KELLIE NEWSOME: The FDA just approved an at-home device for difficult-to-treat depression, and today we talk with the lead investigator on the trial, Linda Carpenter.Welcome to The Carlat Psychiatry Podcast, keeping psychiatry honest since 2003.

CHRIS AIKEN: I'm Chris Aiken, the editor-in-chief of The Carlat Psychiatry Report.

KELLIE NEWSOME: And I'm Kellie Newsome, a psychiatric NP and a dedicated reader of every issue. On January 12th, 2026, the FDA approved the first at-home device for difficult-to-treat depression, ProLivRx. The decision came just a month after another historic approval, the Flow device for general depression. Whether you are a psychiatrist, a PA, or a psych NP, these therapies are going to change how we practice, bringing a third path, neuromodulation, into the office alongside the well-trod paths of psychotherapy and psychopharmacology. But unless you've been working in a TMS clinic, this is probably an unfamiliar path. So let's start with some basics. Neuromodulation is when you change or modulate neuronal activity. We already do this with medications, which is sometimes called chemical neuromodulation, but usually we use the term to mean electrical neuromodulation, which includes ECT, TMS, and even the TENS unit for pain. Those are all noninvasive, meaning there is no surgery or implanted device. But we also have invasive neuromodulation in psychiatry for depression: deep-brain stimulation and vagal nerve stimulation.

CHRIS AIKEN: These new approvals, Flow and ProLivRX, are both electrical neuromodulators, like TMS, transcranial magnetic stimulation; they are noninvasive, but unlike TMS, they can both be done in the home without a technician present. Both are bands that the patient wears around their head, but this is where their similarities end. They operate through different mechanisms in different parts of the brain. Flow is a brand name for transcranial direct current stimulation, also known as tDCS. We know a lot about tDCS already. Patients buy these machines off the internet and use them at home, and around 30 randomized trials tell us that tDCS works in depression. What has been missing, though, is federal approval, and with that, better regulation of these devices. Flow brings us that. It looks like a pair of Bose headphones, with the headphones over the forehead, and that is where it delivers the electricity, to the left frontal lobe, the seat of depression. Flow is FDA-approved for general depression, and even though the FDA allows its use as an adjunct to antidepressants, it is not approved and is not known to work for treatment-resistant cases.

KELLIE NEWSOME: That is where Proli RX stands out. This device is for patients who failed at least one antidepressant medication. In the trial, the average number of failed meds was 1.8. ProLivRx also stimulates a different part of the brain. Instead of stimulating the frontal lobe directly, it aims to alter brain function indirectly by stimulating sensory nerves, the occipital and trigeminal nerves, but before we get too deep into the mechanism, let's talk with Linda Carpenter about when to use it, how to use it, and the pivotal study behind its launch.

CHRIS AIKEN: Hi Linda, thanks for joining us. Oh, and I see you have the ProLiv device in your hand. Tell us how it works. How do people wear it?

LINDA CARPENTER: The Neurolief device sits on your head, and it has sponge electrodes which make contact with branches of the trigeminal nerve, and in the back, it has electrodes that sit through the hair, and they’re making contact with the occipital nerve, which is this nerve that runs up the back of your neck. It focuses the stimulation on the nerve branch, and so the nerve branch conducts the impulses down into the brainstem and up through areas of the brain that regulate depression. The trigeminal nerve goes down to the brainstem to this area called the solitary tract nucleus. And other treatments we use for depression that have a similar mechanism, like vagus nerve stimulation, which is an implanted device, Ihave one of those here. So, the new technology is finding peripheral branches that connect to deep cranial nerves and have pathways to these areas in the brain.

CHRIS AIKEN: Linda, you were involved in the trial that got ProLiv approved. I have it here in the Journal of Brain Stimulation. It just came out, along with Mark George, who did some of the original TMS trials, Morgan Dancy, Lisa Deutsch, and Andrew Leuchter. A couple of things stand out to me about this trial. First, none of the authors work for the company that makes ProLiv. Another is the effect size. It’s a large effect size, around 0.8, which is similar to what we see with IV ketamine, and making the effect size more believable, the blind was intact. Patients were not able to tell if they got the sham stimulation or the real thing. So, how did you make the sham stimulation so believable in this trial?

LINDA CARPENTER: It's not hard to make a good sham with a take-home stimulation device. Because what these devices do, the sham looks and feels the same when the person puts it on, and it actually stimulates at a slightly different frequency that is not the therapeutic frequency. The patient can feel that they’re getting stimulation, so it’s very hard for them to guess whether they have the active or the sham device. We did our study on patients with major depressive disorder as the indication, and our patients had failed to respond to antidepressants, so they were in a pharmacoresistant kind of category, and also they were also on an antidepressant, and this was used as an adjunct to the ProLiv stimulation, which they used at home for eight weeks. For Flow, there weren’t necessarily people who had failed to get better with medications, so it could be a first episode of depression, your first treatment.

CHRIS AIKEN: And I understand the approval was based on this one trial, which is a little unusual for the FDA, which usually requires two trials. But this one was done under breakthrough status because of the novelty of the treatment and the need in treatment-resistant depression. So, tell us about the kinds of patients you enrolled. Which I think was 124 patients.

LINDA CARPENTER: We did our study on patients with major depressive disorder as the indication, and our patients had failed to respond to antidepressants, and would be that pharmacoresistant kind of category; and also they were on an antidepressant that was used as an adjunct to ProLiv stimulation, which they used at home for eight weeks.

CHRIS AIKEN: And this is different from Flow, the tDCS device, which is not approved in treatment-resistant cases.

LINDA CARPENTER: For Flow, they weren't necessarily people who had failed ot get better with medication, so it could be your first episode with depression, your first treatment.

CHRIS AIKEN: And while ProLiv has just this one study, there are many studies behind Flow using other transcranial direct current devices, and some of that research, I understand, you were involved in. And the big picture there, what it looks like to me, is that Flow or tDCS really doesn’t work well in treatment-resistant cases. They have tested it, some of those trials failed. If anything, there’s a small effect size that might come out there. But this is where we go for treatment-resistant cases, and instead, what the approval Flow is bringing us is finally, an approved, reliable device we can use instead of the do-it-yourself, buy the parts off the internet kind of devices that we have seen used at home for tDCS.

LINDA CARPENTER: Exactly. You have exactly described Flow, because as you've pointed out, there have been many trials of tDCS in depression with different sorts of devices, and they have a lovely device and data to go with it. So, not treatment resistant. So, for patients coming into the Neurolief trial, many of them had already tried and sometimes even failed to get better with treatments like TMS. So it certainly could be something that you used earlier on, but your patients are at least already on some antidepressant.

CHRIS AIKEN: Would you consider ProLivRX before TMS?

LINDA CARPENTER: I'd probably try it before TMS, because these are patients, some of whom had already tried TMS. Some of the patients in our study had TMS, and they got better, but then they got sick again, and instead of going back to TMS again, they wanted to try something else. So, that's another group, because it's more convenient to use something at home than to come to a clinic. TMS requires you to be there five days a week for six weeks in a row, sometimes longer. And it's a great treatment, but it's prohibitive for so many patients.

CHRIS AIKEN: Well, one thing that's kept us from using TMS at home is it takes a lot of power, not more power than the average home has. So how does ProLiv get its juice?

LINDA CARPENTER: ProLiv is plugged in and charged with a little USB. You do that right at home, and then it's got its own little internal battery, so it's not a lot of electricity. You're absolutely right that one of the rate-limiting steps for having magnetic stimulation at home is how much energy has to go through a coil and a thyristor to make these like pulsed electrical impulses that will generate a magnetic pulse. So, here we're talking about low-intensity electrical current.

KELLIE NEWSOME: Wait, it’s time for the CME quiz. Earn CME through the link in the show notes.

1. Which population is ProLivRx approved for?

A. Major depression with one more antidepressant failures

B. Major depression after two or more antidepressant failures

C. Major depressive disorder, moderate to severe

D. Major depressive disorder, recurrent

CHRIS AIKEN: So, you take a patient with treatment-resistant depression, what would make you turn to ProLiv instead of say, augmentation with aripiprazole or lithium?

LINDA CARPENTER: You know, Chris, that's an interesting question, and it's such a personalized answer because for some people it's just easy to take a pill every day, and that is a perfect place for them to start. For some people, the side effects associated with our available antidepressants are totally unacceptable. And so they'll start them, and then they can't stand it, and they go off, and then they continue to press, but if it's not working, we have to think about the next step. And when we think about the next options, when medications aren't working, for many years, we've had to just go next med, next med, next med, and people go years for trialing different meds, maybe one of them works or helps them a teeny bit for a month, and then it stops. But now, as we have more of these different types of treatments that have different targets, trying to get into the pathology and the brain. And so now we've got more and more of these to try; and then again, it becomes issues of patient preference, and I hate to say this, but the other thing that will really determine what people pick next is the cost.

CHRIS AIKEN: We don't yet know anything about cost or insurance coverage around ProLiv, but it'll probably be sold as a subscription model. What that means is that patients won't be able to activate it or use it without the app on their cell phone, and the app is going to be controlled by the company. So, the patient is essentially going to need to get refills from their doctor to have regular visits to keep that app activated. And there will probably be a cost, which we hope insurance will cover for the use of the treatment. So I suppose that maintenance will be possible with the treatment; there'll just be an extra cost to reinitiate it, but what do we know about the need for maintenance after an eight-week course?

LINDA CARPENTER: You are right. There are chronic illnesses, depression is like diabetes, and it's rarely gonna be the case, at least the kinds of patients that we treated in this ProLiv trial, there are patients who are going to need maintenance. How soon or how far apart, that's something that our field needs to work out in research in some ways, to determine. I was really delighted to see in the ProLiv study that we set it up so that there was a maintenance schedule, which allowed people to continue to get treatment.

CHRIS AIKEN: Are all of the treatments gonna be done at home, or are we gonna monitor some of them in person?

LINDA CARPENTER: Well, one of the things that we anticipate with this is that the first use or discussion about it will be in and office, or in a telehealth visit where you can make sure that they understand, and try it and have competence with putting it on and fitting it and know how to turn it on, and help them interface with their smartphone. The smartphone is great when it interfaces with the device; it gives you step-by-step instructions, and it's also Bluetoothing to the device, so it's reading and being able to just tell you when things can start and when things can stop. ProLiv has this interface not only with the patient's app on their phone, but it also sends information to the cloud. So the physician in their office can be monitoring adherence, how often the patient's using it, if the impedances are good, you wanna make sure that your impedances are good, so the device is functioning and getting the right amount of current in the right place. And so, the model that we anticipate is that doctor prescribes it and then they continue to monitor the patient either by telehealth or by inpatient visits, periodically, every couple of weeks, every month, whatever the clinical need is. 

CHRIS AIKEN: In the studies, the sessions were done for 40 minutes twice a day, with at least five hours apart between the two sessions, and I noticed there was some flexibility there; it said it was done five to seven days a week. How much flexibility did you actually allow in using this device?

LINDA CARPENTER: I used it twice a day, but they have a little bit of flexibility, whether they were using it a little more at one time than a little bit less than the other.

CHRIS AIKEN: I understand the device has an accelerometer in it to monitor the patient's position, and part of the reason is that they can't use it if they're upside down. Are there any other limitations in what they can do while using it?

LINDA CARPENTER: No, you can eat or move about, because all of these devices involve electricity, we don't want you to go in the shower or take a bath while you've got a device on your head, my recommendation to anybody that's getting brain stimulation is to think about what they choose to do while they're wearing it, because there's some evidence that there are synergistic effects between stimulation and what your brain is doing. Not necessarily with this device. I can't say we did a study of like, what are you doing while you're wearing this? But in the tDCS world, certainly, there are devices and studies where they've evaluated interaction between what you're doing and the stimulation, generating the result. So, my recommendation would be for people to do things that are not highly stressful, do it when they're relaxing, watching television, it wasn't studied as a device, of what you wear when you sleep. So we don't really have data yet to say either, these sorts of things, of what you should do when you're sleeping.

CHRIS AIKEN: So we're aiming for two 40-minute sessions, five hours apart, and is any time of day, okay?

LINDA CARPENTER: Anytime of day is okay, and that's one of the great things, the convenience home, I guess people could use it in work if they have the comfort and privacy of where they work. If they wanna wear it in public as they're walking around in the subway, there's nothing to prohibit that, it's not a sort of a interrupting or distracting experience. It feels quite good, actually. It's got this sensation that you feel on your scalp, sort of like those metal things that they take that go like this, and they kind of send little shivers up and down the back of your neck. 

CHRIS AIKEN: Oh, yes. They are not electronic, but you're talking...

LINDA CARPENTER: Just a scalp massager.

CHRIS AIKEN: Scalp massagers for $10. They're like little wires.

LINDA CARPENTER: Yes, well, when you put this on it, at first, you do get a little bit of that sort of sensation in your scalp, and it makes a little bit of an Ooh, feeling down the back of your neck, and it's quite nice. So it's a relaxing feeling, and it's not a distracting experience. So that you would say, “Oh, I can't read while I'm wearing this”, you certainly could read or be on your computer.

CHRIS AIKEN: Are there any side effects to ProLiv, or things that patients did not like about the treatment?

LINDA CARPENTER: Yeah, one of the things that we experienced is that people need to learn how to set up the device with the right size so it fits on their head comfortably, right? So it has to make contact in the back and contact in the front, and it's adjustable, and you wanna get it not too tight, so you like feel like there's something constricting your head, because that can be annoying, if something feels like it's a tight band around your head, you want it just tight enough so that it's touching and not too tight. The other thing with this device is that patients titrate the level of intensity themselves. We encourage them to go up until it feels uncomfortable and then back down, so it's comfortable. And there's always somebody who thinks more is better to go higher and higher. And you don't want it to be uncomfortable. That's not good. You shouldn't push it to the point where you're feeling stimulation that gives you a headache. And that would be a risk that you could have a headache. If you didn't properly moisten these little sponges inside, then, and if it's against your skin and the electricity is trying to get in, it could make redness or even kind of a burning sensation. But I think burning's a little bit extreme. But you could get like a redness or an irritation. So again, that's all part of the training to use the device and make sure that somebody, you can see them walk through the steps, they know how to put it on, how to be comfortable, how to not turn it up too high. It'll time out, so it won't let you use it for too long in each session. But those are the main side effects, basically the contact, whether you get a headache, if you've got it too tight, or you don't have the good context, and you get some irritation on the skin. Other than that, we don't have any evidence of interactions with medications.

CHRIS AIKEN: Thank you, Dr. Carpenter.

KELLIE NEWSOME: Join us next week for more ProLivRX as we continue this interview with Linda Carpenter. Dr. Carpenter is a professor of psychiatry at the Alpert Medical School of Brown University and chief of the Mood Disorders Program at Butler Hospital. She has conducted NIH and industry-sponsored trials on vagus nerve stimulation, deep brain stimulation, TMS, tDCS, and esketamine. Do you have topics you'd like us to cover? Send your feedback and questions on all things psychiatric to asktheeditor@thecarlatreport.com. Visit thecarlatreport.com, but we have a special offer for our podcast listeners: you can get $30 off your first-year subscription to the journal with promo code PODCAST.