Translation of a-t 2025; 56: 87

NO REBOUND IN PATIENTS TREATED WITH THE SLEEPING PILL DARIDOREXANT (QUVIVIQ)?

Daridorexant (QUVIVIQ) is currently being aggressively marketed, among other things with the statement that no signs of rebound insomnia occur after discontinuation. You pointed out significant rebound phenomena in 2023 (a-t 2023; 54: 1-3). Is there any new information available that supports the manufacturer's statement or changes your fundamental assessment?

N.N. (name etc. stated in a-t 11/2025)
Conflict of interest: none

The provider Idorsia advertises daridorexant (QUVIVIQ) as having "no signs of rebound insomnia".^e.g.1 In a phase III study relevant to the authorisation, patients receiving 50 mg (recommended dose) fell asleep an average of 10 minutes faster and lay awake at night for around 20 minutes less than those receiving a placebo (see a-t 2023; 54: 1-3).²

In response to the request for proof of the advertising statement, Idorsia³ referenced the assessment by the European Medicines Agency (EMA) according to which no rebound was observed in the pivotal studies.⁴ In fact, following a blinded change from 50 mg daridorexant to the placebo in the whole group, both time to fall asleep and time spent awake at night were numerically (slightly) shorter than at the start of the study (average of -15 minutes and -3 minutes).^2,5* However, this did not apply for people over the age of 65: based on the stratified subgroup analyses performed by the US drug authority FDA, they lay awake at night for approximately 20 minutes longer than before they started taking the medicine (95% confidence interval [CI] 11-28). According to the FDA's assessment, this indicates a risk of dependency and also a "robust risk of rebound for elderly patients".⁶

According to the FDA, the direct, considerable worsening in sleep following discontinuation is also clinically relevant – not a classic rebound but significant for patients (6). In the whole study population, the time to fall asleep after switching from 50 mg daridorexant to a placebo increased by an average of 16 minutes (95% CI 11-21) and the time spent awake at night increased by 25 minutes (95% CI 20-31). The FDA also estimates that the percentage of people whose waking phases increased by at least an hour after discontinuing the orexin inhibitor was more than 10% higher in absolute figures compared to those who had taken the placebo throughout.⁶

Since our last assessment, the price of the orexin inhibitor has fallen considerably to around € 2.90 per night (30 tablets of 50 mg: € 87.89), but it remains around three to four times as high as for generic drugs of the benzodiazepine temazepam (e.g. TEMAZEP-CT: 20 capsules of 10 mg € 17.64; € 0.88 per night) and the Z-drug zopiclone (e.g. ZOPICLODURA: 20 tablets of 7.5 mg € 15.24; € 0.76 per night), –Ed.

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