The most notable new sleep medication of 2023 was Lumryz, an extended-release form of sodium oxybate approved by the FDA in May 2023 for narcolepsy. Meanwhile, a newer class of insomnia drugs called dual orexin receptor antagonists (DORAs) continued gaining traction as alternatives to older sleep aids, and an experimental drug in clinical trials showed dramatic results that could reshape narcolepsy treatment in the years ahead.
Lumryz: The Major 2023 Approval
Lumryz received FDA approval in May 2023 for treating two hallmark symptoms of narcolepsy: cataplexy (sudden muscle weakness triggered by emotions) and excessive daytime sleepiness. Its active ingredient, sodium oxybate, has been available since 2002, but Lumryz introduced a significant change in how it’s taken. Older versions required patients to wake up in the middle of the night to take a second dose. Lumryz is an extended-release formulation taken just once at bedtime.
That difference matters more than it might sound. In a clinical study called RESTORE, about 69% of patients on the older twice-nightly version reported missing their second dose at least once, and 80% of those who missed it felt worse the next day. Roughly 30% of patients reported anxiety about having to wake up for that second dose. After switching to once-nightly Lumryz, over 91% said they were better able to follow their medication schedule. These findings align with broader research showing that once-daily dosing leads to significantly better adherence than regimens requiring multiple doses.
Sodium oxybate works by activating GABA-B receptors in the brain, which deepens sleep by increasing time spent in the more restorative stages of sleep and reducing fragmented wakefulness. Patients typically start at 4.5 grams per night, with the dose gradually increased over several weeks up to a maximum of 9 grams based on how well it works and how well it’s tolerated. In October 2024, the FDA expanded Lumryz’s approval to include patients as young as 7 years old.
Orexin Receptor Antagonists for Insomnia
While Lumryz targets narcolepsy, the biggest shift in insomnia treatment over the past few years has come from dual orexin receptor antagonists, or DORAs. These drugs work by blocking orexin, a brain chemical that promotes wakefulness. Rather than sedating the brain the way older sleep drugs do, DORAs essentially turn down the “wake signal,” allowing sleep to happen more naturally.
Three DORAs are now on the market: suvorexant (Belsomra, approved 2014), lemborexant (Dayvigo, approved 2019), and daridorexant (Quviviq, approved January 2022). Quviviq was the newest of the three heading into 2023 and was still gaining wider availability and insurance coverage during that year. All three are effective at helping people fall asleep faster and stay asleep longer, with performance comparable to older drugs like extended-release zolpidem on key sleep measures.
Where DORAs stand out is safety. Older sleep medications, including benzodiazepines and Z-drugs like zolpidem, zaleplon, and eszopiclone, carry risks of dependence even in people who take them as prescribed. Long-term use can lead to withdrawal symptoms when stopping. The FDA has also required Z-drugs to carry warnings about complex sleep behaviors, including sleepwalking, sleep-driving, and other dangerous activities people don’t remember the next morning. DORAs are generally unlikely to cause dependence or the tolerance buildup that makes older drugs less effective over time. Multiple analyses have found that DORAs offer at least equivalent effectiveness with a better safety profile than traditional sleep medications.
How Insurance Covers Newer Sleep Drugs
Access to these newer medications can be complicated. Most insurers, including major plans like Aetna, require prior authorization before covering DORAs like Quviviq, Dayvigo, or Belsomra. In practice, this means your doctor needs to document that you’ve already tried and either didn’t respond to or couldn’t tolerate a generic option, such as zolpidem or a benzodiazepine. The main exception is patients 65 and older, who may get approval without first trying older drugs, likely because benzodiazepines and Z-drugs pose higher fall and cognitive risks in older adults. Insurers also typically require documentation that other factors contributing to poor sleep, like sleep hygiene issues or untreated medical conditions, have been addressed.
An Experimental Drug Targeting the Root Cause
Perhaps the most exciting development in 2023’s sleep medicine pipeline was oveporexton (TAK-861), an experimental drug that takes the opposite approach of insomnia DORAs. While DORAs block the wake-promoting orexin system to help people sleep, oveporexton activates it, directly replacing the orexin signaling that people with narcolepsy type 1 have lost. Narcolepsy type 1 is caused by the destruction of orexin-producing neurons in the brain, so this drug targets the root cause rather than managing symptoms indirectly.
In a phase 2 trial published in the New England Journal of Medicine, oveporexton produced striking results. Participants who took the drug stayed awake dramatically longer on standard wakefulness tests, with improvements of up to 25 minutes compared to a 1.2-minute decline in the placebo group. Sleepiness scores dropped by as much as 13.8 points on a standard 24-point scale, compared to 2.5 points with placebo. Cataplexy episodes also decreased. The most common side effects were insomnia (which resolved within about a week for most participants), urinary urgency, and urinary frequency. No liver toxicity was observed.
Oveporexton is not yet available by prescription and still needs to complete later-stage trials, but its approach represents a fundamentally different strategy: restoring what the brain is missing rather than compensating with sedation or symptom management.
How Newer Options Compare to Older Sleep Aids
For people with insomnia, the practical question is whether newer drugs are worth pursuing over familiar generics. Head-to-head comparisons show that lemborexant at 10 mg is slightly better than extended-release zolpidem at reducing the time it takes to fall asleep and the amount of time spent awake in the middle of the night, though these differences level off after about four weeks. Both DORAs and Z-drugs have a “number needed to treat” (the number of patients who need to take the drug for one to benefit) of fewer than 10, meaning both classes work for a meaningful proportion of people who try them.
The real distinction comes down to long-term use. Z-drugs and benzodiazepines cause dependence at similar rates, and stopping them after extended use can trigger rebound insomnia and withdrawal. DORAs do not appear to create this cycle. For someone who needs ongoing help with sleep rather than a short-term fix, that difference in dependency risk is significant. All sleep medications, newer ones included, can still cause next-morning drowsiness and impair driving ability, so that trade-off doesn’t disappear with the newer drug class.