• Sleep Aids Can Be Uneven and Expensive, Leaving Anxious Patients Lacking

    May 21, 20255 min readOne Woman’s Pharmaceutical Journey to a Good Night’s SleepWhen insomnia took hold of this journalist, she relied on her science reporting to find a medication thatworkedBy Rachel Nuwer Malte MuellerThis Nature Outlook is editorially independent, produced with financial support from Avadel.I never had issues with sleep until the COVID-19 pandemic. A couple of months into lockdown in 2020, I found myself unable to fall or stay asleep. My worries played on an unstoppable loop, and the longer I lay in bed, the more anxious I became about not sleeping. This vicious cycle left me exhausted. After a few months, I became depressed. It was time to get professional help.This was the start of a years-long odyssey to find an effective sleep aid without negative side effects. The first medication I tried was 50 milligrams of an antihistamine called hydroxyzine, prescribed to me after a five-minute telehealth appointment. It effectively knocked me out, but it left me feeling so groggy the next morning that I struggled to get out of bed. I stopped taking it.On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.I lacked the energy to meet with a physician again, so I went back to relying on a grab bag of pills. These included over-the-counter melatonin, a hormone used to treat sleep problems; diphenhydramine, an antihistamine and sedative commonly sold as Benadryl; my husband’s gabapentin, which is prescribed to treat epilepsy and nerve pain but is commonly given as an anti-anxiety sleep aid; and tablets of questionable provenance that were labelled as alprazolam, used to treat anxiety conditions, which I acquired on a pre-pandemic trip to Sri Lanka. I rotated through these remedies in an attempt to not become overly reliant on any one of them.Last year, my struggle to sleep markedly worsened. Stress still seemed to be in limitless supply. My identity is wrapped up in my job as a science journalist, but as the media industry continues to collapse in on itself, it is becoming more and more difficult to make ends meet. At night, my chest would tighten as I tried to imagine a viable future in my chosen career. Layered on top of that were the stressors of the 2024 US presidential election and interpersonal drama with my increasingly conservative father.I found a sympathetic primary-care provider in the form of a physician’s assistant— a licensed medical professional who, in some states, can prescribe medications but isn’t actually a physician. She listened to my problems and asked me questions about my life. At the end of the appointment, she agreed that I should try the antidepressant bupropion. I was still having trouble sleeping, however, and my night-time anxiety spiked following the election. “Sadly, we are getting a lot of these messages,” my PA said when I told her about this. We added buspirone, an anti-anxiety medication, to my daily regimen. I immediately started sleeping better. But buspirone left me feeling deflated, numb and unmotivated during the day. My PA suggested that, as long as I didn’t develop serious depressive thoughts, I should stick it out for a month to give my body time to adjust.I agreed to give it more time. Then, about three weeks in, I woke up one night from a nightmare and felt something crawling through my hair. Then, I saw a flash of light, as though someone was standing over me taking a photograph. I quickly realized that these had been hallucinations that occurred in the transition from sleep to wakefulness. Nothing like this had ever happened to me before, and the vividness of the experience was extremely disconcerting. The next day, I learnt that disturbed sleep is a side effect of buspirone. My PA agreed that I should stop the drug.But, I still needed help to fall asleep. The obvious choice would have been benzodiazepines or ‘Z-drugs’ — classes of medications that have a sedative effect. But these drugs can also lead to dependency. Worryingly, too, a study in mice, published this year, found that one of these drugs, zolpidem, might interfere with the brain’s ability to clear waste, including toxic molecules associated with Alzheimer’s disease. These results still need to be replicated in humans, but they do mirror findings from at least one observational study. I told my PA I wanted to steer clear of these medications.Through reporting for another story on sleep medication for this Nature Outlook, I was cautiously excited to learn about a new class of insomnia medications known as dual orexin receptor antagonistdrugs. These work by blocking a molecule that promotes wakefulness, and they have fewer side effects and a lower risk of dependence compared with other sleep aids. My PA was familiar with one of them, Belsomra, and said I could try it.It took almost three weeks for me to receive the prescription, and my insurance would not cover it. There are no generic DORA drugs. Thirty daily tablets of Belsomra was going to cost me an astronomical USBut, I was desperate to get some sleep and my pharmacist was able to find a coupon that knocked off the bill. I sucked it up and paid.As I write this, I’ve been taking Belsomra on and off for a month. When it works well, I fall asleep quickly and soundly, and wake up feeling clear-headed and rested. About one-quarter of the time, however, my anxiety manages to cut through the medication and I struggle to fall asleep. My PA said that I can try doubling my dose to the maximum 20 milligrams, by taking two tablets each night. But I haven’t tried this yet, because I’m aware that each pill I pop before bed is about the same price as ordering a fancy cocktail.I held out hope that my health-insurance company, one of the largest in the United States, would eventually agree to cover Belsomra. The initial rejection note that the company sent included a list of eight cheaper, generic Z-drugs and benzodiazepines — all have a risk of dependency — that they required me to try first. My PA and I worked through the list of prescriptions in an effort to make a case that none of them were suitable. And finally, in late March, we had success: the insurance company agreed to pay for Belsomra for the next year. Even with that coverage, however, I’m still required to pay a steep for a month’s supply of the drug, which my pharmacist confirmed is normal for this medication. So, until a generic DORA drug comes out, this particular sleep solution will unfortunately be available only for those who have enough extra income to be able to pay for the privilege.I’m certainly aware that my trials and tribulations with insomnia have benefited from a tremendous amount of privilege. I have found an understanding and supportive PA, and my insurance pays for my appointments with her. I live in a country where these medications are available — DORA drugs are not available everywhere yet and I have enough disposable income to pay hundreds of dollars in the interest of self-care. I also have a level of education, and a job as a science journalist, that allows me to access and comprehend the latest health-care findings, and speak directly with scientists at the forefront of research. I can only imagine the collective exhaustion and frustration of the hundreds of millions of people around the world who are not in my position, and who are struggling on their own to get a good night’s sleep.It should not be like this. Medical professionals should be the ones calling the shots on what care their patients need — not insurance companies that are focused on ringing out as much profit as possible from clients who are already paying exorbitant premiums. However, until the system changes, millions of people will continue to take the same tortuous path that I have been forced onto, and resort to medications that might have harmful long-term effects while the most advanced therapies remain tantalizingly out of financial reach.
    #sleep #aids #can #uneven #expensive
    Sleep Aids Can Be Uneven and Expensive, Leaving Anxious Patients Lacking
    May 21, 20255 min readOne Woman’s Pharmaceutical Journey to a Good Night’s SleepWhen insomnia took hold of this journalist, she relied on her science reporting to find a medication thatworkedBy Rachel Nuwer Malte MuellerThis Nature Outlook is editorially independent, produced with financial support from Avadel.I never had issues with sleep until the COVID-19 pandemic. A couple of months into lockdown in 2020, I found myself unable to fall or stay asleep. My worries played on an unstoppable loop, and the longer I lay in bed, the more anxious I became about not sleeping. This vicious cycle left me exhausted. After a few months, I became depressed. It was time to get professional help.This was the start of a years-long odyssey to find an effective sleep aid without negative side effects. The first medication I tried was 50 milligrams of an antihistamine called hydroxyzine, prescribed to me after a five-minute telehealth appointment. It effectively knocked me out, but it left me feeling so groggy the next morning that I struggled to get out of bed. I stopped taking it.On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.I lacked the energy to meet with a physician again, so I went back to relying on a grab bag of pills. These included over-the-counter melatonin, a hormone used to treat sleep problems; diphenhydramine, an antihistamine and sedative commonly sold as Benadryl; my husband’s gabapentin, which is prescribed to treat epilepsy and nerve pain but is commonly given as an anti-anxiety sleep aid; and tablets of questionable provenance that were labelled as alprazolam, used to treat anxiety conditions, which I acquired on a pre-pandemic trip to Sri Lanka. I rotated through these remedies in an attempt to not become overly reliant on any one of them.Last year, my struggle to sleep markedly worsened. Stress still seemed to be in limitless supply. My identity is wrapped up in my job as a science journalist, but as the media industry continues to collapse in on itself, it is becoming more and more difficult to make ends meet. At night, my chest would tighten as I tried to imagine a viable future in my chosen career. Layered on top of that were the stressors of the 2024 US presidential election and interpersonal drama with my increasingly conservative father.I found a sympathetic primary-care provider in the form of a physician’s assistant— a licensed medical professional who, in some states, can prescribe medications but isn’t actually a physician. She listened to my problems and asked me questions about my life. At the end of the appointment, she agreed that I should try the antidepressant bupropion. I was still having trouble sleeping, however, and my night-time anxiety spiked following the election. “Sadly, we are getting a lot of these messages,” my PA said when I told her about this. We added buspirone, an anti-anxiety medication, to my daily regimen. I immediately started sleeping better. But buspirone left me feeling deflated, numb and unmotivated during the day. My PA suggested that, as long as I didn’t develop serious depressive thoughts, I should stick it out for a month to give my body time to adjust.I agreed to give it more time. Then, about three weeks in, I woke up one night from a nightmare and felt something crawling through my hair. Then, I saw a flash of light, as though someone was standing over me taking a photograph. I quickly realized that these had been hallucinations that occurred in the transition from sleep to wakefulness. Nothing like this had ever happened to me before, and the vividness of the experience was extremely disconcerting. The next day, I learnt that disturbed sleep is a side effect of buspirone. My PA agreed that I should stop the drug.But, I still needed help to fall asleep. The obvious choice would have been benzodiazepines or ‘Z-drugs’ — classes of medications that have a sedative effect. But these drugs can also lead to dependency. Worryingly, too, a study in mice, published this year, found that one of these drugs, zolpidem, might interfere with the brain’s ability to clear waste, including toxic molecules associated with Alzheimer’s disease. These results still need to be replicated in humans, but they do mirror findings from at least one observational study. I told my PA I wanted to steer clear of these medications.Through reporting for another story on sleep medication for this Nature Outlook, I was cautiously excited to learn about a new class of insomnia medications known as dual orexin receptor antagonistdrugs. These work by blocking a molecule that promotes wakefulness, and they have fewer side effects and a lower risk of dependence compared with other sleep aids. My PA was familiar with one of them, Belsomra, and said I could try it.It took almost three weeks for me to receive the prescription, and my insurance would not cover it. There are no generic DORA drugs. Thirty daily tablets of Belsomra was going to cost me an astronomical USBut, I was desperate to get some sleep and my pharmacist was able to find a coupon that knocked off the bill. I sucked it up and paid.As I write this, I’ve been taking Belsomra on and off for a month. When it works well, I fall asleep quickly and soundly, and wake up feeling clear-headed and rested. About one-quarter of the time, however, my anxiety manages to cut through the medication and I struggle to fall asleep. My PA said that I can try doubling my dose to the maximum 20 milligrams, by taking two tablets each night. But I haven’t tried this yet, because I’m aware that each pill I pop before bed is about the same price as ordering a fancy cocktail.I held out hope that my health-insurance company, one of the largest in the United States, would eventually agree to cover Belsomra. The initial rejection note that the company sent included a list of eight cheaper, generic Z-drugs and benzodiazepines — all have a risk of dependency — that they required me to try first. My PA and I worked through the list of prescriptions in an effort to make a case that none of them were suitable. And finally, in late March, we had success: the insurance company agreed to pay for Belsomra for the next year. Even with that coverage, however, I’m still required to pay a steep for a month’s supply of the drug, which my pharmacist confirmed is normal for this medication. So, until a generic DORA drug comes out, this particular sleep solution will unfortunately be available only for those who have enough extra income to be able to pay for the privilege.I’m certainly aware that my trials and tribulations with insomnia have benefited from a tremendous amount of privilege. I have found an understanding and supportive PA, and my insurance pays for my appointments with her. I live in a country where these medications are available — DORA drugs are not available everywhere yet and I have enough disposable income to pay hundreds of dollars in the interest of self-care. I also have a level of education, and a job as a science journalist, that allows me to access and comprehend the latest health-care findings, and speak directly with scientists at the forefront of research. I can only imagine the collective exhaustion and frustration of the hundreds of millions of people around the world who are not in my position, and who are struggling on their own to get a good night’s sleep.It should not be like this. Medical professionals should be the ones calling the shots on what care their patients need — not insurance companies that are focused on ringing out as much profit as possible from clients who are already paying exorbitant premiums. However, until the system changes, millions of people will continue to take the same tortuous path that I have been forced onto, and resort to medications that might have harmful long-term effects while the most advanced therapies remain tantalizingly out of financial reach. #sleep #aids #can #uneven #expensive
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    Sleep Aids Can Be Uneven and Expensive, Leaving Anxious Patients Lacking
    May 21, 20255 min readOne Woman’s Pharmaceutical Journey to a Good Night’s SleepWhen insomnia took hold of this journalist, she relied on her science reporting to find a medication that (mostly) workedBy Rachel Nuwer Malte MuellerThis Nature Outlook is editorially independent, produced with financial support from Avadel.I never had issues with sleep until the COVID-19 pandemic. A couple of months into lockdown in 2020, I found myself unable to fall or stay asleep. My worries played on an unstoppable loop, and the longer I lay in bed, the more anxious I became about not sleeping. This vicious cycle left me exhausted. After a few months, I became depressed. It was time to get professional help.This was the start of a years-long odyssey to find an effective sleep aid without negative side effects. The first medication I tried was 50 milligrams of an antihistamine called hydroxyzine, prescribed to me after a five-minute telehealth appointment. It effectively knocked me out, but it left me feeling so groggy the next morning that I struggled to get out of bed. I stopped taking it.On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.I lacked the energy to meet with a physician again, so I went back to relying on a grab bag of pills. These included over-the-counter melatonin, a hormone used to treat sleep problems; diphenhydramine, an antihistamine and sedative commonly sold as Benadryl; my husband’s gabapentin, which is prescribed to treat epilepsy and nerve pain but is commonly given as an anti-anxiety sleep aid; and tablets of questionable provenance that were labelled as alprazolam, used to treat anxiety conditions, which I acquired on a pre-pandemic trip to Sri Lanka. I rotated through these remedies in an attempt to not become overly reliant on any one of them.Last year, my struggle to sleep markedly worsened. Stress still seemed to be in limitless supply. My identity is wrapped up in my job as a science journalist, but as the media industry continues to collapse in on itself, it is becoming more and more difficult to make ends meet. At night, my chest would tighten as I tried to imagine a viable future in my chosen career. Layered on top of that were the stressors of the 2024 US presidential election and interpersonal drama with my increasingly conservative father.I found a sympathetic primary-care provider in the form of a physician’s assistant (PA) — a licensed medical professional who, in some states, can prescribe medications but isn’t actually a physician. She listened to my problems and asked me questions about my life. At the end of the appointment, she agreed that I should try the antidepressant bupropion. I was still having trouble sleeping, however, and my night-time anxiety spiked following the election. “Sadly, we are getting a lot of these messages,” my PA said when I told her about this. We added buspirone, an anti-anxiety medication, to my daily regimen. I immediately started sleeping better. But buspirone left me feeling deflated, numb and unmotivated during the day. My PA suggested that, as long as I didn’t develop serious depressive thoughts, I should stick it out for a month to give my body time to adjust.I agreed to give it more time. Then, about three weeks in, I woke up one night from a nightmare and felt something crawling through my hair. Then, I saw a flash of light, as though someone was standing over me taking a photograph. I quickly realized that these had been hallucinations that occurred in the transition from sleep to wakefulness. Nothing like this had ever happened to me before, and the vividness of the experience was extremely disconcerting. The next day, I learnt that disturbed sleep is a side effect of buspirone. My PA agreed that I should stop the drug.But, I still needed help to fall asleep. The obvious choice would have been benzodiazepines or ‘Z-drugs’ — classes of medications that have a sedative effect. But these drugs can also lead to dependency. Worryingly, too, a study in mice, published this year, found that one of these drugs, zolpidem (Ambien), might interfere with the brain’s ability to clear waste, including toxic molecules associated with Alzheimer’s disease. These results still need to be replicated in humans, but they do mirror findings from at least one observational study. I told my PA I wanted to steer clear of these medications.Through reporting for another story on sleep medication for this Nature Outlook, I was cautiously excited to learn about a new class of insomnia medications known as dual orexin receptor antagonist (DORA) drugs. These work by blocking a molecule that promotes wakefulness, and they have fewer side effects and a lower risk of dependence compared with other sleep aids. My PA was familiar with one of them, Belsomra, and said I could try it.It took almost three weeks for me to receive the prescription, and my insurance would not cover it. There are no generic DORA drugs. Thirty daily tablets of Belsomra was going to cost me an astronomical US$500. But, I was desperate to get some sleep and my pharmacist was able to find a coupon that knocked $150 off the bill. I sucked it up and paid.As I write this, I’ve been taking Belsomra on and off for a month. When it works well, I fall asleep quickly and soundly, and wake up feeling clear-headed and rested. About one-quarter of the time, however, my anxiety manages to cut through the medication and I struggle to fall asleep. My PA said that I can try doubling my dose to the maximum 20 milligrams, by taking two tablets each night. But I haven’t tried this yet, because I’m aware that each pill I pop before bed is about the same price as ordering a fancy cocktail.I held out hope that my health-insurance company, one of the largest in the United States, would eventually agree to cover Belsomra. The initial rejection note that the company sent included a list of eight cheaper, generic Z-drugs and benzodiazepines — all have a risk of dependency — that they required me to try first. My PA and I worked through the list of prescriptions in an effort to make a case that none of them were suitable. And finally, in late March, we had success: the insurance company agreed to pay for Belsomra for the next year. Even with that coverage, however, I’m still required to pay a steep $150 for a month’s supply of the drug, which my pharmacist confirmed is normal for this medication. So, until a generic DORA drug comes out, this particular sleep solution will unfortunately be available only for those who have enough extra income to be able to pay for the privilege.I’m certainly aware that my trials and tribulations with insomnia have benefited from a tremendous amount of privilege. I have found an understanding and supportive PA, and my insurance pays for my appointments with her. I live in a country where these medications are available — DORA drugs are not available everywhere yet and I have enough disposable income to pay hundreds of dollars in the interest of self-care. I also have a level of education, and a job as a science journalist, that allows me to access and comprehend the latest health-care findings, and speak directly with scientists at the forefront of research. I can only imagine the collective exhaustion and frustration of the hundreds of millions of people around the world who are not in my position, and who are struggling on their own to get a good night’s sleep.It should not be like this. Medical professionals should be the ones calling the shots on what care their patients need — not insurance companies that are focused on ringing out as much profit as possible from clients who are already paying exorbitant premiums. However, until the system changes, millions of people will continue to take the same tortuous path that I have been forced onto, and resort to medications that might have harmful long-term effects while the most advanced therapies remain tantalizingly out of financial reach.
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  • New Class of Drugs Blocks Wakefulness Chemical and Offers Relief from Insomnia

    May 21, 202510 min readSleep Better with New Drugs, Select Cannabinoids and Wearable DevicesDrugs that target wakefulness, molecules in cannabis and wearable devices that modulate brain activity could help people with insomniaBy Rachel Nuwer carlofranco/Getty ImagesThis Nature Outlook is editorially independent, produced with financial support from Avadel.Miranda cannot remember a time in her life when she did not have insomnia. The 23 year old, who asked for her last name to be withheld, started struggling with sleep when she was a child. As she’s grown older, it’s only become worse. She takes “a myriad of medications” each night, she says, but usually still cannot fall asleep until the early hours of the morning. “I can’t get up and be functional until halfway through the day,” she says. She had to drop out of university because she couldn’t attend classes, and she can’t hold down a job. Her insomnia exacerbates other medical conditions as well, including migraines and the pain condition fibromyalgia. “It’s hugely debilitating,” she says. “It affects everything.”In the United States, about 12% of adults have been diagnosed with chronic insomnia — when a person struggles to sleep for more than three nights each week for at least three months, and experiences daytime distress as a result. Research suggests that the worldwide figure is 10–30%. It also often co-occurs with and creates a vicious cycle with other conditions, including chronic pain, depression and anxiety.On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.Fortunately for Miranda and millions of others with chronic insomnia, new treatments are arriving. The emergence of a class of pharmaceuticals that induces sleep through a different brain pathway from existing drugs is a welcome development, and molecules in cannabis and specialized medical devices to promote sleep are also showing potential as sleep aids. Soon, those struggling with sleep could have a range of new options available to help.Imperfect solutionsCognitive behavioural therapy for insomniais usually the recommended first treatment. This specialized talking therapy focuses on establishing healthy sleep behaviours and addressing thoughts that can interfere with sleep. But CBT-I is not covered by all health-care insurance plans in the United States. In the United Kingdom and parts of Europe, public health-care systems usually provide it, but waiting times can be long. This is because, around the world, there is a limited availability of therapists, says Andrew Krystal, a psychiatrist at the University of California, San Francisco. “We keep hiring new people, but almost immediately their schedules are completely filled and the wait list is a year.”CBT-I also doesn’t work for everyone. Miranda has tried it and has received conventional talking therapy for over a decade, with limited success. “It only helps so much,” she says.Pharmacological interventions are the next line of defence, Krystal says. Benzodiazepines and a class of medicines called Z-drugs, which include zolpidem, are among the most prescribed insomnia medications. These sedative hypnotics enhance the effects of the neurotransmitter GABA, thereby dampening brain activity. They also reduce anxiety. But they can create a hangover effect and increase the risk of falls in older people. These drugs also have the potential for misuse and can cause dependence. Some studies have even found an association between long-term use of Z-drugs and benzodiazepines and an increased risk of death.Miranda tried Ambien, but says that she quickly became chemically dependent. She eventually weaned herself off it and switched to benzodiazepines, but she began developing a tolerance to them, too — she once wound up in hospital with withdrawal symptoms after she tried to cut back on her dosage. “They’re horrible drugs to be on,” she says. But she cannot fall asleep without them. Each night, she now takes two benzodiazepines, as well as gabapentin, an anticonvulsant medication that is sometimes given off-label for insomnia.Physicians frequently provide other off-label prescriptions for insomnia, including trazodone, which is approved for depression. Over-the-counter products such as antihistamines are also used for sleeplessness. None are ideal, however, because they have not been evaluated as sleep aids, says Emmanuel Mignot, a sleep-medicine researcher at Stanford University in California.Miranda has experience with many of these products. When she first developed chronic insomnia as a child, her paediatrician recommended melatonin, which is available without a prescription in the United States. It helped her fall asleep, but it did not keep her asleep. During her teenage years, different neurologists prescribed off-label antidepressants and other mood medications, including trazodone and mirtazapine. But they came with what she calls “torturous” side effects: she felt constantly anxious and exhausted during the day, and her memory became “incredibly foggy”.Blocking wakefulnessMignot was studying narcolepsy, a chronic disorder that affects sleep–wake cycles and causes people to fall asleep suddenly, when he inadvertently helped to pave the way towards the latest means of treating insomnia. He discovered that dogs with narcolepsy have a genetic mutation that affects one of two receptors used by the neurotransmitter orexin, the primary role of which was initially thought to be the regulation of appetite. Mignot then found that people with narcolepsy lack orexin, confirming the chemical’s main job: promoting wakefulness. If drugs could be developed to prevent orexin from binding to its receptors, Mignot thought, then people with insomnia would become “narcoleptic for one night”.In 2007, researchers at the pharmaceutical firm Actelionshowed that blocking orexin’s two receptors induced sleep in rats, dogs and people. In 2014, the biopharmaceutical company Merck, received US Food and Drug Administrationapproval for the first dual orexin receptor antagonistdrug, suvorexant. In 2019, another DORA drug — lemborexant— was approved, followed, in 2022, by daridorexant.Compared with benzodiazepines and Z-drugs, which inhibit activity all over the brain, DORA drugs affect only the neurons activated by orexins. “The beauty of it is it does nothing but block the stimulation of wakefulness,” says neurologist Joe Herring, who heads neuroscience clinical research at Merck in Rahway, New Jersey. “It’s a physiologically better way to promote sleep.”Alisdair Macdonald/NatureDaridorexant is the only DORA drug for which data are available about daytime functioning, says Antonio Olivieri, chief medical officer at Idorsia, which produces daridorexant. In clinical trials, Idorsia showed that, compared with those given a placebo, people who received daridorexant experienced significant improvements in daytime insomnia symptoms the following day. Data reported in the approvals database of the FDA also indicate that daridorexant has the lowest fatigue and drowsiness scores of the three DORA drugs, possibly because it leaves the body the quickest.So far, there have been no one-to-one comparisons of DORA drugs. “Ideally, you’d have direct evidence of how those drugs compare to each other,” says Daniel Buysse, a sleep scientist at the University of Pittsburgh School of Medicine in Pennsylvania. “But we rarely have such evidence, so instead, we have to rely on statistical techniques that allow you to make indirect comparisons.” It’s also difficult to say definitively how DORA drugs compare with older treatments for insomnia, but Buysse says that drug registration trials suggest that DORA drugs have fewer adverse cognitive or hangover effects compared with benzodiazepines and Z-drugs, as well as less potential for dependence and misuse. The European Insomnia Guideline 2023 placed daridorexant as the next recommended insomnia treatment after CBT-I.The main drawback to DORA drugs, Buysse says, is not medical but financial: their high cost keeps them out of reach of many people who could benefit from them. “There are many patients I would like to prescribe these drugs for, but I know in order for them to get one of these medications we’ll have to go through trials of several other drugs before the request will be considered,” Buysse says. DORA drugs are also available only in a few countries, so far.Given her long history of insomnia, Miranda was given a prescription for suvorexant. Her psychiatrist recommended the drug to her about a year ago. “I was really sceptical that an anti-wakefulness drug would be any different to a pro-sleep drug,” she says. But she quickly felt the difference, and has now come to see the drug as “a saviour”. Without the drug, she says, “I’d probably be on a much higher benzodiazepine dose than I am.” She hopes her suvorexant dose can continue to increase, so that some of her other medications can be reduced.Expanding availabilityOther drugs that target the orexin system are in the clinical pipeline. Seltorexant, for example, is being developed by the US pharmaceutical firm Johnson & Johnson for people with both major depressive disorder and insomnia. Around 70% of people with depression have insomnia, so having a medication that treats both of those disorders “has the potential to fill an important gap”, says Krystal, who has consulted for Johnson & Johnson on the drug. In a phase III trial, participants who took the drug experienced meaningful improvement in both sleep and depressive symptoms, with an antidepressant effect that seemed to be independent of the participants getting better sleep. Seltorexant might have an antidepressant effect because it is designed to block only one of the two types of orexin receptor, Krystal adds, whereas other DORA drugs block both receptor types.Investigations of already-approved DORA drugs are also expanding into other populations. Merck has sponsored investigator-led studies of suvorexant in people with insomnia as well as depression or substance-use disorders, and Idorsia is sponsoring studies of daridorexant’s safety and efficacy in sub-groups of people who have insomnia and other conditions.In 2020, suvorexant became the first medication to be approved for treating sleep disorders in people with Alzheimer’s disease. Insomnia is often a precursor to and co-morbid with Alzheimer’s, and the disease seems to manifest differently in people with the condition. In one study comparing older people with insomnia with those with both insomnia and Alzheimer’s, people with both conditions had a number of extra changes to their sleep patterns, including less time spent in deep sleep — sometimes called slow-wave sleep because that describes the pattern of the brain’s electrical activity during these intervals. Sleep problems in people with Alzheimer’s also seem to have a causal role in increasing levels of toxic substances in the brains of those individuals. Preliminary data suggest that suvorexant could also help to reduce toxic brain proteins. The results of a follow-up study testing that finding are expected in 2026.In the weedsSleeplessness is already among the most common conditions for the medicinal use of the drug cannabis. Miranda, for example, supplements her nightly pharmaceutical regimen with a cannabis tincture that contains a few of the plant’s 100-plus cannabinoids. “It’s definitely a key player in my sleep-medication arsenal,” she says.Yet, scientifically, little is known about which cannabinoids — if any — promote sleep, and what a safe and effective dose is. “Tens of millions of people around the world are probably using cannabinoids for insomnia, but we have very little good-quality evidence to support that,” says Iain McGregor, director of the Lambert Initiative for Cannabinoid Therapeutics at the University of Sydney in Australia.McGregor is investigating cannabinol, a molecule that develops in cannabis as the psychoactive component tetrahydrocannabinoloxidizes. His group reported that CBN increased sleep in rats to a similar degree as zolpidem, but without the drug’s known negative side effect of suppressing rapid-eye-movement sleep. Unpublished data of a single-night trial with 20 people with insomnia disorder show that people fell asleep 7 minutes faster after taking 300 milligrams of CBN compared with those taking a placebo; participants also reported subjective improvements in sleep and mood. Although 7 minutes “doesn’t sound like a lot”, it is on a par with what benzodiazepines and Z-drugs typically accomplish, says Camilla Hoyos, a sleep researcher at the Woolcock Institute of Medical Research in Sydney, who led the work. McGregor, Hoyos and their colleagues are aiming to follow up the work with a large, community-based trial in which people with insomnia take either CBN or a placebo for six weeks at home.As for cannabidioland THC — the most well-known cannabinoids — the prospects for efficacy against insomnia are doubtful, at least for the doses used in trials so far. Several small studies have failed to find a sleep benefit from taking CBD. In one experiment, researchers observed that participants in a study who received 10 milligrams of THC and 200 milligrams of CBD actually slept for 25 minutes less compared with when they received a placebo. Several other company-sponsored trials of low-dose CBD for insomnia were not published, McGregor adds, because they found no significant improvement. “It’s been one failure after the next,” he says.Insomnia’s new frontiersThe search for more effective insomnia treatments continues in other realms, as well. Some research groups are experimenting with different receptors that they hope could lead to new classes of drugs. Gabriella Gobbi, a clinical psychiatrist and research neuroscientist at McGill University in Montreal, Canada, for example, has homed in on one of the brain’s two melatonin receptors, MT2. “We want to find an alternative mechanism without any addiction liability and with fewer side effects, especially for use in children and elderly people,” she says. A molecule that the team developed that binds to MT2 increased the time that rats spent in deep sleep by 30%. Gobbi aims to launch clinical trials in the next two to three years.A few companies and health systems, including the US Department of Veterans Affairs and the Cleveland Clinic in Ohio, have also created or are developing digital platforms for delivering CBT-I. These apps take users through regimens that are tailored to their symptoms. SleepioRx, for example, is a 90-day digital programme that has been evaluated in more than two dozen clinical trials and has showed efficacy as high as 76%. This includes helping people to fall asleep faster, sleep better throughout the night and feel better the next day. In August 2024, the programme, developed by Big Health in San Francisco, California, received FDA clearance. A 2024 meta-analysis of 15 studies that compare in-person and electronically delivered CBT-I concluded that the two approaches were equally effective.Uptake among physicians has been slow so far, Krystal says. But once practitioners catch on, he adds, “I can imagine a world where you have digital care as your first stop, and if that’s not successful, you see a therapist.”Some studies suggest that insomnia can stem from a high level of underlying brain activity during sleep. This raises the question of whether reducing this activity could treat insomnia, says Ruth Benca, a psychiatrist at Wake Forest School of Medicine in North Carolina. Companies and academic research groups are beginning to test this proposition with wearable devices that use auditory tones or mild electrical stimulation to increase slow-wave activity in the brain. Some devices are already on the market, and evidence suggests that they can increase the duration of deep sleep. Last June, for example, researchers at Elemind Technologies in Cambridge, Massachusetts, confirmed that auditory stimuli delivered in sync with specific brain-wave rhythms generated in a headband allowed people who usually struggle for more than 30 minutes to fall asleep to shave an average of 10.5 minutes off that time.In the coming years, according to Benca, researchers hope to learn enough about insomnia’s causes and treatments to be able to recommend personalized therapies based on an individual’s specific demographics, genetics and co-morbidities. These are the frontiers people are working at, she says.Even after a lifetime of struggling to find safe and effective help, Miranda says that she still holds out hope that better treatments for insomnia are on the horizon. “I can’t be on these medications forever,” she says. “They’re going to take years off my life.”
    #new #class #drugs #blocks #wakefulness
    New Class of Drugs Blocks Wakefulness Chemical and Offers Relief from Insomnia
    May 21, 202510 min readSleep Better with New Drugs, Select Cannabinoids and Wearable DevicesDrugs that target wakefulness, molecules in cannabis and wearable devices that modulate brain activity could help people with insomniaBy Rachel Nuwer carlofranco/Getty ImagesThis Nature Outlook is editorially independent, produced with financial support from Avadel.Miranda cannot remember a time in her life when she did not have insomnia. The 23 year old, who asked for her last name to be withheld, started struggling with sleep when she was a child. As she’s grown older, it’s only become worse. She takes “a myriad of medications” each night, she says, but usually still cannot fall asleep until the early hours of the morning. “I can’t get up and be functional until halfway through the day,” she says. She had to drop out of university because she couldn’t attend classes, and she can’t hold down a job. Her insomnia exacerbates other medical conditions as well, including migraines and the pain condition fibromyalgia. “It’s hugely debilitating,” she says. “It affects everything.”In the United States, about 12% of adults have been diagnosed with chronic insomnia — when a person struggles to sleep for more than three nights each week for at least three months, and experiences daytime distress as a result. Research suggests that the worldwide figure is 10–30%. It also often co-occurs with and creates a vicious cycle with other conditions, including chronic pain, depression and anxiety.On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.Fortunately for Miranda and millions of others with chronic insomnia, new treatments are arriving. The emergence of a class of pharmaceuticals that induces sleep through a different brain pathway from existing drugs is a welcome development, and molecules in cannabis and specialized medical devices to promote sleep are also showing potential as sleep aids. Soon, those struggling with sleep could have a range of new options available to help.Imperfect solutionsCognitive behavioural therapy for insomniais usually the recommended first treatment. This specialized talking therapy focuses on establishing healthy sleep behaviours and addressing thoughts that can interfere with sleep. But CBT-I is not covered by all health-care insurance plans in the United States. In the United Kingdom and parts of Europe, public health-care systems usually provide it, but waiting times can be long. This is because, around the world, there is a limited availability of therapists, says Andrew Krystal, a psychiatrist at the University of California, San Francisco. “We keep hiring new people, but almost immediately their schedules are completely filled and the wait list is a year.”CBT-I also doesn’t work for everyone. Miranda has tried it and has received conventional talking therapy for over a decade, with limited success. “It only helps so much,” she says.Pharmacological interventions are the next line of defence, Krystal says. Benzodiazepines and a class of medicines called Z-drugs, which include zolpidem, are among the most prescribed insomnia medications. These sedative hypnotics enhance the effects of the neurotransmitter GABA, thereby dampening brain activity. They also reduce anxiety. But they can create a hangover effect and increase the risk of falls in older people. These drugs also have the potential for misuse and can cause dependence. Some studies have even found an association between long-term use of Z-drugs and benzodiazepines and an increased risk of death.Miranda tried Ambien, but says that she quickly became chemically dependent. She eventually weaned herself off it and switched to benzodiazepines, but she began developing a tolerance to them, too — she once wound up in hospital with withdrawal symptoms after she tried to cut back on her dosage. “They’re horrible drugs to be on,” she says. But she cannot fall asleep without them. Each night, she now takes two benzodiazepines, as well as gabapentin, an anticonvulsant medication that is sometimes given off-label for insomnia.Physicians frequently provide other off-label prescriptions for insomnia, including trazodone, which is approved for depression. Over-the-counter products such as antihistamines are also used for sleeplessness. None are ideal, however, because they have not been evaluated as sleep aids, says Emmanuel Mignot, a sleep-medicine researcher at Stanford University in California.Miranda has experience with many of these products. When she first developed chronic insomnia as a child, her paediatrician recommended melatonin, which is available without a prescription in the United States. It helped her fall asleep, but it did not keep her asleep. During her teenage years, different neurologists prescribed off-label antidepressants and other mood medications, including trazodone and mirtazapine. But they came with what she calls “torturous” side effects: she felt constantly anxious and exhausted during the day, and her memory became “incredibly foggy”.Blocking wakefulnessMignot was studying narcolepsy, a chronic disorder that affects sleep–wake cycles and causes people to fall asleep suddenly, when he inadvertently helped to pave the way towards the latest means of treating insomnia. He discovered that dogs with narcolepsy have a genetic mutation that affects one of two receptors used by the neurotransmitter orexin, the primary role of which was initially thought to be the regulation of appetite. Mignot then found that people with narcolepsy lack orexin, confirming the chemical’s main job: promoting wakefulness. If drugs could be developed to prevent orexin from binding to its receptors, Mignot thought, then people with insomnia would become “narcoleptic for one night”.In 2007, researchers at the pharmaceutical firm Actelionshowed that blocking orexin’s two receptors induced sleep in rats, dogs and people. In 2014, the biopharmaceutical company Merck, received US Food and Drug Administrationapproval for the first dual orexin receptor antagonistdrug, suvorexant. In 2019, another DORA drug — lemborexant— was approved, followed, in 2022, by daridorexant.Compared with benzodiazepines and Z-drugs, which inhibit activity all over the brain, DORA drugs affect only the neurons activated by orexins. “The beauty of it is it does nothing but block the stimulation of wakefulness,” says neurologist Joe Herring, who heads neuroscience clinical research at Merck in Rahway, New Jersey. “It’s a physiologically better way to promote sleep.”Alisdair Macdonald/NatureDaridorexant is the only DORA drug for which data are available about daytime functioning, says Antonio Olivieri, chief medical officer at Idorsia, which produces daridorexant. In clinical trials, Idorsia showed that, compared with those given a placebo, people who received daridorexant experienced significant improvements in daytime insomnia symptoms the following day. Data reported in the approvals database of the FDA also indicate that daridorexant has the lowest fatigue and drowsiness scores of the three DORA drugs, possibly because it leaves the body the quickest.So far, there have been no one-to-one comparisons of DORA drugs. “Ideally, you’d have direct evidence of how those drugs compare to each other,” says Daniel Buysse, a sleep scientist at the University of Pittsburgh School of Medicine in Pennsylvania. “But we rarely have such evidence, so instead, we have to rely on statistical techniques that allow you to make indirect comparisons.” It’s also difficult to say definitively how DORA drugs compare with older treatments for insomnia, but Buysse says that drug registration trials suggest that DORA drugs have fewer adverse cognitive or hangover effects compared with benzodiazepines and Z-drugs, as well as less potential for dependence and misuse. The European Insomnia Guideline 2023 placed daridorexant as the next recommended insomnia treatment after CBT-I.The main drawback to DORA drugs, Buysse says, is not medical but financial: their high cost keeps them out of reach of many people who could benefit from them. “There are many patients I would like to prescribe these drugs for, but I know in order for them to get one of these medications we’ll have to go through trials of several other drugs before the request will be considered,” Buysse says. DORA drugs are also available only in a few countries, so far.Given her long history of insomnia, Miranda was given a prescription for suvorexant. Her psychiatrist recommended the drug to her about a year ago. “I was really sceptical that an anti-wakefulness drug would be any different to a pro-sleep drug,” she says. But she quickly felt the difference, and has now come to see the drug as “a saviour”. Without the drug, she says, “I’d probably be on a much higher benzodiazepine dose than I am.” She hopes her suvorexant dose can continue to increase, so that some of her other medications can be reduced.Expanding availabilityOther drugs that target the orexin system are in the clinical pipeline. Seltorexant, for example, is being developed by the US pharmaceutical firm Johnson & Johnson for people with both major depressive disorder and insomnia. Around 70% of people with depression have insomnia, so having a medication that treats both of those disorders “has the potential to fill an important gap”, says Krystal, who has consulted for Johnson & Johnson on the drug. In a phase III trial, participants who took the drug experienced meaningful improvement in both sleep and depressive symptoms, with an antidepressant effect that seemed to be independent of the participants getting better sleep. Seltorexant might have an antidepressant effect because it is designed to block only one of the two types of orexin receptor, Krystal adds, whereas other DORA drugs block both receptor types.Investigations of already-approved DORA drugs are also expanding into other populations. Merck has sponsored investigator-led studies of suvorexant in people with insomnia as well as depression or substance-use disorders, and Idorsia is sponsoring studies of daridorexant’s safety and efficacy in sub-groups of people who have insomnia and other conditions.In 2020, suvorexant became the first medication to be approved for treating sleep disorders in people with Alzheimer’s disease. Insomnia is often a precursor to and co-morbid with Alzheimer’s, and the disease seems to manifest differently in people with the condition. In one study comparing older people with insomnia with those with both insomnia and Alzheimer’s, people with both conditions had a number of extra changes to their sleep patterns, including less time spent in deep sleep — sometimes called slow-wave sleep because that describes the pattern of the brain’s electrical activity during these intervals. Sleep problems in people with Alzheimer’s also seem to have a causal role in increasing levels of toxic substances in the brains of those individuals. Preliminary data suggest that suvorexant could also help to reduce toxic brain proteins. The results of a follow-up study testing that finding are expected in 2026.In the weedsSleeplessness is already among the most common conditions for the medicinal use of the drug cannabis. Miranda, for example, supplements her nightly pharmaceutical regimen with a cannabis tincture that contains a few of the plant’s 100-plus cannabinoids. “It’s definitely a key player in my sleep-medication arsenal,” she says.Yet, scientifically, little is known about which cannabinoids — if any — promote sleep, and what a safe and effective dose is. “Tens of millions of people around the world are probably using cannabinoids for insomnia, but we have very little good-quality evidence to support that,” says Iain McGregor, director of the Lambert Initiative for Cannabinoid Therapeutics at the University of Sydney in Australia.McGregor is investigating cannabinol, a molecule that develops in cannabis as the psychoactive component tetrahydrocannabinoloxidizes. His group reported that CBN increased sleep in rats to a similar degree as zolpidem, but without the drug’s known negative side effect of suppressing rapid-eye-movement sleep. Unpublished data of a single-night trial with 20 people with insomnia disorder show that people fell asleep 7 minutes faster after taking 300 milligrams of CBN compared with those taking a placebo; participants also reported subjective improvements in sleep and mood. Although 7 minutes “doesn’t sound like a lot”, it is on a par with what benzodiazepines and Z-drugs typically accomplish, says Camilla Hoyos, a sleep researcher at the Woolcock Institute of Medical Research in Sydney, who led the work. McGregor, Hoyos and their colleagues are aiming to follow up the work with a large, community-based trial in which people with insomnia take either CBN or a placebo for six weeks at home.As for cannabidioland THC — the most well-known cannabinoids — the prospects for efficacy against insomnia are doubtful, at least for the doses used in trials so far. Several small studies have failed to find a sleep benefit from taking CBD. In one experiment, researchers observed that participants in a study who received 10 milligrams of THC and 200 milligrams of CBD actually slept for 25 minutes less compared with when they received a placebo. Several other company-sponsored trials of low-dose CBD for insomnia were not published, McGregor adds, because they found no significant improvement. “It’s been one failure after the next,” he says.Insomnia’s new frontiersThe search for more effective insomnia treatments continues in other realms, as well. Some research groups are experimenting with different receptors that they hope could lead to new classes of drugs. Gabriella Gobbi, a clinical psychiatrist and research neuroscientist at McGill University in Montreal, Canada, for example, has homed in on one of the brain’s two melatonin receptors, MT2. “We want to find an alternative mechanism without any addiction liability and with fewer side effects, especially for use in children and elderly people,” she says. A molecule that the team developed that binds to MT2 increased the time that rats spent in deep sleep by 30%. Gobbi aims to launch clinical trials in the next two to three years.A few companies and health systems, including the US Department of Veterans Affairs and the Cleveland Clinic in Ohio, have also created or are developing digital platforms for delivering CBT-I. These apps take users through regimens that are tailored to their symptoms. SleepioRx, for example, is a 90-day digital programme that has been evaluated in more than two dozen clinical trials and has showed efficacy as high as 76%. This includes helping people to fall asleep faster, sleep better throughout the night and feel better the next day. In August 2024, the programme, developed by Big Health in San Francisco, California, received FDA clearance. A 2024 meta-analysis of 15 studies that compare in-person and electronically delivered CBT-I concluded that the two approaches were equally effective.Uptake among physicians has been slow so far, Krystal says. But once practitioners catch on, he adds, “I can imagine a world where you have digital care as your first stop, and if that’s not successful, you see a therapist.”Some studies suggest that insomnia can stem from a high level of underlying brain activity during sleep. This raises the question of whether reducing this activity could treat insomnia, says Ruth Benca, a psychiatrist at Wake Forest School of Medicine in North Carolina. Companies and academic research groups are beginning to test this proposition with wearable devices that use auditory tones or mild electrical stimulation to increase slow-wave activity in the brain. Some devices are already on the market, and evidence suggests that they can increase the duration of deep sleep. Last June, for example, researchers at Elemind Technologies in Cambridge, Massachusetts, confirmed that auditory stimuli delivered in sync with specific brain-wave rhythms generated in a headband allowed people who usually struggle for more than 30 minutes to fall asleep to shave an average of 10.5 minutes off that time.In the coming years, according to Benca, researchers hope to learn enough about insomnia’s causes and treatments to be able to recommend personalized therapies based on an individual’s specific demographics, genetics and co-morbidities. These are the frontiers people are working at, she says.Even after a lifetime of struggling to find safe and effective help, Miranda says that she still holds out hope that better treatments for insomnia are on the horizon. “I can’t be on these medications forever,” she says. “They’re going to take years off my life.” #new #class #drugs #blocks #wakefulness
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    New Class of Drugs Blocks Wakefulness Chemical and Offers Relief from Insomnia
    May 21, 202510 min readSleep Better with New Drugs, Select Cannabinoids and Wearable DevicesDrugs that target wakefulness, molecules in cannabis and wearable devices that modulate brain activity could help people with insomniaBy Rachel Nuwer carlofranco/Getty ImagesThis Nature Outlook is editorially independent, produced with financial support from Avadel.Miranda cannot remember a time in her life when she did not have insomnia. The 23 year old, who asked for her last name to be withheld, started struggling with sleep when she was a child. As she’s grown older, it’s only become worse. She takes “a myriad of medications” each night, she says, but usually still cannot fall asleep until the early hours of the morning. “I can’t get up and be functional until halfway through the day,” she says. She had to drop out of university because she couldn’t attend classes, and she can’t hold down a job. Her insomnia exacerbates other medical conditions as well, including migraines and the pain condition fibromyalgia. “It’s hugely debilitating,” she says. “It affects everything.”In the United States, about 12% of adults have been diagnosed with chronic insomnia — when a person struggles to sleep for more than three nights each week for at least three months, and experiences daytime distress as a result. Research suggests that the worldwide figure is 10–30%. It also often co-occurs with and creates a vicious cycle with other conditions, including chronic pain, depression and anxiety.On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.Fortunately for Miranda and millions of others with chronic insomnia, new treatments are arriving. The emergence of a class of pharmaceuticals that induces sleep through a different brain pathway from existing drugs is a welcome development, and molecules in cannabis and specialized medical devices to promote sleep are also showing potential as sleep aids. Soon, those struggling with sleep could have a range of new options available to help.Imperfect solutionsCognitive behavioural therapy for insomnia (CBT-I) is usually the recommended first treatment. This specialized talking therapy focuses on establishing healthy sleep behaviours and addressing thoughts that can interfere with sleep. But CBT-I is not covered by all health-care insurance plans in the United States. In the United Kingdom and parts of Europe, public health-care systems usually provide it, but waiting times can be long. This is because, around the world, there is a limited availability of therapists, says Andrew Krystal, a psychiatrist at the University of California, San Francisco. “We keep hiring new people, but almost immediately their schedules are completely filled and the wait list is a year.”CBT-I also doesn’t work for everyone. Miranda has tried it and has received conventional talking therapy for over a decade, with limited success. “It only helps so much,” she says.Pharmacological interventions are the next line of defence, Krystal says. Benzodiazepines and a class of medicines called Z-drugs, which include zolpidem (Ambien), are among the most prescribed insomnia medications. These sedative hypnotics enhance the effects of the neurotransmitter GABA, thereby dampening brain activity. They also reduce anxiety. But they can create a hangover effect and increase the risk of falls in older people. These drugs also have the potential for misuse and can cause dependence. Some studies have even found an association between long-term use of Z-drugs and benzodiazepines and an increased risk of death.Miranda tried Ambien, but says that she quickly became chemically dependent. She eventually weaned herself off it and switched to benzodiazepines, but she began developing a tolerance to them, too — she once wound up in hospital with withdrawal symptoms after she tried to cut back on her dosage. “They’re horrible drugs to be on,” she says. But she cannot fall asleep without them. Each night, she now takes two benzodiazepines, as well as gabapentin, an anticonvulsant medication that is sometimes given off-label for insomnia.Physicians frequently provide other off-label prescriptions for insomnia, including trazodone, which is approved for depression. Over-the-counter products such as antihistamines are also used for sleeplessness. None are ideal, however, because they have not been evaluated as sleep aids, says Emmanuel Mignot, a sleep-medicine researcher at Stanford University in California.Miranda has experience with many of these products. When she first developed chronic insomnia as a child, her paediatrician recommended melatonin, which is available without a prescription in the United States. It helped her fall asleep, but it did not keep her asleep. During her teenage years, different neurologists prescribed off-label antidepressants and other mood medications, including trazodone and mirtazapine. But they came with what she calls “torturous” side effects: she felt constantly anxious and exhausted during the day, and her memory became “incredibly foggy”.Blocking wakefulnessMignot was studying narcolepsy, a chronic disorder that affects sleep–wake cycles and causes people to fall asleep suddenly, when he inadvertently helped to pave the way towards the latest means of treating insomnia. He discovered that dogs with narcolepsy have a genetic mutation that affects one of two receptors used by the neurotransmitter orexin, the primary role of which was initially thought to be the regulation of appetite. Mignot then found that people with narcolepsy lack orexin, confirming the chemical’s main job: promoting wakefulness. If drugs could be developed to prevent orexin from binding to its receptors, Mignot thought, then people with insomnia would become “narcoleptic for one night”.In 2007, researchers at the pharmaceutical firm Actelion (part of which is now Idorsia Pharmaceuticals in Switzerland) showed that blocking orexin’s two receptors induced sleep in rats, dogs and people. In 2014, the biopharmaceutical company Merck, received US Food and Drug Administration (FDA) approval for the first dual orexin receptor antagonist (DORA) drug, suvorexant (Belsomra). In 2019, another DORA drug — lemborexant (Dayvigo) — was approved, followed, in 2022, by daridorexant (Quviviq).Compared with benzodiazepines and Z-drugs, which inhibit activity all over the brain, DORA drugs affect only the neurons activated by orexins (see ‘Blocking wakefulness’). “The beauty of it is it does nothing but block the stimulation of wakefulness,” says neurologist Joe Herring, who heads neuroscience clinical research at Merck in Rahway, New Jersey. “It’s a physiologically better way to promote sleep.”Alisdair Macdonald/NatureDaridorexant is the only DORA drug for which data are available about daytime functioning, says Antonio Olivieri, chief medical officer at Idorsia, which produces daridorexant. In clinical trials, Idorsia showed that, compared with those given a placebo, people who received daridorexant experienced significant improvements in daytime insomnia symptoms the following day. Data reported in the approvals database of the FDA also indicate that daridorexant has the lowest fatigue and drowsiness scores of the three DORA drugs, possibly because it leaves the body the quickest.So far, there have been no one-to-one comparisons of DORA drugs. “Ideally, you’d have direct evidence of how those drugs compare to each other,” says Daniel Buysse, a sleep scientist at the University of Pittsburgh School of Medicine in Pennsylvania. “But we rarely have such evidence, so instead, we have to rely on statistical techniques that allow you to make indirect comparisons.” It’s also difficult to say definitively how DORA drugs compare with older treatments for insomnia, but Buysse says that drug registration trials suggest that DORA drugs have fewer adverse cognitive or hangover effects compared with benzodiazepines and Z-drugs, as well as less potential for dependence and misuse. The European Insomnia Guideline 2023 placed daridorexant as the next recommended insomnia treatment after CBT-I.The main drawback to DORA drugs, Buysse says, is not medical but financial: their high cost keeps them out of reach of many people who could benefit from them. “There are many patients I would like to prescribe these drugs for, but I know in order for them to get one of these medications we’ll have to go through trials of several other drugs before the request will be considered,” Buysse says. DORA drugs are also available only in a few countries, so far.Given her long history of insomnia, Miranda was given a prescription for suvorexant. Her psychiatrist recommended the drug to her about a year ago. “I was really sceptical that an anti-wakefulness drug would be any different to a pro-sleep drug,” she says. But she quickly felt the difference, and has now come to see the drug as “a saviour”. Without the drug, she says, “I’d probably be on a much higher benzodiazepine dose than I am.” She hopes her suvorexant dose can continue to increase, so that some of her other medications can be reduced.Expanding availabilityOther drugs that target the orexin system are in the clinical pipeline. Seltorexant, for example, is being developed by the US pharmaceutical firm Johnson & Johnson for people with both major depressive disorder and insomnia. Around 70% of people with depression have insomnia, so having a medication that treats both of those disorders “has the potential to fill an important gap”, says Krystal, who has consulted for Johnson & Johnson on the drug. In a phase III trial, participants who took the drug experienced meaningful improvement in both sleep and depressive symptoms, with an antidepressant effect that seemed to be independent of the participants getting better sleep. Seltorexant might have an antidepressant effect because it is designed to block only one of the two types of orexin receptor, Krystal adds, whereas other DORA drugs block both receptor types.Investigations of already-approved DORA drugs are also expanding into other populations. Merck has sponsored investigator-led studies of suvorexant in people with insomnia as well as depression or substance-use disorders, and Idorsia is sponsoring studies of daridorexant’s safety and efficacy in sub-groups of people who have insomnia and other conditions.In 2020, suvorexant became the first medication to be approved for treating sleep disorders in people with Alzheimer’s disease. Insomnia is often a precursor to and co-morbid with Alzheimer’s, and the disease seems to manifest differently in people with the condition. In one study comparing older people with insomnia with those with both insomnia and Alzheimer’s, people with both conditions had a number of extra changes to their sleep patterns, including less time spent in deep sleep — sometimes called slow-wave sleep because that describes the pattern of the brain’s electrical activity during these intervals. Sleep problems in people with Alzheimer’s also seem to have a causal role in increasing levels of toxic substances in the brains of those individuals. Preliminary data suggest that suvorexant could also help to reduce toxic brain proteins. The results of a follow-up study testing that finding are expected in 2026.In the weedsSleeplessness is already among the most common conditions for the medicinal use of the drug cannabis. Miranda, for example, supplements her nightly pharmaceutical regimen with a cannabis tincture that contains a few of the plant’s 100-plus cannabinoids (she lives in a state where cannabis use is legal). “It’s definitely a key player in my sleep-medication arsenal,” she says.Yet, scientifically, little is known about which cannabinoids — if any — promote sleep, and what a safe and effective dose is. “Tens of millions of people around the world are probably using cannabinoids for insomnia, but we have very little good-quality evidence to support that,” says Iain McGregor, director of the Lambert Initiative for Cannabinoid Therapeutics at the University of Sydney in Australia.McGregor is investigating cannabinol (CBN), a molecule that develops in cannabis as the psychoactive component tetrahydrocannabinol (THC) oxidizes. His group reported that CBN increased sleep in rats to a similar degree as zolpidem, but without the drug’s known negative side effect of suppressing rapid-eye-movement sleep. Unpublished data of a single-night trial with 20 people with insomnia disorder show that people fell asleep 7 minutes faster after taking 300 milligrams of CBN compared with those taking a placebo; participants also reported subjective improvements in sleep and mood. Although 7 minutes “doesn’t sound like a lot”, it is on a par with what benzodiazepines and Z-drugs typically accomplish, says Camilla Hoyos, a sleep researcher at the Woolcock Institute of Medical Research in Sydney, who led the work. McGregor, Hoyos and their colleagues are aiming to follow up the work with a large, community-based trial in which people with insomnia take either CBN or a placebo for six weeks at home.As for cannabidiol (CBD) and THC — the most well-known cannabinoids — the prospects for efficacy against insomnia are doubtful, at least for the doses used in trials so far. Several small studies have failed to find a sleep benefit from taking CBD. In one experiment, researchers observed that participants in a study who received 10 milligrams of THC and 200 milligrams of CBD actually slept for 25 minutes less compared with when they received a placebo. Several other company-sponsored trials of low-dose CBD for insomnia were not published, McGregor adds, because they found no significant improvement. “It’s been one failure after the next,” he says.Insomnia’s new frontiersThe search for more effective insomnia treatments continues in other realms, as well. Some research groups are experimenting with different receptors that they hope could lead to new classes of drugs. Gabriella Gobbi, a clinical psychiatrist and research neuroscientist at McGill University in Montreal, Canada, for example, has homed in on one of the brain’s two melatonin receptors, MT2. “We want to find an alternative mechanism without any addiction liability and with fewer side effects, especially for use in children and elderly people,” she says. A molecule that the team developed that binds to MT2 increased the time that rats spent in deep sleep by 30%. Gobbi aims to launch clinical trials in the next two to three years.A few companies and health systems, including the US Department of Veterans Affairs and the Cleveland Clinic in Ohio, have also created or are developing digital platforms for delivering CBT-I. These apps take users through regimens that are tailored to their symptoms. SleepioRx, for example, is a 90-day digital programme that has been evaluated in more than two dozen clinical trials and has showed efficacy as high as 76%. This includes helping people to fall asleep faster, sleep better throughout the night and feel better the next day. In August 2024, the programme, developed by Big Health in San Francisco, California, received FDA clearance. A 2024 meta-analysis of 15 studies that compare in-person and electronically delivered CBT-I concluded that the two approaches were equally effective.Uptake among physicians has been slow so far, Krystal says. But once practitioners catch on, he adds, “I can imagine a world where you have digital care as your first stop, and if that’s not successful, you see a therapist.”Some studies suggest that insomnia can stem from a high level of underlying brain activity during sleep. This raises the question of whether reducing this activity could treat insomnia, says Ruth Benca, a psychiatrist at Wake Forest School of Medicine in North Carolina. Companies and academic research groups are beginning to test this proposition with wearable devices that use auditory tones or mild electrical stimulation to increase slow-wave activity in the brain. Some devices are already on the market, and evidence suggests that they can increase the duration of deep sleep. Last June, for example, researchers at Elemind Technologies in Cambridge, Massachusetts, confirmed that auditory stimuli delivered in sync with specific brain-wave rhythms generated in a headband allowed people who usually struggle for more than 30 minutes to fall asleep to shave an average of 10.5 minutes off that time.In the coming years, according to Benca, researchers hope to learn enough about insomnia’s causes and treatments to be able to recommend personalized therapies based on an individual’s specific demographics, genetics and co-morbidities. These are the frontiers people are working at, she says.Even after a lifetime of struggling to find safe and effective help, Miranda says that she still holds out hope that better treatments for insomnia are on the horizon. “I can’t be on these medications forever,” she says. “They’re going to take years off my life.”
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  • I found a subscription-free smart ring that rivals Oura - and it's $50 off right now

    ZDNET's key takeaways The Ultrahuman Ring Air is the brand's first foray into the smart ring space, and it's available for, no subscription required The ring is great for hardcore fitness enthusiasts and recreational exercisers looking to use their health data to optimize their wellness routines The app's user interface could be improved for easier access to daily logging functions. View now at QVC The Ultrahuman Ring Air is a competitive smart ring that tracks your sleep and fitness. Right now, you can take an additional off the smart ring when you buy it at QVC.Also: Two popular smart rings just got caught copying OuraAs one of the hottest smart rings on the market, the Ultrahuman Ring Air offers features and data collection that goes a step beyond Oura for individuals looking to optimize their health. I tested one alongside the Oura Horizon ring for a month, wearing both around the clock and logging everything from my morning coffee to my late-night cocktails. Suffice it to say, the Ultrahuman ring will excite people dialed into their health and fitness.Also: Oura Ring 3 vs Oura Ring 4: Should you buy the discounted smart ring still on sale or the brand's newest?While Oura seemingly appeals to just about anyone looking to invest in a smart ring, Ultrahuman's offering, while more niche, is arguably better. If the Oura Ring is the girl next door, the Ultrahuman Ring Air is the Silicon Valley-based, Bitcoin-mining neighbor who drinks Soylent. But while it will set hardcore fitness enthusiasts on the right path, this ring will also help anyone, even recreational exercisers, optimize their body to a tee.
    details
    View at QVC Unlike the Oura Ring, which requires a monthly subscription, the Ultrahuman Ring Air is subscription-free. The Ultrahuman comes in matte gray, matte black, silver, and gold. Out of all the smart rings I have tested, it is by far the thinnest, most discreet, and unassuming. Plus, the matte gray finish hasn't scratched or tarnished after a month of use, something I can't say about the other smart rings with shiny metal finishes.From the moment you wake up to the minute you fall asleep, Ultrahuman is sending you notifications on how to make the most of your available energy and body clock. With all these scientific insights into my body, I couldn't help but feel like I was hacking my health -- or playing God. Within an hour of waking, Ultrahuman pings me about my "residual adenosine levels." My what? I had to look it up as well. Adenosine is a naturally occurring chemical associated with wakefulness. It tells me to delay consuming stimulants like caffeine until around two hours after I've been awake to flush adenosine out of my system and boost the impact of caffeine on my energy levels. It also reminds me to expose myself to bright light or exercise during this window if I want an earlier bedtime and wake-up time.Throughout the day, I get pings like this. Ultrahuman tells me when my stimulant permissible window, the window where I can consume caffeine without it disrupting my sleep, is coming to a close. Not only that: Ultrahuman also tells me how much caffeine is in certain stimulants, how long they will stay in my system, and whether they exceed the caffeine intake of my window.As the day goes on, Ultrahuman pings me to stretch my legs and when the ideal bedtime for a sufficient night of sleep would be. All this is calculated based on my wake-up times, sleep, and recovery data. Also: The best smart rings of 2025: Expert tested and reviewedThe Ultrahuman Ring Air measures heart rate, skin temperature, heart rate variability, and resting heart rate to glean data for sleep, recovery, and movement. It also measures VO2 Max, or how the body utilizes oxygen during workouts. Ultrahuman presents all this data in an easy-to-understand format through an app, with scoresfor the big three: sleep, movement, and recovery. For example, when I got a 95 sleep score, it told me I fell asleep faster and stayed asleep for most of my rest duration. In tandem with my high sleep score, I got a 90 recovery score, and the blurb told me that my scores were in great shape, so I "might want to push a little more towards your cognitive and physical fitness goals." On a day when my sleep score was 49 and my recovery score 64, the app instructed me to go on a long walk and try a "non-sleep deep rest session" during the day. Nina Raemont/ZDNETOther health data, like HRV, VO2 Max, and resting heart rate, are tracked and the day-by-day data is aggregated and shown through graphs with daily, weekly, and monthly trends -- depicted with green and red indicators.  All these data points come with explanations of what each indicator means about one's overall health, elucidating the complexity of them.Another health feature the Ultrahuman ring offers is food logging, which leverages ChatGPT-powered AI food insights. I log the food I eat throughout the day, and its Food Optimization AI provides what it calls cyborg insights -- no, really -- about how to avoid glucose spikes when I consume certain foods. When I logged a bag of potato chips, it told me to pair the chips with cheese or other protein, like a hard-boiled egg, to slow down the absorption of glucose. It also told me to drink water before and after eating the chips and take a brisk walk after eating them to lower my glycemic response. While I rarely took this advice, this is a helpful feature for fitness and people who want to optimize their diet and health data.Also: The Oura smart ring's brilliant new features outshine even its titanium finishOf course, you also can log workouts, something I did often while training for my half marathon. The ring doesn't automatically detect that you're exercising, however, if it goes unlogged. I hope Ultrahuman improves this in future updates. I liked that I could see the map of where I ran, my average heart rate, my max heart rate, the calories I burned, and my average pace. Plus, it showed my workout zones, too, something essential for tracking long runs.The last feature that makes this ring ideal for exercise junkies is the Discover tab, which offers video classes for everything from Pilates and weight training to HIIT and yoga. There are also podcasts available for meditation and soundscapes for falling asleep.  Nina Raemont/ZDNETYou can wear the ring for about five days before the battery dies. I tested its battery life compared to Oura's by charging both to 100% on a Tuesday afternoon and waiting to see how long each would last through regular wear and activity. By Sunday morning, the Oura ring was at 7%, and the Ultrahuman Ring Air was at 6%. I will note, however, that the Ultrahuman ring gets hot to the touch after charging.In the next update of the Ultrahuman Ring Air, I'd like to see the app's user interface improve. It could take some notes from Oura's app, which offers sleep, readiness, resilience, and activity on top of a home tab that aggregates this data on the bottom. Ultrahuman's bottom tabs include home, metabolism, zones, Discover, and a bare-bones profile section. I'd also like to see a more accessible logging feature wherein you don't have to scroll all the way down the app to use for food, exercise tracking, weight, and more.ZDNET's buying adviceWho should buy this ring? I can imagine that anybody who's dialed into fitness and health metrics will get full use of the Ultrahuman Ring Air. And given how often my sleep duration and sleep and recovery scores from the Ultrahuman mimicked that of Oura's, I wouldn't be afraid to call this a subscription-free Oura dupe with rivaling data and battery life.   Ultimately, the Ultrahuman Ring Air impressed me. It's exciting to see such a new product step up to be a competitive fitness smart ring, being just niche enough to carve out an audience of devout fitness freaks but with data presentation, health metrics, and AI suggestions that could cater to the average Joe just as well.When will this deal expire? This deal will expire on May 19. The deal runs for four days. We're sorry if you've missed out on this deal, but don't fret -- we're constantly finding new chances to save and sharing them with you at ZDNET.comFeatured reviews
    #found #subscriptionfree #smart #ring #that
    I found a subscription-free smart ring that rivals Oura - and it's $50 off right now
    ZDNET's key takeaways The Ultrahuman Ring Air is the brand's first foray into the smart ring space, and it's available for, no subscription required The ring is great for hardcore fitness enthusiasts and recreational exercisers looking to use their health data to optimize their wellness routines The app's user interface could be improved for easier access to daily logging functions. View now at QVC The Ultrahuman Ring Air is a competitive smart ring that tracks your sleep and fitness. Right now, you can take an additional off the smart ring when you buy it at QVC.Also: Two popular smart rings just got caught copying OuraAs one of the hottest smart rings on the market, the Ultrahuman Ring Air offers features and data collection that goes a step beyond Oura for individuals looking to optimize their health. I tested one alongside the Oura Horizon ring for a month, wearing both around the clock and logging everything from my morning coffee to my late-night cocktails. Suffice it to say, the Ultrahuman ring will excite people dialed into their health and fitness.Also: Oura Ring 3 vs Oura Ring 4: Should you buy the discounted smart ring still on sale or the brand's newest?While Oura seemingly appeals to just about anyone looking to invest in a smart ring, Ultrahuman's offering, while more niche, is arguably better. If the Oura Ring is the girl next door, the Ultrahuman Ring Air is the Silicon Valley-based, Bitcoin-mining neighbor who drinks Soylent. But while it will set hardcore fitness enthusiasts on the right path, this ring will also help anyone, even recreational exercisers, optimize their body to a tee. details View at QVC Unlike the Oura Ring, which requires a monthly subscription, the Ultrahuman Ring Air is subscription-free. The Ultrahuman comes in matte gray, matte black, silver, and gold. Out of all the smart rings I have tested, it is by far the thinnest, most discreet, and unassuming. Plus, the matte gray finish hasn't scratched or tarnished after a month of use, something I can't say about the other smart rings with shiny metal finishes.From the moment you wake up to the minute you fall asleep, Ultrahuman is sending you notifications on how to make the most of your available energy and body clock. With all these scientific insights into my body, I couldn't help but feel like I was hacking my health -- or playing God. Within an hour of waking, Ultrahuman pings me about my "residual adenosine levels." My what? I had to look it up as well. Adenosine is a naturally occurring chemical associated with wakefulness. It tells me to delay consuming stimulants like caffeine until around two hours after I've been awake to flush adenosine out of my system and boost the impact of caffeine on my energy levels. It also reminds me to expose myself to bright light or exercise during this window if I want an earlier bedtime and wake-up time.Throughout the day, I get pings like this. Ultrahuman tells me when my stimulant permissible window, the window where I can consume caffeine without it disrupting my sleep, is coming to a close. Not only that: Ultrahuman also tells me how much caffeine is in certain stimulants, how long they will stay in my system, and whether they exceed the caffeine intake of my window.As the day goes on, Ultrahuman pings me to stretch my legs and when the ideal bedtime for a sufficient night of sleep would be. All this is calculated based on my wake-up times, sleep, and recovery data. Also: The best smart rings of 2025: Expert tested and reviewedThe Ultrahuman Ring Air measures heart rate, skin temperature, heart rate variability, and resting heart rate to glean data for sleep, recovery, and movement. It also measures VO2 Max, or how the body utilizes oxygen during workouts. Ultrahuman presents all this data in an easy-to-understand format through an app, with scoresfor the big three: sleep, movement, and recovery. For example, when I got a 95 sleep score, it told me I fell asleep faster and stayed asleep for most of my rest duration. In tandem with my high sleep score, I got a 90 recovery score, and the blurb told me that my scores were in great shape, so I "might want to push a little more towards your cognitive and physical fitness goals." On a day when my sleep score was 49 and my recovery score 64, the app instructed me to go on a long walk and try a "non-sleep deep rest session" during the day. Nina Raemont/ZDNETOther health data, like HRV, VO2 Max, and resting heart rate, are tracked and the day-by-day data is aggregated and shown through graphs with daily, weekly, and monthly trends -- depicted with green and red indicators.  All these data points come with explanations of what each indicator means about one's overall health, elucidating the complexity of them.Another health feature the Ultrahuman ring offers is food logging, which leverages ChatGPT-powered AI food insights. I log the food I eat throughout the day, and its Food Optimization AI provides what it calls cyborg insights -- no, really -- about how to avoid glucose spikes when I consume certain foods. When I logged a bag of potato chips, it told me to pair the chips with cheese or other protein, like a hard-boiled egg, to slow down the absorption of glucose. It also told me to drink water before and after eating the chips and take a brisk walk after eating them to lower my glycemic response. While I rarely took this advice, this is a helpful feature for fitness and people who want to optimize their diet and health data.Also: The Oura smart ring's brilliant new features outshine even its titanium finishOf course, you also can log workouts, something I did often while training for my half marathon. The ring doesn't automatically detect that you're exercising, however, if it goes unlogged. I hope Ultrahuman improves this in future updates. I liked that I could see the map of where I ran, my average heart rate, my max heart rate, the calories I burned, and my average pace. Plus, it showed my workout zones, too, something essential for tracking long runs.The last feature that makes this ring ideal for exercise junkies is the Discover tab, which offers video classes for everything from Pilates and weight training to HIIT and yoga. There are also podcasts available for meditation and soundscapes for falling asleep.  Nina Raemont/ZDNETYou can wear the ring for about five days before the battery dies. I tested its battery life compared to Oura's by charging both to 100% on a Tuesday afternoon and waiting to see how long each would last through regular wear and activity. By Sunday morning, the Oura ring was at 7%, and the Ultrahuman Ring Air was at 6%. I will note, however, that the Ultrahuman ring gets hot to the touch after charging.In the next update of the Ultrahuman Ring Air, I'd like to see the app's user interface improve. It could take some notes from Oura's app, which offers sleep, readiness, resilience, and activity on top of a home tab that aggregates this data on the bottom. Ultrahuman's bottom tabs include home, metabolism, zones, Discover, and a bare-bones profile section. I'd also like to see a more accessible logging feature wherein you don't have to scroll all the way down the app to use for food, exercise tracking, weight, and more.ZDNET's buying adviceWho should buy this ring? I can imagine that anybody who's dialed into fitness and health metrics will get full use of the Ultrahuman Ring Air. And given how often my sleep duration and sleep and recovery scores from the Ultrahuman mimicked that of Oura's, I wouldn't be afraid to call this a subscription-free Oura dupe with rivaling data and battery life.   Ultimately, the Ultrahuman Ring Air impressed me. It's exciting to see such a new product step up to be a competitive fitness smart ring, being just niche enough to carve out an audience of devout fitness freaks but with data presentation, health metrics, and AI suggestions that could cater to the average Joe just as well.When will this deal expire? This deal will expire on May 19. The deal runs for four days. We're sorry if you've missed out on this deal, but don't fret -- we're constantly finding new chances to save and sharing them with you at ZDNET.comFeatured reviews #found #subscriptionfree #smart #ring #that
    WWW.ZDNET.COM
    I found a subscription-free smart ring that rivals Oura - and it's $50 off right now
    ZDNET's key takeaways The Ultrahuman Ring Air is the brand's first foray into the smart ring space, and it's available for $349 (though it's currently $50 off at QVC), no subscription required The ring is great for hardcore fitness enthusiasts and recreational exercisers looking to use their health data to optimize their wellness routines The app's user interface could be improved for easier access to daily logging functions. View now at QVC The Ultrahuman Ring Air is a competitive smart ring that tracks your sleep and fitness. Right now, you can take an additional $50 off the smart ring when you buy it at QVC.Also: Two popular smart rings just got caught copying OuraAs one of the hottest smart rings on the market, the Ultrahuman Ring Air offers features and data collection that goes a step beyond Oura for individuals looking to optimize their health. I tested one alongside the Oura Horizon ring for a month, wearing both around the clock and logging everything from my morning coffee to my late-night cocktails. Suffice it to say, the Ultrahuman ring will excite people dialed into their health and fitness.Also: Oura Ring 3 vs Oura Ring 4: Should you buy the discounted smart ring still on sale or the brand's newest?While Oura seemingly appeals to just about anyone looking to invest in a smart ring, Ultrahuman's offering, while more niche, is arguably better. If the Oura Ring is the girl next door, the Ultrahuman Ring Air is the Silicon Valley-based, Bitcoin-mining neighbor who drinks Soylent. But while it will set hardcore fitness enthusiasts on the right path, this ring will also help anyone, even recreational exercisers, optimize their body to a tee. details View at QVC Unlike the Oura Ring, which requires a $6 monthly subscription, the Ultrahuman Ring Air is subscription-free. The Ultrahuman comes in matte gray, matte black, silver, and gold. Out of all the smart rings I have tested, it is by far the thinnest, most discreet, and unassuming. Plus, the matte gray finish hasn't scratched or tarnished after a month of use, something I can't say about the other smart rings with shiny metal finishes.From the moment you wake up to the minute you fall asleep, Ultrahuman is sending you notifications on how to make the most of your available energy and body clock. With all these scientific insights into my body, I couldn't help but feel like I was hacking my health -- or playing God. Within an hour of waking, Ultrahuman pings me about my "residual adenosine levels." My what? I had to look it up as well. Adenosine is a naturally occurring chemical associated with wakefulness. It tells me to delay consuming stimulants like caffeine until around two hours after I've been awake to flush adenosine out of my system and boost the impact of caffeine on my energy levels. It also reminds me to expose myself to bright light or exercise during this window if I want an earlier bedtime and wake-up time.Throughout the day, I get pings like this. Ultrahuman tells me when my stimulant permissible window, the window where I can consume caffeine without it disrupting my sleep, is coming to a close. Not only that: Ultrahuman also tells me how much caffeine is in certain stimulants, how long they will stay in my system, and whether they exceed the caffeine intake of my window.As the day goes on, Ultrahuman pings me to stretch my legs and when the ideal bedtime for a sufficient night of sleep would be. All this is calculated based on my wake-up times, sleep, and recovery data. Also: The best smart rings of 2025: Expert tested and reviewedThe Ultrahuman Ring Air measures heart rate, skin temperature, heart rate variability (HRV), and resting heart rate to glean data for sleep, recovery, and movement. It also measures VO2 Max, or how the body utilizes oxygen during workouts. Ultrahuman presents all this data in an easy-to-understand format through an app, with scores (and explanations) for the big three: sleep, movement, and recovery. For example, when I got a 95 sleep score, it told me I fell asleep faster and stayed asleep for most of my rest duration. In tandem with my high sleep score, I got a 90 recovery score, and the blurb told me that my scores were in great shape, so I "might want to push a little more towards your cognitive and physical fitness goals." On a day when my sleep score was 49 and my recovery score 64, the app instructed me to go on a long walk and try a "non-sleep deep rest session" during the day. Nina Raemont/ZDNETOther health data, like HRV, VO2 Max, and resting heart rate, are tracked and the day-by-day data is aggregated and shown through graphs with daily, weekly, and monthly trends -- depicted with green and red indicators.  All these data points come with explanations of what each indicator means about one's overall health, elucidating the complexity of them.Another health feature the Ultrahuman ring offers is food logging, which leverages ChatGPT-powered AI food insights. I log the food I eat throughout the day, and its Food Optimization AI provides what it calls cyborg insights -- no, really -- about how to avoid glucose spikes when I consume certain foods. When I logged a bag of potato chips, it told me to pair the chips with cheese or other protein, like a hard-boiled egg, to slow down the absorption of glucose. It also told me to drink water before and after eating the chips and take a brisk walk after eating them to lower my glycemic response. While I rarely took this advice, this is a helpful feature for fitness and people who want to optimize their diet and health data.Also: The Oura smart ring's brilliant new features outshine even its titanium finishOf course, you also can log workouts, something I did often while training for my half marathon. The ring doesn't automatically detect that you're exercising, however, if it goes unlogged. I hope Ultrahuman improves this in future updates. I liked that I could see the map of where I ran, my average heart rate, my max heart rate, the calories I burned, and my average pace. Plus, it showed my workout zones, too, something essential for tracking long runs.The last feature that makes this ring ideal for exercise junkies is the Discover tab, which offers video classes for everything from Pilates and weight training to HIIT and yoga. There are also podcasts available for meditation and soundscapes for falling asleep.  Nina Raemont/ZDNETYou can wear the ring for about five days before the battery dies. I tested its battery life compared to Oura's by charging both to 100% on a Tuesday afternoon and waiting to see how long each would last through regular wear and activity. By Sunday morning, the Oura ring was at 7%, and the Ultrahuman Ring Air was at 6%. I will note, however, that the Ultrahuman ring gets hot to the touch after charging.In the next update of the Ultrahuman Ring Air, I'd like to see the app's user interface improve. It could take some notes from Oura's app, which offers sleep, readiness, resilience, and activity on top of a home tab that aggregates this data on the bottom. Ultrahuman's bottom tabs include home, metabolism, zones, Discover, and a bare-bones profile section. I'd also like to see a more accessible logging feature wherein you don't have to scroll all the way down the app to use for food, exercise tracking, weight, and more.ZDNET's buying adviceWho should buy this ring? I can imagine that anybody who's dialed into fitness and health metrics will get full use of the Ultrahuman Ring Air. And given how often my sleep duration and sleep and recovery scores from the Ultrahuman mimicked that of Oura's, I wouldn't be afraid to call this a subscription-free Oura dupe with rivaling data and battery life.   Ultimately, the Ultrahuman Ring Air impressed me. It's exciting to see such a new product step up to be a competitive fitness smart ring, being just niche enough to carve out an audience of devout fitness freaks but with data presentation, health metrics, and AI suggestions that could cater to the average Joe just as well.When will this deal expire? This deal will expire on May 19. The deal runs for four days. We're sorry if you've missed out on this deal, but don't fret -- we're constantly finding new chances to save and sharing them with you at ZDNET.comFeatured reviews
    0 Yorumlar 0 hisse senetleri 0 önizleme
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