Proliv®Rx

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Proliv®Rx, developed by Neurolief, is an FDA-approved, prescription brain stimulation therapy intended as an adjunctive treatment for adults with major depressive disorder (MDD) who have not achieved satisfactory improvement from at least one previous antidepressant medication. 

The therapy is delivered through a structured, physician-supervised, at-home program and is designed to expand access to clinically validated care for patients who might otherwise forgo advanced treatment due to geographic, logistical, or treatment burden barriers. 

The technology builds on Neurolief’s broader neuromodulation expertise, first commercialized in migraine.

For many patients with depression, the issue is not a lack of treatment options, but limited access to effective care when antidepressants fall short. After an inadequate response, patients are often prescribed additional medications, including augmentation with antipsychotics—approaches that may offer limited benefit while increasing the risk of side effects, such as weight gain, elevated blood sugar, higher cholesterol and triglyceride levels, and more.

Advanced therapies such as electroconvulsive therapy (ECT), Esketamine and transcranial magnetic stimulation (TMS) require frequent visits to specialized centers, sometimes daily for multiple weeks. For patients in rural or underserved areas, this may mean traveling long distances, including several hours each way, to receive interventional care. 

Barriers to care also include the persistent stigma surrounding mental health. Many patients delay or avoid seeking treatment due to concerns about being seen in a clinical setting or the burden of repeated in-person visits. As a result, they may remain in prolonged cycles of medication adjustments without achieving meaningful relief.

Receiving therapy at home addresses these challenges by supporting privacy and dignity while maintaining physician oversight. For a condition where delays in treatment can have serious consequences, including worsening symptoms and increased risk of self-harm, access to advanced care may be lifesaving. 

ProlivRx is based on External Combined Occipital and Trigeminal Afferent Stimulation (eCOT-AS), also referred to as XCOT3. This first-of-its-kind, non-invasive medical technology simultaneously stimulates both the occipital and trigeminal nerve pathways, enabling coordinated neuromodulation of brainstem and higher-order networks associated with depression.

Using three independent stimulation channels and six electrodes, ProlivRx delivers sequential, anatomically targeted stimulation to the trigeminal and occipital nerve branches across the forehead and back of the head. These afferent signals are designed to converge at the trigeminocervical complex in the brainstem and engage broader neural networks involved in mood regulation. ProlivRx is engineered to provide focal stimulation rather than diffuse current delivery. 

More simply, ProlivRx works through the brain’s own neural pathways, using focused stimulation through specific nerves rather than sending broad electrical current across the head. 

For patients, the goal is a treatment that is more precise, consistent and practical to live with—one that can be done at home under a doctor’s care without the time, travel and disruption often associated with clinic-based treatments. Just as importantly, ProlivRx is built to support real-world, everyday use. The treatment is gentle and may cause a tickling or tingling sensation on the head.  

 ProlivRx is supported by the MOOD pivotal study, a randomized, double-blind, sham-controlled, multicenter trial in 124 adults with MDD who had not responded adequately to antidepressant medication. Results were published in the peer-reviewed journal Brain Stimulation.

Key findings from the MOOD study include:

• At 8 weeks, active treatment produced significantly greater improvement in depressive symptoms than sham, with an adjusted mean HDRS17 improvement of 8.62 points versus 6.01 points.
• Remission rates at 8 weeks were 21.3% with active treatment versus 6.0% with sham.
• After 16 weeks of active treatment, 31.7% of patients achieved remission and 70.7% achieved clinically substantial improvement.
• 81% of patients had severe or very severe depression at baseline, compared to only 15% after 16 weeks of active treatment. 
• No patients had mild or no depression at baseline, compared to 56% after 16 weeks of active treatment.
• Treatment was generally well tolerated, with adverse events that were mostly mild and transient, and 96% compliance with the daily treatment regimen. 

Unlike TMS, which uses a large magnetic coil in a clinic to send stimulation through the skull to targeted areas in the brain, ProlivRx works through nerve pathways around the head. Using three independent channels, it stimulates six nerve branches—four in the forehead and two at the back of the head—to send signals toward brain areas involved in mood regulation. It is designed to work through the body’s own nerve network rather than trying to stimulate the brain directly through the skull. 

ProlivRx also differs fundamentally from cranial electrotherapy stimulation (CES) and transcranial direct current stimulation (tDCS), which are lower-intensity modalities that typically use a single channel to send low-level current broadly across the head and through the skull. In contrast, ProlivRx uses a multi-channel, targeted approach to engage specific nerve pathways around the head while minimizing direct cortical stimulation. Importantly, ProlivRx is a prescription-only therapy for adults with major depressive disorder, designed for at-home use under physician supervision and supported by remote monitoring.