Orexin-Blocking Sleep Pills Compared: Suvorexant, Lemborexant and Daridorexant

If you’ve tried better sleep habits and still lie awake, your clinician may mention a newer type of sleep medicine. Instead of sedating the whole brain, orexin receptor antagonists block orexin, a chemical that helps keep you awake. Three are approved in the U.S. for trouble falling asleep, staying asleep or both.¹²³

Side by side

	Suvorexant	Lemborexant	Daridorexant
Usual dose	10 mg, up to 20 mg1	5 mg, up to 10 mg2	25 to 50 mg3
When	Within 30 minutes of bed1	Right before bed2	Within 30 minutes of bed3
Time needed in bed	At least 7 hours1	At least 7 hours2	At least 7 hours3

All three may work more slowly if taken with or soon after a meal.¹²³

What all three labels warn about

• Next-day drowsiness. They can impair alertness and coordination the next morning, and the effect can last several days after stopping in some people.² Taking one with less than a full night left raises the risk.²
• Other sedatives add up, including alcohol, opioids, benzodiazepines and some antidepressants.²
• Falls. Drowsiness raises fall risk, especially in older adults.²³
• Sleep paralysis, dream-like hallucinations at sleep onset or waking, and complex sleep behaviors such as sleep-walking or sleep-driving.²
• Worsening depression or suicidal thoughts.²
• Narcolepsy: none should be used.¹²³
• Controlled substances (Schedule IV).²³
• If insomnia continues after 7 to 10 days, the label advises checking for another cause.²³

Details that matter after 50

• Suvorexant levels run higher in women and in people with obesity, so the label urges care before raising the dose, especially for women with obesity.¹
• Lemborexant trials included 491 people 65 and older. Drowsiness was more common in that group at the 10 mg dose.²
• Daridorexant trials included about 39% people 65 or older. Drowsiness and fatigue became more likely with age, though no dose change is required.³ Rare throat swelling has been reported.³
• Interactions. Some common medicines that affect liver enzymes change the dose or rule these out.²³ Bring your full medicine list.

How the guideline fits in

The 2017 American Academy of Sleep Medicine guideline, written before the two newer pills were approved, gave a weak suggestion for suvorexant for trouble staying asleep.⁴ Behavioral treatment remains the recommended first step. Our guides to CBT for insomnia, suvorexant and next-day driving, trazodone and Z-drugs compare other options.

Questions to ask

1. Have we ruled out sleep apnea, restless legs, hot flashes or depression?
2. Which of these fits my other medicines and my liver health?
3. What if I wake at 4 a.m.? Can I still take it?
4. How will we decide whether it’s working?

Try: “I wake at 3 a.m. most nights and CBT-I has helped only a little. Would an orexin blocker suit me, given my blood pressure pills and the fact that I get up at night to use the bathroom?”

Did I Do That in My Sleep? includes a 14-Night Lights-Out Record and a Visit Brief. Use them to track bedtime, wake-ups and any morning grogginess. See the book.