anterior cingulate cortex (ACC) – critical for processing negative emotions and cognitive control of affective responses.3

References
  • 1 Adair D, Truong D, Esmaeilpour Z, Gebodh N, Borges H, Ho L, et al. Electrical stimulation of cranial nerves in cognition and disease. Brain Stimul 2020;13:717-50.
  • 2 Cook IA, Espinoza R, Leuchter AF. Neuromodulation for depression: invasive and noninvasive (deep brain stimulation, transcranial magnetic stimulation, trigeminal nerve stimulation). Neurosurg Clin N Am 2014;25:103-16
  • 3 Matharu MS. Central neuromodulation in chronic migraine patients with suboccipital stimulators: A PET study. Brain 2004;127:220–30.
  • 4 Aston-Jones G, Shipley MT, Chouvet G, Ennis M, van Bockstaele E, Pieribone V, et al. Afferent regulation of locus coeruleus neurons: Anatomy, physiology and pharmacology. Prog Brain Res 1991;88:47-75
  • Placebo:
    Explained

In Proliv™Rx clinical study, 87% improved by one or more depression severity levels and 31.7% of these difficult to treat patients reached full remission

See Clinical Evidence

Keeping physician informed throughout the program

Physician maintain visibility into treatment progress through structured reports generated during the program. Reports can be shared during visits or via secure messaging.

Throughout the 8-week program, patients can generate a detailed progress report from the Proliv™Rx app. The report summarizes key treatment metrics and provides physician with a clear snapshot of adherence to the therapy and progress

Each report includes:

  • Session completion & adherence – total sessions completed, missed sessions, and adherence rate
  • Standardized symptom tracking – PHQ-9 scores at baseline and every two weeks throughout the course of treatment.
  • Intensity levels & adjustments – automatic and patient-adjusted stimulation levels
  • Program outcome – patient progress and overall program summary
  • Program completion status – confirmation that the full treatment course was completed
Download sample report

A guided, structured experience patients complete at home

The app guides patients through physician-prescribed therapy sessions within a defined treatment program.
Onboarding & placement validation
The Neurolief Customer Care team and app guide the patient through device setup, and placement verification before beginning therapy.
Guided daily sessions
Guided 40-minute treatments, with contacts quality check, automatic intensity adjustment and optional manual fine-tuning for patient comfort.
Reminders & adherence support
Automated reminders help maintain consistency. Neurolief provides follow-up outreach when sessions are missed, reducing the need for clinic involvement.
PHQ-9 Tracking
Patients complete scheduled PHQ-9 assessments in the app; results are available for physician oversight during routine follow-up.
See Patient Webpage

Have questions or want more clinical details?

Our team can walk you through the clinical evidence, workflow fit, coverage pathways, and implementation options for your system.
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