A 40-week study found that the insomnia treatment daridorexant, taken every night for up to 12 months, was well tolerated with no signs of tolerance (loss of effect) or physical dependence.

Daridorexant is a dual orexin receptor antagonist, which blocks the binding of the wake-promoting neuropeptides orexins. It is thought to decrease the wake drive, allowing sleep to occur without altering the proportion of sleep stages. After discontinuing treatment, the study also found no evidence of withdrawal or rebound insomnia.

The results were published in the journal CNS Drugs.

“It is interesting to see how different the mechanism of dual orexin receptor antagonism works for patients with insomnia disorder,” says lead author Dieter Kunz, MD, of the Clinic for Sleep and Chronomedicine, St. Hedwig-Krankenhaus Berlin, in a release. “Rather than inducing sleep through broad inhibition of the brain, the over-active wakefulness causing their insomnia is gradually brought under control with nightly administration of daridorexant.” 

The phase 3 international, randomized, double-blind, parallel-group, placebo-controlled extension study was designed to evaluate the long-term use of daridorexant in patients with insomnia disorder who had completed one of the two pivotal 12-week phase 3 studies

The primary objective was to assess the long-term safety and tolerability of daridorexant. Exploratory objectives were to evaluate the efficacy of daridorexant on sleep and daytime functioning. 

In total, 804 adults with insomnia disorder who completed the 12-week studies were included in this extension study. Patients originally randomized to daridorexant 10 mg, 25 mg, or 50 mg remained on their respective treatments. Patients randomized to placebo were re-randomized to either daridorexant 25 mg or placebo. A 7-day placebo run-out followed the 40-week treatment period.

For people with insomnia who require sleep medication, few drugs are approved for long-term use. Daridorexant has now been shown in two clinical studies to improve nighttime sleep and patients’ ability to function during the day while avoiding major safety concerns, according to the study.

“The improvement in sleep onset, sleep maintenance, and daytime functioning seen with 50 mg daridorexant were sustained for up to 12 months,” says Kunz. “Importantly, as we publish in this manuscript, long-term treatment with daridorexant was not associated with any tolerance or physical dependence, neither did we see withdrawal symptoms nor rebound insomnia upon cessation of administration.”

The overall incidence of treatment-emergent adverse events was similar across groups (35%-40%). The most commonly reported one during double-blind treatment in all groups was nasopharyngitis. Falls, headaches, and somnolence were reported in about 3% of patients, with dizziness and fatigue in about 2% of patients in any group.

Improvements in sleep and daytime functioning were maintained through the end of the treatment and were most pronounced with a 50 mg dosage. 

The authors conclude that treatment with daridorexant for up to 12 months was well tolerated, and efficacy analyses suggest that the sustained improvements in sleep and daytime functioning support its use for long-term treatment of insomnia disorder.

The US Food and Drug Administration approved daridorexant (brand name QUVIVIQ) 25 mg and 50 mg for the treatment of adult patients with insomnia in 2022.