Sleep disorders affect an estimated 50-70 million Americans and are linked to cardiovascular disease, cognitive impairment, metabolic dysfunction, and increased accident risk.

Yet despite established therapies for conditions such as insomnia, obstructive sleep apnea (OSA), restless legs syndrome (RLS), and narcolepsy, available treatments often have significant limitations.

Now, sleep experts say the therapeutic landscape may be changing.

“I think we’re entering the golden age of sleep in terms of treatment options,” Charlene Gamaldo, MD, professor of neurology at Johns Hopkins Medicine in Baltimore, told Medscape Medical News. “Just in the last 5-7 years, we’ve been seeing all these new medications and new classes [of drugs].”

This growing wave of next-generation treatments — ranging from orexin-targeting drugs to oral agents and wearable neuromodulation devices — is beginning to reshape how physicians approach sleep disorders.

Where Current Therapies Fall Short

Although evidence-based treatments exist for most sleep disorders, challenges with access, tolerability, adherence, or incomplete symptom control can hinder their efficacy.

Cognitive behavioral therapy for insomnia (CBT-I) remains first-line but is constrained by a shortage of trained providers, leaving many patients reliant on traditional hypnotics — including benzodiazepines and nonbenzodiazepine “Z-drugs” — that carry risks for dependence, falls, and cognitive impairment.

Continuous positive airway pressure (CPAP) is highly effective for OSA when used consistently, yet long-term adherence can be difficult for some patients. Dopamine agonists for RLS are associated with augmentation over time — a medication-induced worsening characterized by earlier symptom onset, increased severity, or spread to other body regions — and current narcolepsy therapies largely address downstream symptoms rather than the underlying orexin deficiency.

Collectively, these limitations have intensified efforts to develop therapies that are safer, more durable, and better aligned with sleep neurobiology, with the goal of improving real-world outcomes across these disorders.

However, the first step toward better treatment depends on an accurate diagnosis, said Michael Perlis, PhD, associate professor of psychiatry and director of the Behavioral Sleep Medicine Program at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perlis has been involved in the development of the Sleep Health Screener, an initiative designed to improve recognition of sleep disorders through structured patient self-assessment.

More than a dozen distinct sleep disorders exist, and they frequently overlap, he noted. Rather than relying solely on clinicians to initiate evaluation, he is an advocate for placing screening tools directly in patients’ hands and encouraging structured self-assessment.

Insomnia: From Z-Drugs to Dual-Orexin Receptor Antagonists (DORAs)

The most common sleep disorder, insomnia, affects an estimated 10% of adults in the US in its chronic form, with an additional 20% reporting intermittent symptoms.

CBT-I remains the gold standard for chronic insomnia, with a response rate of about 70% — which is “as good, or better, than most nonpharmacologic therapeutics and is on par with, or better than, many medical interventions,” said Perlis.

The challenge, he noted, is the limited availability of trained CBT-I providers, with only about 825 clinicians listed in the International CBT-I Provider Directory.

For those who cannot find a therapist, the prescription-only digital therapeutic app SleepioRx was cleared by the FDA in 2024 and “offers an accessible, evidence-based CBT-I option,” said Alex Dimitriu, MD, a psychiatrist and sleep medicine physician at Menlo Park Psychiatry and Sleep Medicine in Menlo Park, California.

The other important development in insomnia treatment in recent years is DORAs, starting with the approval of suvorexant (Belsomra) in 2014, followed by lemborexant (Dayvigo) in 2019 and daridorexant (Quviviq) in 2022.

These medications work by blocking orexin, “the neurotransmitter that coordinates all the other wake transmitters,” Gamaldo said.

Although DORAs have been available for several years, Gamaldo said she “still finds it very exciting because they have continued to demonstrate that they’re probably not habit-forming and don’t have rebound insomnia.”

In contrast, Z-drugs — which have long been used for insomnia and include zolpidem, eszopiclone, and zaleplon — have been associated with dependence, falls, fractures, and potential cognitive effects, particularly in older adults.

DORAs have been evaluated specifically for safety in older adults and have demonstrated favorable tolerability, Gamaldo said. A recent systematic review showed that all three currently FDA-approved DORAs are effective for insomnia.

Additional agents are in development, including a shorter-acting DORA, vornorexant, designed to reduce next-day grogginess, which performed well in a recent phase 3 trial.

RLS: From Drugs to Devices

Estimates show that RLS affects an estimated 8% of adults in the US, with about 3% experiencing frequent moderate or severe symptoms.

New treatments for RLS are evolving, driven in part by concerns about augmentation and long-term tolerability with dopamine agonists.

One novel and relatively new treatment for moderate-to-severe, medication-refractory RLS is the NTX100 Tonic Motor Activation (TOMAC) System — a wearable, FDA-cleared peroneal nerve stimulation device that is covered by Medicare and designed to reduce symptoms and improve sleep quality.

Gamaldo noted that the device provides a nonpharmacologic alternative without medication-related side effects and has shown promising results, including among patients who are refractory to standard treatment.

Evidence supporting the device remains moderate, likely due to its relatively recent introduction, Gamaldo said, adding that its role in treatment will likely expand as more data become available.

OSA: Moving Beyond CPAP

CPAP remains the first-line treatment for OSA, which affects roughly 1 in 3 adults in the US. OSA is characterized by repetitive upper airway obstruction during sleep, resulting in intermittent hypoxia, arousals, and fragmented rest.

Despite the common perception that many patients are unable to tolerate CPAP, a growing body of data suggest that the vast majority are able to adhere to the treatment, said Atul Malhotra, MD, a sleep medicine specialist and professor of medicine at the University of California, San Diego.

However, for those who cannot, there are other, newer treatment options. One of those is hypoglossal nerve stimulation, which involves implanting a device that uses electrical stimulation to push the tongue forward during sleep, Malhotra explained.

The first of these devices was approved in 2014 following results from an uncontrolled cohort study. However, the population in that observational trial was relatively homogenous and had an average BMI in the healthy range, even though many people with OSA have obesity.

Since then, additional devices have been investigated, including one using proximal, instead of distal, hypoglossal nerve stimulation. Malhotra recently presented data on that device from the randomized controlled OSPREY trial at the 2025 meeting of the American College of Chest Physicians.

The study population included diverse participants with moderate-to-severe OSA who had an average BMI of 30.6. The response rate was 65% after 1 year of treatment.

Since it involves an invasive procedure, there is a small risk for bleeding, infection, and initial local irritation or pain. Its primary advantage over CPAP is better adherence, Malhotra said. However, the device has not yet been approved by the FDA.

In 2024, the FDA approved the first medication indicated for OSA, the GLP-1 and glucose-dependent insulinotropic polypeptide dual agonist tirzepatide, for adults with obesity and OSA. The approval was based on results from the SURMOUNT-OSA trial, which was led by Malhotra.

While the weight loss that results from tirzepatide definitely helps with OSA, researchers suspect the drug works on another mechanism of OSA that isn’t yet fully understood.

“The majority of the effect can be attributable to weight loss, but some of the improvements we saw we think maybe related to other factors,” Malhotra said.

In addition, an investigational oral agent, IHL-42X, has entered phase 3 trials for the treatment of OSA, combining two drugs with distinct mechanisms of action. One, acetazolamide, improves upper airway muscle tone, while the other, dronabinol, acts on cannabinoid receptors. The combination drug was associated with reductions of up to 83% in the apnea-hypopnea index.

The investigational oral drug AD109, a combination of aroxybutynin and atomoxetine, showed positive results in two phase 3 trials. “This is a very welcome addition to the sleep apnea space and offers hope of an oral pill for sleep apnea,” Dimitriu said.

Narcolepsy: Addressing the Orexin Deficit

Narcolepsy is a relatively rare disorder, affecting an estimated 30-80 per 100,000 people in the US. It is characterized by excessive daytime sleepiness and, in type 1 disease, cataplexy. Unlike insomnia, which involves hyperarousal, narcolepsy is associated with a deficiency of orexin, a neuropeptide that stabilizes wakefulness.

That biology has driven the development of orexin 2 receptor (OX2R) agonists designed to restore wake-promoting signaling. Rather than blocking orexin receptors to induce sleep, as in insomnia, these agents bind to the receptor to promote wakefulness.

While no OX2R agonists have been approved in the US, phase 3 data on one agent for narcolepsy type 1, was presented at the World Sleep conference in September with findings that looked “quite impressive,” Gamaldo said.

On February 10, the FDA accepted the NDA for the drug according to a release from the drug’s manufacturer, Takeda.

In November, results from a phase 2 study of alixorexton in narcolepsy type 2 showed promising results. The drug is now advancing to phase 3 trials.

“These new orexin agonists that are still in the pipeline look very promising in terms of the magnitude of the improvement in sleepiness,” Malhotra said. “It’s sort of jaw-dropping when you look at how much it improves, and while the older [OX2R agonist] drugs had some hepatoxicity, the newer drugs seem to have sorted that out.”

Dimitriu, added that “orexin agonists like TAK-861 [oveporexton] are the closest we’ve come to a functional treatment for narcolepsy.”

As research continues, Gamaldo suggested that modulation of the orexin system could potentially extend beyond narcolepsy to other sleep disorders, including circadian rhythm conditions.

“It has some autonomic elements to it, so that’s why exploring this pathway from a pharmacotherapeutic standpoint is kind of exciting,” she said. “How many birds could we maybe be hitting with this stone?”

Gamaldo reported consulting for Incannex, Jazz, and Takeda. Malhotra reported consulting for Eli Lilly, LivaNova, Sunrise, ZOLL, and Powell Mansfield and co-founded and has equity in Clairyon. Perlis and Dimitriu reported having no disclosures.

Tara Haelle is a science and health journalist based in Dallas.