Non-benzodiazepine hypnotic (“Z-drug”)
Selective GABA-A receptor agonist that binds to the benzodiazepine-1 (BZ1) receptor subtype, enhancing GABAergic inhibition to promote sleep initiation. Its rapid onset and ultrashort half-life make it effective for sleep-onset insomnia but not for sleep maintenance.
Short-term treatment of sleep-onset insomnia
Middle-of-the-night awakenings (if ≥4 hours of sleep remain), insomnia associated with anxiety or depression, circadian rhythm disturbances
Oral capsule (5 mg, 10 mg)
Start at 5–10 mg p.o. immediately before bedtime. May be increased to 20 mg as tolerated in adults without hepatic impairment.
5–20 mg p.o. nightly
Half-life is approximately 1 hour, with rapid onset. Metabolized primarily via aldehyde oxidase and CYP3A4, with minimal active metabolites.
Dizziness, headache, somnolence, impaired coordination, and abnormal dreams
Complex sleep behaviors (e.g., sleepwalking, sleep-driving), hallucinations, and rebound insomnia
Monitor for complex sleep-related behaviors, cognitive or motor impairment, and next-day functioning, especially in older adults.
Complex sleep behaviors, including sleepwalking, sleep-driving, and engaging in activities while not fully awake, which may result in serious injury or death.
Zaleplon may be especially useful for patients experiencing difficulty falling asleep who require a medication with minimal risk of next-day sedation. It may be suitable for occasional middle-of-the-night dosing if the patient has at least 4 hours of planned sleep remaining. Caution is warranted in elderly individuals, those with traumatic brain injury (TBI), or neurocognitive disorders due to increased susceptibility to falls, confusion, and disorientation. Avoid concurrent use with other sedative-hypnotics or alcohol.