eszopiclone

General Information

Eszopiclone is a non-benzodiazepine hypnotic (“Z-drug”) approved for insomnia, often used for sleep onset and sleep maintenance symptoms.

Key safety issues are complex sleep behaviors (boxed warning), next-day impairment, and additive sedation with alcohol or other CNS depressants—risks that are amplified in older adults and in serious mental illness with polypharmacy.

Eszopiclone is often used as a time-limited adjunct to CBT-I and sleep hygiene; persistent insomnia commonly prompts reassessment for untreated sleep apnea, circadian disorders, substance use, pain, and mood episodes before adding additional sedatives.

The eszopiclone compare view, eszopiclone evidence feed, and eszopiclone print page can support shared decision-making when aligning sleep goals with safety planning.

Dysgeusia (metallic/bitter taste) is common, and the lowest effective dose is typically used. Eszopiclone is often positioned as a time-limited adjunct to CBT-I and sleep hygiene. Short prescriptions with planned follow-up are common; complex sleep behaviors, next-day impairment, or unsafe nighttime behaviors generally prompt discontinuation.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Positive allosteric modulator of GABA-A receptors producing hypnotic effects.

Classified as a “Z-drug”; effects are dose dependent and interact strongly with other CNS depressants.

Like other hypnotics, eszopiclone can reduce symptoms but does not treat the underlying cause of insomnia; medication use is often paired with behavioral sleep strategies and treatment of comorbid psychiatric conditions.

• GABA-A receptor facilitation (non-benzodiazepine hypnotic class).

Metabolism and Pharmacokinetics

• Rapid absorption with Tmax ~1 hour and terminal half-life ~6 hours (label).
• Extensively metabolized; CYP3A4 and CYP2E1 are involved (label).
• <10% of drug is excreted unchanged in urine (label).
• Next-day impairment risk increases in older adults and severe hepatic impairment; dosing is often conservative and safety is reassessed after initiation or dose changes.

Dosing and Administration

• Typically taken immediately before bedtime, when able to remain in bed for a full night.
• Food can delay onset; when delayed onset is a concern, bedtime dosing is often separated from heavy meals. “Middle of the night” redosing is generally avoided.
• The lowest effective dose is typically used; maximum dosing is lower in severe hepatic impairment or with potent CYP3A4 inhibitors.
• Alcohol and other sedatives increase risk and are generally avoided; use is reassessed frequently, and open-ended refills are typically avoided.

Monitoring & Labs

• Next-day impairment (driving, work, falls) after initiation and dose changes; dosing is adjusted or discontinued if safety is compromised.
• Complex sleep behaviors; when they occur, discontinuation is typical.
• Mood and suicidality in patients with depression or serious mental illness.
• If continued beyond a brief course, taper attempts and CBT-I reinforcement to reduce rebound insomnia.

Sources: FDA/DailyMed label; AASM insomnia guideline; evidence reviews.

Adverse Effects

Interactions

• Alcohol and other CNS depressants (opioids, benzodiazepines, sedating antipsychotics) increase risk and are generally avoided.
• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir) increase exposure—lower doses and oversedation monitoring are common; inducers (e.g., rifampin, carbamazepine, St. John’s wort) may reduce efficacy.
• Combining with other sedative-hypnotics increases risk and is generally avoided when possible; if combinations are unavoidable, lower starting doses and closer follow-up are commonly used to reduce falls and driving risk.

Other Useful Information

• CBT-I and sleep hygiene are first-line; eszopiclone is often used for short, clearly bounded courses with stop plans.
• Generally avoided in untreated sleep apnea or when nighttime wandering is a safety concern.
• In chronic insomnia, underlying drivers are often addressed rather than escalating hypnotic doses.
• Short prescriptions with planned follow-up are common; complex sleep behaviors, next-day impairment, or unsafe nighttime behaviors generally prompt discontinuation.

References

1. Lunesta (eszopiclone) prescribing information — DailyMed (2025)
2. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline — Journal of Clinical Sleep Medicine (2017)
3. Efficacy and Acceptability of Pharmacological Interventions for Insomnia in Patients With Severe Mental Illness — Acta Psychiatrica Scandinavica (2025)
4. Residual effects of medications for sleep disorders on driving performance — European Neuropsychopharmacology (2024)