Eszopiclone (Lunesta)

Class

Non-benzodiazepine hypnotic (“Z-drug”)

Mechanism

GABA-A receptor agonist that selectively binds to the benzodiazepine-1 (BZ1) receptor subtype, enhancing inhibitory GABAergic activity and promoting sleep onset and maintenance. Compared to other Z-drugs, it has a longer half-life, contributing to its utility in sleep-maintenance insomnia. 

FDA-Approved Use

Insomnia, particularly when characterized by difficulty falling asleep or staying asleep

Off-Label Use

Sleep disruption in posttraumatic stress disorder (PTSD) and circadian rhythm disturbances

Formulation

Oral tablet (1 mg, 2 mg, 3 mg)

Titration

Start at 1 mg p.o. nightly, taken immediately before bedtime. May be titrated to 2–3 mg as clinically indicated, using the lowest effective dose to minimize next-day impairment. 

Dose Range

1–3 mg p.o. nightly

Kinetics

Half-life of approximately 6 hours, with hepatic metabolism primarily via CYP3A4. Its longer duration of action may benefit sleep maintenance but increases risk of next-day sedation, particularly in older adults. 

Common AEs

Dysgeusia (metallic or bitter taste), sedation, dizziness, dry mouth, and next-day drowsiness 

Serious/Rare AEs

Complex sleep behaviors (e.g., sleepwalking, sleep-driving), anterograde amnesia, hallucinations, and rebound insomnia

Monitoring

Monitor for next-day sedation, cognitive or motor impairment, complex sleep behaviors, and mood or behavioral changes

Black Box Warning

Complex sleep behaviors, including sleepwalking, sleep-driving, and engaging in activities while not fully awake, which may result in serious injury or death.

Considerations

Use caution in patients with traumatic brain injury (TBI), dementia, or other cognitive disorders due to increased risk of confusion, sedation, and impaired coordination. In older adults, eszopiclone is generally not recommended for long-term use due to risk of cognitive and motor side effects. However, it may be considered in younger patients with sleep-maintenance insomnia who have not responded to non-pharmacologic treatments, with regular reassessment for efficacy and adverse effects.