Drug Interaction Between Lunesta (Eszopiclone) and Buspirone
Eszopiclone and buspirone can be taken together safely, as there is no clinically significant pharmacokinetic or pharmacodynamic interaction between these two medications. 1
Evidence for Safety of Concurrent Use
Buspirone does not potentiate the sedative effects of hypnotic medications, including benzodiazepine-type hypnotics, when administered concomitantly on a short-term basis, and this lack of interaction extends to non-benzodiazepine hypnotics like eszopiclone. 1
Buspirone exhibits minimal drug-drug interactions due to its unique mechanism of action through 5-HT1A receptors rather than GABA receptors, making it pharmacologically distinct from eszopiclone's GABA(A) receptor binding mechanism. 2
Eszopiclone is primarily metabolized by CYP3A4, while buspirone undergoes extensive metabolism through hydroxylation and dealkylation pathways with minimal involvement of cytochrome P450-mediated interactions, reducing the likelihood of metabolic interference between the two drugs. 3, 4
Practical Clinical Guidance
Take eszopiclone 2–3 mg (1 mg if age ≥65 years) within 30 minutes of bedtime with at least 7 hours remaining before planned awakening, regardless of buspirone timing. 5
Continue buspirone on its usual dosing schedule (typically 15–30 mg daily in divided doses) without adjustment when adding eszopiclone, as the anxiolytic does not interfere with hypnotic efficacy. 1, 2
Monitor for additive CNS depression during the first 1–2 weeks of combined therapy, though this risk is substantially lower than with benzodiazepine combinations because buspirone causes only minimal sedation and does not potentiate alcohol or other CNS depressants. 1, 2
Safety Considerations Specific to Eszopiclone
Patients may experience next-day drowsiness and should avoid driving or operating machinery until fully awake, as eszopiclone remains at levels high enough to interfere with morning activities even without buspirone co-administration. 6
The most common side effect is unpleasant or bitter/metallic taste (7–26% of patients), which is dose-related and unrelated to buspirone use. 6
Older adults (≥65 years) require dose reduction to 1–2 mg due to increased elimination half-life (9 hours vs. 6 hours in younger adults) and heightened risk of falls, confusion, and morning sedation. 6, 4
Common Pitfalls to Avoid
Do not assume that buspirone's anxiolytic properties will worsen insomnia—buspirone lacks the activating effects of SSRIs and does not interfere with sleep architecture when combined with hypnotics. 1, 2
Avoid prescribing eszopiclone without first initiating Cognitive Behavioral Therapy for Insomnia (CBT-I), as behavioral therapy provides superior long-term outcomes and should be implemented alongside any pharmacotherapy. 5
Do not combine eszopiclone with benzodiazepines or other sedative-hypnotics, as this creates dangerous polypharmacy with markedly increased risks of respiratory depression, falls, and cognitive impairment—buspirone does not carry this risk. 5