What is the mechanism of action of eszopiclone (Lunesta) and is it habit-forming?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: May 18, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Eszopiclone is a non-benzodiazepine sedative-hypnotic medication that works by enhancing the activity of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain, and it is habit-forming with potential for dependence and abuse. The mechanism of action of eszopiclone involves binding to GABA-A receptors, specifically at or near the benzodiazepine binding site, which increases chloride ion flow through the channel, resulting in neuronal hyperpolarization and central nervous system depression [ 1 ]. This action helps induce and maintain sleep. Some key points to consider when prescribing eszopiclone include:

  • It is classified as a Schedule IV controlled substance in the United States [ 1 ]
  • Physical and psychological dependence can develop, especially with prolonged use or higher doses [ 1 ]
  • Patients may experience withdrawal symptoms if the medication is stopped abruptly after regular use, including rebound insomnia, anxiety, irritability, and in severe cases, seizures [ 1 ]
  • It is typically recommended for short-term use (usually 7-10 days) and should be discontinued gradually under medical supervision [ 1 ]
  • The lowest effective dose should be used, and patients should be monitored for signs of dependence or misuse [ 1 ]

From the FDA Drug Label

The precise mechanism of action of eszopiclone as a hypnotic is unknown, but its effect is believed to result from its interaction with GABA-receptor complexes at binding domains located close to or allosterically coupled to benzodiazepine receptors

  • Mechanism of Action: The mechanism of action of eszopiclone is believed to result from its interaction with GABA-receptor complexes.
  • Habit Forming: The provided drug label does not directly address whether eszopiclone is habit forming 2.

From the Research

Mechanism of Action

  • Eszopiclone acts by binding to the GABA(A) receptor, with more selectivity for certain subunits of the GABA(A) receptor compared to benzodiazepine hypnotics 3.
  • This selective binding is thought to contribute to its sedative-hypnotic activity.

Habit Formation

  • Eszopiclone has a lower risk of dependence and abuse compared to benzodiazepines, although it is still a controlled substance 4, 5.
  • Studies have shown that eszopiclone does not produce significant tolerance or rebound insomnia, even with long-term use 3, 5, 6.
  • However, eszopiclone can produce euphoria effects similar to those of diazepam in benzodiazepine drug addicts, suggesting some potential for abuse 3.
  • The risk of dependence and abuse is generally considered to be lower with eszopiclone compared to benzodiazepines, but it is still important to use the medication as directed and under the guidance of a healthcare professional.

Efficacy and Safety

  • Eszopiclone has been shown to be effective in improving sleep onset and maintenance in adults with primary insomnia, with moderate effects on sleep efficacy outcomes 7.
  • The medication has also been shown to be safe and well-tolerated, with common adverse events including unpleasant taste, dry mouth, somnolence, and dizziness 7, 6.
  • Eszopiclone has been approved for use in the US as an oral, once-nightly therapy for insomnia in adults, and is also under review by the European Medicines Agency 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Eszopiclone: its use in the treatment of insomnia.

Neuropsychiatric disease and treatment, 2007

Research

Eszopiclone for the treatment of insomnia.

Expert opinion on pharmacotherapy, 2006

Research

Eszopiclone for insomnia.

The Cochrane database of systematic reviews, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.