Daridorexant (Quviviq) for Insomnia (Sleeping Pill)

Описание: Transcript:
Hello, I’m Dr. Diane MacIntosh, a psychiatrist and co-founder of SwitchRx.
This is a SwitchRx practical review of daridorexant.

Daridorexant is an insomnia treatment sold under the brand name Quviviq in Canada, the United States, and other international jurisdictions. It is indicated for adults with insomnia characterized by difficulty with sleep onset and/or sleep maintenance.

Daridorexant is a DORA—a dual orexin receptor antagonist. DORAs have been commercially available since 2014. They are not typical sedatives; their novel mechanism of action offers important advantages over older sedative–hypnotic treatments.

Orexin receptors are widely expressed in the brain, and orexin activity promotes wakefulness and arousal. At night, excessive orexin activity can contribute to insomnia. Inhibiting orexin receptors decreases the wake drive, facilitating both sleep onset and sleep maintenance, while preserving the ability to awaken to external stimuli.

We often think of insomnia treatment as increasing sedation. Instead, think of insomnia as the brain’s “wake switch” being left on at night. DORAs turn down that wake switch, reducing wakefulness or arousal.

Benzodiazepines and “Z-drugs” are broad CNS sedatives that can reduce orexin activity, but their effects may extend into daytime hours and cause impairment.

Before starting medication, ensure your patient understands and is doing their best with sleep hygiene. While sometimes challenging to access, CBT-I (cognitive behavioral therapy for insomnia) has demonstrated efficacy as a first-line treatment.

Set appropriate expectations when starting a DORA, especially for patients used to older insomnia medications. Because of the mechanism of action, patients should not expect an immediate sedative “knock-out” effect. Advise taking the dose 30 minutes before bedtime to allow sleep to occur naturally. Some aspects of sleep may improve right away, but full benefit builds over time; allow about four weeks before determining response.

Dosing (Canada): The daridorexant dose for adults is 50 mg taken 30 minutes before bedtime. Only the 50 mg tablet is available in Canada (the Health Canada–approved dose). It should be taken when at least seven hours remain before planned awakening. No dose adjustment is required for patients over 65 years, and it is not indicated for those under 18. It may be taken with or without food, though sleep onset may be delayed if taken with or soon after a large meal. Daridorexant is contraindicated in narcolepsy.

Switching and tapering: Cross-tapering from a benzodiazepine or a Z-drug—especially from higher doses—may take many months. SwitchRx guidance, based on evidence and clinical experience, suggests not initiating the taper of the older agent until two to three weeks after starting daridorexant (sometimes longer). If rebound insomnia emerges during taper, slow the taper and ensure comorbid conditions (e.g., anxiety or depression) are adequately treated.

Pharmacology: Daridorexant has a short Tmax for relatively rapid onset, an expected duration of about eight hours, and a rapid post-peak decline in plasma concentrations to minimize next-morning residual effects. It is a potent, selective DORA with equipotent binding at orexin-1 and orexin-2 receptors; major metabolites do not contribute to clinical effect.

Drug interactions: Daridorexant is extensively metabolized by CYP3A4. Avoid co-administration with strong CYP3A4 inhibitors. If used with a moderate CYP3A4 inhibitor, do not exceed 25 mg. Strong or moderate CYP3A4 inducers reduce daridorexant exposure and may necessitate a higher dose.

Benefits vs older hypnotics:
• Increases both REM and non-REM sleep without altering normal sleep stage proportions.
• No rebound insomnia reported after discontinuation.
• No evidence of abuse, addiction, or withdrawal upon discontinuation.
• Favorable safety in older adults, with no increased risk of adverse events or next-morning residual effects at 50 mg.
• Lower fall risk compared with Z-drugs, benzodiazepines, or trazodone.
• Preserves the ability to respond to external stimuli during the night.

Adverse effects: Generally mild and not dose-dependent. The most common are headache, somnolence, fatigue, and dizziness. At 200 mg (four times the recommended dose), daridorexant did not prolong the QTc interval.

Less common events: According to the product monograph, sleep paralysis occurred in 0.5% (25 mg) and 0.3% (50 mg) of patients versus none with placebo. Hypnagogic/hypnopompic hallucinations were reported in 0.6% at 25 mg, with no cases at 50 mg or placebo. Complex sleep behaviors (e.g., sleep driving, preparing/eating food, making phone calls, or sexual activity with amnesia) have been reported with other hypnotics; discontinue any hypnotic if complex sleep behaviors occur.

Special populations: Reduce the dose for moderate hepatic impairment. No renal dose adjustment is required, regardless of severity.