Orexin-blocking insomnia drugs were not linked to more falls or fractures across 19 studies

Sleeping pills have long carried a known downside for older adults: a higher chance of falling. As the authors of a new review put it, falls are the leading cause of injury in older adults, and sedative-hypnotic use is a known risk factor.

A newer class of insomnia medicines works differently. Dual orexin receptor antagonists, known as DORAs, block orexin, a brain chemical that helps keep people awake, instead of broadly sedating the brain. A systematic review in the Journal of the American Geriatrics Society pooled 19 studies and found no sign that these drugs raise the risk of falls or fractures. The authors caution that the evidence in older adults is thin.

Why falls matter for insomnia drug choices

Chronic insomnia is common among older adults, and a 2026 review in SLEEP describes its treatment in that group as particularly hard because of changes in sleep with age, multiple health conditions and a greater sensitivity to side effects of medicines. Falls are where those side effects matter most.

The older sleeping pills carry that risk. The Z-drugs, such as zolpidem and zopiclone, were introduced as safer alternatives to benzodiazepines. A 2017 meta-analysis in Age and Ageing of 14 studies found that Z-drugs are associated with an increased risk for fractures, about 63% higher odds, with a possible increase in falls and injuries as well. Those studies were observational, so people who take sleeping pills may differ in other ways.

That overlap is why sleep medicines get close attention in older people. The American Geriatrics Society’s Beers Criteria, updated in 2023, is an explicit list of medicines that are typically best avoided by older adults in most circumstances. A sleep medicine that did not add to fall risk would fill a real gap.

How the orexin insomnia drug review worked

The researchers searched three medical databases up to August 2025 for studies that reported falls or fractures in people taking DORAs and in people not taking them. They included both randomized trials and observational studies, from any clinical setting, and two reviewers screened the studies and pulled out the data independently.

They found 19 studies with 183,595 participants: 10 randomized controlled trials and 9 observational studies. They also calculated what is known as the optimal information size, the minimum number of events needed to detect a clinically meaningful effect. That figure shows whether a pooled analysis has enough falls and fractures in it to give a reliable answer.

What the review found for falls and fractures

Across all 19 studies, DORA use did not increase the risk of falls compared with not using the drugs. In the randomized trials alone, falls were less common among people taking DORAs, but the observational studies did not show that reduction. No association was observed between DORAs and fractures.

The authors conclude that DORAs do not appear to increase the risk of falls or fractures in adults, and that the drugs may be safer alternatives to traditional insomnia medicines.

Why the insomnia drug findings need caution

The authors attach clear caveats. Falls and fractures were uncommon in the studies, so there were few events to compare. The pooled data fell short of the optimal information size, meaning there were not enough events to reliably detect a meaningful difference. And there were limited data in older adults, the group most at risk from falls and most in need of an answer.

The randomized trial result, fewer falls with DORAs, rests on even fewer events and was not matched in the observational data, so it is a hint and nothing more. Trials also tend to enroll healthier people than those who take sleep medicines in everyday life.

How orexin drugs fit into insomnia treatment

The American Academy of Sleep Medicine (AASM) 2017 guideline on drug treatment for chronic insomnia suggests that clinicians use suvorexant as a treatment for sleep maintenance insomnia, the kind where people wake during the night, in adults. The recommendation is weak, and the guideline gives similar weak recommendations for several older drugs. It also says it should be used in conjunction with other AASM guidelines on evaluating and treating insomnia.

Medicines are not the first step in most guidance. The American College of Physicians’ 2016 guideline recommends that all adult patients receive cognitive behavioral therapy for insomnia (CBT-I), a structured form of talking therapy aimed at sleep habits and thoughts about sleep, as the first treatment for chronic insomnia. It advises a shared decision about adding medicines, including their benefits, harms and costs, when CBT-I alone has not worked.

For the orexin-blocking drugs themselves, the 2026 SLEEP review pooled trials in older adults with chronic insomnia. Compared with placebo, the drugs helped people fall asleep faster, stay asleep longer and sleep more in total over one to three months. Lemborexant and suvorexant had more side effects than placebo, though not more serious ones, and the authors noted that the evidence in older adults remains limited.

What the orexin drug review cannot tell us

The review compared people taking DORAs with people not taking them. It did not compare DORAs directly with older sleeping pills, so it cannot say how much safer they are than those drugs. Falls and fractures were its only pooled outcomes, and the findings apply to the doses and settings in the included studies, where relatively few participants were older adults.

What this adds to insomnia drug safety

For a class of drugs that has been described as potentially safer, the review offers early reassurance that DORAs are not linked to more falls or fractures overall. It does not settle the question for the people most at risk, older adults, because too few of them were studied.

The findings do not change any guidance. The authors call for further research, particularly in older adults, to confirm whether the reassuring pattern holds.