FDA-Approved Breakthrough! Neurolief Brings ProLivᵀᴹ Rx to the World!
And I define acronyms in one place to make you sound smart at parties.
I am so excited, readers. The other night had a great turnout—and a vibe—at RAMHT-AI 2026. We had excting anouncements, myriad. Here are just two:
Josh Stevens, CEO of Beckley Clinical previewed 4 payors enganged and interested in covering their deployment of Ketamine-Assisted Therapy—and substantial funding raised! They are getting a referrals directly from hospitals, underscoring the severity of the need for potent therapies. I’m a personal fan of Josh, for full disclosure. It’s a bit of a bromance.
Jonathan Javitt, M.D., MPH, CEO of NRx let the world that not only is KetaFree submitted to the FDA to be approved as an on-label ketamine treatment, but they have other neuroplastinogens in development, and have partnered with with Neurocare to bring neuroplastic therapies for bipolar and unipolar depression to scale.
I had an announcement, also! At long last, at Neurolief, where I am CMO, we have an at-home treatment for difficult-to-treat depression! Here is the the label:
The Proliv™Rx System provides focal external Combined Occipital and Trigeminal Afferent Stimulation (eCOT-AS) treatment. It is intended as an adjunctive treatment for Major Depressive Disorder (MDD) in adults who failed to achieve satisfactory improvement from at least one previous antidepressant medication, for use at home or in clinic. It is a prescription-only device.
People are used to hearing about FDA cleared with devices in psychiatry, because the one we familiar with is transcranial magnetic stimulation. This is FDA-approved. That's different than clearance.
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
The data is worth reading. However, instead of writing about what kind of a product Proliv Rx is…I’m going to make myself useful. I’m going to define terms—because it’s getting really confusing. Neuromodulation is getting to be as bad as therapies. eCOT-AS, tDCS, DBS, ECT, TMS, nVNS, tFUS, VNS, dTMS, rTMS, eTNS, fTUB.
I just made up fTUB. You probably didn’t even notice!
I'll start with eCOT-AS, because that's what ProLivᵀᴹ Rx is—but as a bonus, I will do the the other acronyms too.
eCOT-AS: External Combined Occipital and Trigeminal Afferent nerve Stimulation.
This technology allows the use of electricity to gently stimulate sensory nerves on your head. One of the quirks of the sensory nerves that allow you to feel anything on your head? It is that not all of them are cranial nerves! Your forehead and face are innervated by the trigeminal nerve for sensory input into the brain. But the back of your head? That's actually a sensory nerve that sneaks up from where the spinal cord exits around your shoulders through what we call the brachial plexus, and then travels back up to be the sensory nerves (so you can feel anything on the back of your head), which, in anatomy lab, is called the occiput. Thus, occipital nerves are really spinal nerves that took a U-turn.
So, this device stimulates the sensory nerves on the front of your head, using two separate divisions of the trigeminal nerve, and the back of your head, which gets into your brain via a spinal sensory nerve. If that sounds like a lot of sensory nerve bandwidth, that's because it is. This allows delicately pulsed electrical energy to re-synchronize deep brain circuits in a way that's really efficient when it comes to the amount of electricity needed, which means the whole thing runs a rechargeable battery in the device. It “tickles” your nerves, and the pattern of tickling can reset depression. Neurolief did this once before with a product called Relivion MG, for migraine.
tDCS: Transcutaneous Direct Current Stimulation
Batteries have an anode and a cathode. Current flows from the anode to the cathode. tDCS uses direct current, goes through your skin (“transcutaneous”) and into your brain.. Then, if you're the Flow neuroscience device, you delivers a direct current stimulation to your brain, which, according to the FDA can help with depression, as long as it hasn't demonstrated itself to be hard to treat.
The mechanism difference between eCOT-AS and tDCS? eCOT-AS stimulates sensory nerves to change the brain. tDCS directly stimulates the brain to change it.
DBS: Deep Brain Stimulation.
Deep brain stimulation involves a neurosurgeon implanting, a long, thin stimulator deep in the brain (usually bilaterally), and then a battery pack and digital brain for that simulator somewhere in your chest, and then connecting wires to those leads. This allows us to put brain stimulation deep in the brain, and that's necessary for some conditions like Parkinson's disease, and maybe necessary for OCD, essential tremor, and dystonia, as well as other conditions in the future, like depression. But it's Neurosurgery. Most of these neurosurgical procedures use patterned pulses of stimulation to regulate a neural circuit of interest. In OCD, it's used to turn down the function of the brain circuit that keeps you worrying when left to its own devices.
ECT: ElectroConvulsive Therapy
This procedure uses electricity between an anode and a cathode at a relatively high dose to induce a seizure. This is done under anesthesia, so the body lays still, but the brain is having a generalized seizure. It turns out that seizure is a way to treat psychiatric disorders, and it's also a treatment for epilepsy that you can't control with medicines safely. When we induce seizures, we make them less likely to happen on their own. So we often use ECT in pregnancy to protect women and their in utero almost babies from the exposure to antiepileptic drugs.
It's the seizure that's therapeutic, but you're under anesthesia when you get this treatment. It requires a doctor, anesthesiology, and a PACU, and is dramatically under utilized in current psychiatric practice, despite decades of demonstrated efficacy.
More details on ECT as a depression treatment are available here.
TMS/rTMS: Transcranial Magentic Stimulation
TMS is a procedure that uses an electromagnet to induce electrical fields in nearby wires. In your brain, instead of doing it in literal wires, it induces firing in neurons, which have long axons, which are functionally wires. The r in rTMS is repetitive, which is barely relevant any more, but the origional TMS devices were fired only once to stimulate the brain once, as a measurement tool in neurophysiology labs.
A nice summary of side effects of TMS is available here.
VNS: Vagus Nerve Stimulation
This is also Neurosurgery. Instead of implanting, a stimulator in the brain itself, a stimulator is implanted in the vagus nerve, the cranial nerve that goes from the brain to the body and controls the “rest and digestive” (parasympathetic) nervous system, as well as a bunch of other things on the way down. The Vagus nerve is really one of the top 12 cranial nerves. It may be even among the top 12 nerves in the body. It's a leading nerve. There is evidence to support it's used in epilepsy, depression, and clinical trials going on right now in bipolar depression.
It's got one of those battery packs, that you have planted into the chest, just like DBS, but there's no drilling into your skull part of the procedure. I’ve written about it’s use in Rheumatoid arthritis before.
nVNS: Non-invasive Vagus Nerve Stimulation
We learned about the vagus nerve above! This is non-surgical peripheral (on the neck) vagus nerve stimulation. There are a number of non-prescription version of this approach, but the only prescription one I know if is the GammaCore device, FDA-labeled for Migraine, Hemicrania Continua, and Cluster Headache and is going through an FDA breakthrough process for PTSD. I wrote about that data here.
I’ve published on a novel use of nVNS in very hard to treat depression here.
dTMS: deep Transcranial Magnetic Stimulation
This is repetitive TMS (rTMS) with a patented H-coil, and the choice of the word “deep” may or may not be a marketing decison.
Regardless, it’s a variety of coil geometries for inducing magnetic fields in the brain.
eTNS: external Trigeminal Nerve Stimulation
This is like eCOT-AS, but just eT-AS. The brand name is the Monarch eTNS device, and it is an FDA-cleared breakthrough device for refractory seizures, and ADHD in youth.
I’ve written about this a lot. I’m looking forward to new data on large scale replication trials that should be published soon.
A friendly reminder— the search function on this newsletter is your friend. I’ve written over 1000 articles and podcasts to date, so if you want to know what Owen Muir or his co-authors think, search for it! I have probably written something about most things you could search for.
ADHD
Thanks for reminding us about the search function! I’m now going to search everything you’ve written on treating migraines!