How does Spravata (eszopiclone) work to treat insomnia?

How Eszopiclone (Spravata) Works to Treat Insomnia

Eszopiclone works by selectively binding to GABA-A receptors in the brain, enhancing inhibitory neurotransmission to promote sleep onset and maintenance without significantly altering sleep architecture. 1

Mechanism of Action

Eszopiclone is a non-benzodiazepine hypnotic agent belonging to the cyclopyrrolone class. Its primary mechanism involves:

• Selective binding to specific subunits of the GABA-A receptor complex 1
• Enhancement of GABA-mediated inhibitory effects in the central nervous system
• Unlike benzodiazepines, eszopiclone demonstrates greater selectivity for certain GABA-A receptor subunits 1
• Rapid absorption with peak plasma concentrations reached within 1-1.6 hours after administration 1
• Mean elimination half-life of approximately 6 hours (9 hours in elderly patients) 1

Clinical Effects on Sleep Parameters

Eszopiclone produces several measurable improvements in sleep:

• Reduces sleep onset latency (SOL) by approximately 19 minutes 2
• Increases total sleep time (TST) by approximately 45 minutes 2
• Reduces wake time after sleep onset (WASO) by approximately 11 minutes 2
• Improves sleep efficiency and overall sleep quality 2
• Unlike benzodiazepines, eszopiclone does not significantly alter slow wave sleep (stages 3 and 4) or REM sleep 1

Dosing and Administration

The FDA-approved dosing for eszopiclone is:

• Adults: 2-3 mg taken immediately before bedtime 3
• Elderly patients: 1-2 mg taken immediately before bedtime 3
• Lower doses may be appropriate for patients with severe hepatic impairment 4
• Should be taken right before getting into bed, not sooner 3
• Should only be taken when able to get a full night's sleep (7-8 hours) 3

Efficacy in Different Populations

Eszopiclone has demonstrated efficacy in multiple populations:

• In adults with chronic insomnia, eszopiclone 3 mg improved global outcomes compared to placebo (50% vs 19% achieved remission) 2
• In elderly patients, eszopiclone 2 mg increased the percentage of patients having a minimum important difference in global outcomes versus placebo (37% vs 24%) 2
• Efficacy has been demonstrated in both short-term and long-term (up to 6 months) clinical trials 3

Safety Considerations and Side Effects

Common side effects include:

• Unpleasant or bitter taste (most common) 3, 1
• Headache 3, 1
• Somnolence 2
• Dry mouth 3, 1
• Dizziness 3

Important safety warnings:

• May cause complex sleep behaviors (sleep-walking, sleep-driving) 3
• Next-day impairment of driving and cognitive function may occur 3
• Should not be taken with alcohol or other CNS depressants 3
• Potential for dependence and withdrawal symptoms upon discontinuation 1
• Rebound insomnia may occur following withdrawal, particularly with the 2 mg dose 1

Long-Term Use

Unlike many other hypnotics:

• Eszopiclone has been studied for long-term use (up to 12 months) 1
• No evidence of tolerance development during 12 months of treatment 1, 5
• Sustained beneficial effects on sleep induction and maintenance with long-term use 1

Clinical Considerations

• The American College of Physicians recommends cognitive behavioral therapy for insomnia (CBT-I) as first-line treatment for chronic insomnia 2
• Pharmacological therapy, including eszopiclone, should be considered when CBT-I alone is unsuccessful 2
• The benefits of eszopiclone 2 mg and 3 mg are generally judged to be greater than potential harms 2
• The FDA has approved eszopiclone for short-term use (4-5 weeks), though clinical trials have demonstrated efficacy and safety for longer periods 2

Eszopiclone represents an effective option for treating insomnia with demonstrated benefits for both sleep onset and maintenance, with a relatively favorable side effect profile compared to some other hypnotic medications.