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How a new FDA approved device for difficult-to-treat depression engages the brain through the sensory nerves in part II of our interview with Linda Carpenter.
Publication Date: 01/26/2026
Duration: 12 minutes, 33 seconds
Transcript:
CHRIS AIKEN: Sensory deprivation. It sounds peaceful, relaxing at first, but it can get pretty depressing when there's no input heading into the brain, and today, we'll find out what that means for the new FDA-approved ProLivRx.
KELLIE NEWSOME: 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. That's the sound of a pottery wheel, and it's just a taste of what you'd be feeling if your hands were coaxing the cool, soft clay as it spins in front of you. But this study from 2017 will give us a better sense. It took place in Hong Kong. Researchers randomized 106 patients with depression to a course in clay art, pottery making, or a similar course in visual art. After three weeks, those who worked the clay with their hands saw improvements in depression. The visual art group, not so much. So what made the difference? One possibility is the senses. Think about touch. Maybe you recall a story from your training about the harrowing way that doctors and nurses discovered the power of touch? It was during World War II. Infants who had lost their parents in the war were placed in orphanages. This was the antibiotic era, so the first thing on people's minds was cleanliness, how to keep these babies free of infections. The goal was achieved, but it came at a cost. Deprived of touch, the children failed to thrive. They regressed in their development, withdrew, as if depressed, in what psychoanalyst René Spitz called anaclitic depression. We learned the lesson, and that's why we go out of our way to keep babies stimulated today with touch and even massage. We decorate their rooms with spinning objects and musical toys of every texture. One company even took it a step too far, advertising Baby Einstein videos that would deliver all this sensory input through a TV show. Research wasn't so kind to Baby Einstein. Passivelywatching videos, no matter how engaging, did not improve development. If anything, it might have slowed language development.
CHRIS AIKEN: Baby Einstein may be a bust, but there are plenty of ways that adults can touch grass that improve mental health. I mean, touch grass literally, and not the cannabis type. Studies suggest that walking barefoot on the grass improves mental health more than walking in shoes, and likewise, walking on rugged terrain may also be better for the brain than walking on flat asphalt surface. Think of all that rich sensory information at play between the brain and the foot. Turning to clinical trials, we find that acupuncture, massage, gardening, aromatherapy, and music therapy all improve depression in randomized controlled trials compared to reasonable controls, particularly acupuncture, which has support from over 64 trials in depression.
KELLIE NEWSOME: On the other hand, sensory deprivation is as depressing in adults as it is in children. We see nearly double the rate of depression in people with sensory impairments like loss of hearing or vision. And while a lot of that is due to the social isolation it causes, the loss of sensory input itself is partly to blame. Take anosmia, the inability to smell. You can still socialize without a sense of smell, yet this sensory loss is associated with thesame risk of depression as hearing loss, a twofold increase. People who have lost their sense of smell feel disconnected, as if living behind glass. The source of smell, the olfactory bulb, connects to the memory center, the hippocampus, and that connection adds a richer layer to our memories, deepening our sense of purpose, much as a good soundtrack enhances a movie.
CHRIS AIKEN: That brings us to ProLivRx, the new FDA-approved neuromodulation device for difficult-to-treat depression. ProLivRx is a band that people wear around their head for 40 minutes, twice a day. And the big news here is that it got approved by the FDA, not just cleared by the FDA, which means it passed a bigger evidence bar than FDA clearance. Before ProLivRx, the other recent approval was the Flow device. All of the devices we use in psychiatry were just cleared. TMS was cleared. ECT just cleared. We don't know how ProLivRx works, but we do know how it operates, by stimulating the sensory nerves, the occipital and trigeminal nerves. Think of it as an electrical massage of the face and head. The trigeminal nerve is the sensory nerve for the face, and the occipital nerve runs down the neck, encoding sensation for the back of the head, the top of the head, and around the ears. Our best guess of how ProLivRx works is that stimulating these sensory nerves has downstream effects in the brain, enhancing blood flow and reorganizing neurotransmitters and synaptic connections in parts of the brain that keep us alert and awake, the reticular activating system, and that regulate actions and emotions, like the locus coeruleus, the cingulate cortex, and that deep well of serotonin in the brain, the raphe nuclei.
KELLIE NEWSOME: Let's hear more in our interview with Linda Carpenter. But first, a preview of the CME quiz. Earn CME through the link in the show notes.
KELLIE NEWSOME: 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. That's the sound of a pottery wheel, and it's just a taste of what you'd be feeling if your hands were coaxing the cool, soft clay as it spins in front of you. But this study from 2017 will give us a better sense. It took place in Hong Kong. Researchers randomized 106 patients with depression to a course in clay art, pottery making, or a similar course in visual art. After three weeks, those who worked the clay with their hands saw improvements in depression. The visual art group, not so much. So what made the difference? One possibility is the senses. Think about touch. Maybe you recall a story from your training about the harrowing way that doctors and nurses discovered the power of touch? It was during World War II. Infants who had lost their parents in the war were placed in orphanages. This was the antibiotic era, so the first thing on people's minds was cleanliness, how to keep these babies free of infections. The goal was achieved, but it came at a cost. Deprived of touch, the children failed to thrive. They regressed in their development, withdrew, as if depressed, in what psychoanalyst René Spitz called anaclitic depression. We learned the lesson, and that's why we go out of our way to keep babies stimulated today with touch and even massage. We decorate their rooms with spinning objects and musical toys of every texture. One company even took it a step too far, advertising Baby Einstein videos that would deliver all this sensory input through a TV show. Research wasn't so kind to Baby Einstein. Passivelywatching videos, no matter how engaging, did not improve development. If anything, it might have slowed language development.
CHRIS AIKEN: Baby Einstein may be a bust, but there are plenty of ways that adults can touch grass that improve mental health. I mean, touch grass literally, and not the cannabis type. Studies suggest that walking barefoot on the grass improves mental health more than walking in shoes, and likewise, walking on rugged terrain may also be better for the brain than walking on flat asphalt surface. Think of all that rich sensory information at play between the brain and the foot. Turning to clinical trials, we find that acupuncture, massage, gardening, aromatherapy, and music therapy all improve depression in randomized controlled trials compared to reasonable controls, particularly acupuncture, which has support from over 64 trials in depression.
KELLIE NEWSOME: On the other hand, sensory deprivation is as depressing in adults as it is in children. We see nearly double the rate of depression in people with sensory impairments like loss of hearing or vision. And while a lot of that is due to the social isolation it causes, the loss of sensory input itself is partly to blame. Take anosmia, the inability to smell. You can still socialize without a sense of smell, yet this sensory loss is associated with thesame risk of depression as hearing loss, a twofold increase. People who have lost their sense of smell feel disconnected, as if living behind glass. The source of smell, the olfactory bulb, connects to the memory center, the hippocampus, and that connection adds a richer layer to our memories, deepening our sense of purpose, much as a good soundtrack enhances a movie.
CHRIS AIKEN: That brings us to ProLivRx, the new FDA-approved neuromodulation device for difficult-to-treat depression. ProLivRx is a band that people wear around their head for 40 minutes, twice a day. And the big news here is that it got approved by the FDA, not just cleared by the FDA, which means it passed a bigger evidence bar than FDA clearance. Before ProLivRx, the other recent approval was the Flow device. All of the devices we use in psychiatry were just cleared. TMS was cleared. ECT just cleared. We don't know how ProLivRx works, but we do know how it operates, by stimulating the sensory nerves, the occipital and trigeminal nerves. Think of it as an electrical massage of the face and head. The trigeminal nerve is the sensory nerve for the face, and the occipital nerve runs down the neck, encoding sensation for the back of the head, the top of the head, and around the ears. Our best guess of how ProLivRx works is that stimulating these sensory nerves has downstream effects in the brain, enhancing blood flow and reorganizing neurotransmitters and synaptic connections in parts of the brain that keep us alert and awake, the reticular activating system, and that regulate actions and emotions, like the locus coeruleus, the cingulate cortex, and that deep well of serotonin in the brain, the raphe nuclei.
KELLIE NEWSOME: Let's hear more in our interview with Linda Carpenter. But first, a preview of the CME quiz. Earn CME through the link in the show notes.
1. Which nerves are directly stimulated by ProLivRx?
A. The cingulate cortex and the brainstem
B. The raphe nuclei and the orbital nerves
C. The orbital and trigeminal nerves
D. The occipital and trigeminal nerves
CHRIS AIKEN: So ProLiv and TMS are both neurostimulation devices. ProLiv, I understand, is stimulating the cranial nerves and getting into the brain indirectly, and TMS is directly stimulating the cortex. Tell us more about how these two devices differ in their mechanisms.
LINDA CARPENTER: We really don't know how any antidepressant pill or stimulation ultimately changes the brain, but we do know a lot of things they do to the brain, and we can infer from them. So TMS, magnetic energy pulses through the scalp and the skull and all the tissues unimpeded, and then on the surface of the brain, called the cortex, an area of neurons is activated. It actually induces current in your brain. So you can induce this current, and you've got them activated and firing, and then they're in networks, and we know that connections between these networks are abnormal in people with depression/anxiety, they're either hyper-connected or they're under-connected; and this area is supposed to be telling the amygdala, “Be quiet. I don't wanna hear the anxiety right now because the house is not on fire, but it's not working”, and those signals are coming through. We think that it's attacking these networks like that.
CHRIS AIKEN: And how does ProLiv’s mechanism compare to Flow, the tDCS?
LINDA CARPENTER: Flow is what we call transcranial direct current stimulation. Now, the difference with Flow is that its mechanism is to shunt current from one area of the brain to another. The mechanisms for something like tDCS, or even for external combined occipital-trigeminal stimulation, and vagus nerve stimulation are much less worked out. But what we know from vagus nerve stimulation helps us understand how we believe the ProLiv, the Neuroleif product, works, and that is that these signals go through peripheral nerves to the brainstem, and have a regulating influence from the bottom up, in the solitary tract nucleus. There's kind of a highway in the brainstem to a lot of areas that regulate mood and anxiety disorders. You can get into the dorsal raphe, where there are serotonin neurons. You can get to norepinephrine neurons and a lot of other areas.
CHRIS AIKEN: Thank you, Dr. Carpenter. We talked today about the theory behind ProLivRx, but its actual discovery was more happenstance. The device was originally developed to treat migraines, and it does. It was FDA-cleared as Relivion in 2021 for migraines. Now, depression and migraines often go together, and while using it for migraines, researchers noticed an unexpected side effect: improvement in mood. With only one study behind ProLivRx, a lot is still unknown about this treatment. The effect size of 0.8 suggests that it makes a meaningful difference, although only 21% of those treated achieved full remission at eight weeks. In Dr. Carpenter's work, that effect did keep building if people used it longer than eight weeks, so there might be people who had delayed effects. But how long do these benefits last? Will it work in bipolar depression? In the clinical trial, it did not cause hypomania or mania, something we can't say for the Flow transcranial direct current stimulation device, as these tDCS machines cause mood switching for about 1 in 30 patients, which is like five times more often than the sham in those studies. ProLivRx also does not burn the skin. That's another risk with Flow, which can cause mild skin burns from the electricity. And ProLivRx does not cause seizures, which is a very rare risk with TMS. It did not impair cognition, and it does not cause insomnia. Although the treatment is a bit time-consuming, it requires an hour and 20 minutes a day. Patients seem to like ProLivRx. They found the mild stimulation relaxing and pleasurable, which might explain why the adherence rates were pretty high in this trial.
KELLIE NEWSOME: Linda Carpenter, MD, 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, transcranial magnetic stimulation, transcranial direct current stimulation, and esketamine. The Carlat Report is not just a podcast. Around one in five psychiatrists in the US subscribe to one of our journals. They are full of practical summaries and research updates, with special editions for general psychiatry, child psychiatry, addictions, hospital psychiatry, and psychotherapy. Subscribe online and get $30 off your first-year subscription with the promo code PODCAST.
CHRIS AIKEN: So ProLiv and TMS are both neurostimulation devices. ProLiv, I understand, is stimulating the cranial nerves and getting into the brain indirectly, and TMS is directly stimulating the cortex. Tell us more about how these two devices differ in their mechanisms.
LINDA CARPENTER: We really don't know how any antidepressant pill or stimulation ultimately changes the brain, but we do know a lot of things they do to the brain, and we can infer from them. So TMS, magnetic energy pulses through the scalp and the skull and all the tissues unimpeded, and then on the surface of the brain, called the cortex, an area of neurons is activated. It actually induces current in your brain. So you can induce this current, and you've got them activated and firing, and then they're in networks, and we know that connections between these networks are abnormal in people with depression/anxiety, they're either hyper-connected or they're under-connected; and this area is supposed to be telling the amygdala, “Be quiet. I don't wanna hear the anxiety right now because the house is not on fire, but it's not working”, and those signals are coming through. We think that it's attacking these networks like that.
CHRIS AIKEN: And how does ProLiv’s mechanism compare to Flow, the tDCS?
LINDA CARPENTER: Flow is what we call transcranial direct current stimulation. Now, the difference with Flow is that its mechanism is to shunt current from one area of the brain to another. The mechanisms for something like tDCS, or even for external combined occipital-trigeminal stimulation, and vagus nerve stimulation are much less worked out. But what we know from vagus nerve stimulation helps us understand how we believe the ProLiv, the Neuroleif product, works, and that is that these signals go through peripheral nerves to the brainstem, and have a regulating influence from the bottom up, in the solitary tract nucleus. There's kind of a highway in the brainstem to a lot of areas that regulate mood and anxiety disorders. You can get into the dorsal raphe, where there are serotonin neurons. You can get to norepinephrine neurons and a lot of other areas.
CHRIS AIKEN: Thank you, Dr. Carpenter. We talked today about the theory behind ProLivRx, but its actual discovery was more happenstance. The device was originally developed to treat migraines, and it does. It was FDA-cleared as Relivion in 2021 for migraines. Now, depression and migraines often go together, and while using it for migraines, researchers noticed an unexpected side effect: improvement in mood. With only one study behind ProLivRx, a lot is still unknown about this treatment. The effect size of 0.8 suggests that it makes a meaningful difference, although only 21% of those treated achieved full remission at eight weeks. In Dr. Carpenter's work, that effect did keep building if people used it longer than eight weeks, so there might be people who had delayed effects. But how long do these benefits last? Will it work in bipolar depression? In the clinical trial, it did not cause hypomania or mania, something we can't say for the Flow transcranial direct current stimulation device, as these tDCS machines cause mood switching for about 1 in 30 patients, which is like five times more often than the sham in those studies. ProLivRx also does not burn the skin. That's another risk with Flow, which can cause mild skin burns from the electricity. And ProLivRx does not cause seizures, which is a very rare risk with TMS. It did not impair cognition, and it does not cause insomnia. Although the treatment is a bit time-consuming, it requires an hour and 20 minutes a day. Patients seem to like ProLivRx. They found the mild stimulation relaxing and pleasurable, which might explain why the adherence rates were pretty high in this trial.
KELLIE NEWSOME: Linda Carpenter, MD, 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, transcranial magnetic stimulation, transcranial direct current stimulation, and esketamine. The Carlat Report is not just a podcast. Around one in five psychiatrists in the US subscribe to one of our journals. They are full of practical summaries and research updates, with special editions for general psychiatry, child psychiatry, addictions, hospital psychiatry, and psychotherapy. Subscribe online and get $30 off your first-year subscription with the promo code PODCAST.
