What is the recommended dosing when prescribing escitalopram (Lexapro) and eszopiclone (Lunesta) together?

Dosing Lexapro and Lunesta Together

When prescribing escitalopram (Lexapro) and eszopiclone (Lunesta) together, use escitalopram 10-20 mg once daily (morning or evening) and eszopiclone 2-3 mg immediately before bedtime for adults aged 18-64 years, with dose reductions to escitalopram 10 mg and eszopiclone 2 mg for elderly patients (≥65 years). 1, 2

Standard Adult Dosing (Ages 18-64)

Escitalopram Dosing

• Start at 10 mg once daily, taken in the morning or evening with or without food 1
• May increase to 20 mg after minimum of 1 week if clinically indicated for depression or generalized anxiety disorder 1
• The 10 mg and 20 mg doses are both effective, though 20 mg did not demonstrate greater benefit than 10 mg in fixed-dose trials 1

Eszopiclone Dosing

• Start at 1 mg immediately before bedtime as the lowest effective dose 2
• May increase to 2 mg or 3 mg if clinically indicated, but be aware that higher doses (2-3 mg) increase risk of next-day impairment of driving and activities requiring full alertness 2
• Maximum dose is 3 mg once daily 2
• Do not take with or immediately after a heavy, high-fat meal as this slows absorption and reduces effectiveness on sleep latency 2

Elderly or Debilitated Patients (≥65 Years)

• Escitalopram: 10 mg/day is recommended for most elderly patients 1
• Eszopiclone: Maximum 2 mg in elderly or debilitated patients 2

Special Populations Requiring Dose Adjustments

Hepatic Impairment

• Escitalopram: 10 mg/day for patients with hepatic impairment 1
• Eszopiclone: Maximum 2 mg in patients with severe hepatic impairment 2

Renal Impairment

• Escitalopram: No adjustment needed for mild-to-moderate renal impairment; use with caution in severe renal impairment 1
• Eszopiclone: No dosage adjustment required for renal dysfunction 3

Evidence for Combination Therapy

The combination of eszopiclone and escitalopram is well-studied and safe. A large randomized, double-blind, placebo-controlled trial demonstrated that coadministration of eszopiclone 3 mg with escitalopram 10 mg for 8 weeks in patients with insomnia and comorbid generalized anxiety disorder resulted in significantly improved sleep, daytime functioning, anxiety, and mood compared to escitalopram alone 4. The combination was well tolerated with overall adverse event rates of 77.6% versus 67.9% with monotherapy, with the most common adverse events being unpleasant taste, headache, dry mouth, and somnolence 4.

Clinical Considerations

Timing of Administration

• Escitalopram can be taken morning or evening based on patient preference and tolerability 1
• Eszopiclone must be taken immediately before bedtime 2
• If escitalopram causes activation or worsens insomnia, consider morning dosing 5

Duration of Treatment

• Eszopiclone has no short-term usage restriction and is approved for long-term treatment of insomnia 6, 7, 8
• Escitalopram requires several months or longer of sustained therapy for acute episodes of major depressive disorder 1
• Periodically reassess the need for continued treatment with both medications 1

Drug Interactions

• No significant pharmacokinetic interaction exists between eszopiclone and escitalopram 4
• If patient is taking potent CYP3A4 inhibitors, limit eszopiclone to maximum 2 mg 2
• If combining with other CNS depressants, dosage adjustments of eszopiclone may be necessary due to potentially additive effects 2

Discontinuation Strategy

Escitalopram Discontinuation

• Gradual dose reduction is recommended rather than abrupt cessation to minimize discontinuation symptoms 1
• Monitor for withdrawal symptoms including irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania 1
• If intolerable symptoms occur, resume previous dose and taper more gradually 1

Eszopiclone Discontinuation

• After 8 weeks of eszopiclone treatment, no evidence of rebound insomnia was observed upon discontinuation in clinical trials 4
• However, clinical judgment should guide tapering strategy based on individual patient factors

Common Pitfalls to Avoid

• Do not exceed eszopiclone 3 mg in adults or 2 mg in elderly patients to minimize next-day impairment risk 2
• Screen for bipolar disorder before initiating escitalopram, as antidepressants can precipitate manic episodes 1
• Allow at least 14 days between discontinuing an MAOI and starting escitalopram, or vice versa 1
• Warn patients about next-day driving impairment with eszopiclone, particularly at 2-3 mg doses 2
• Do not assume insomnia will resolve with antidepressant alone—the combination approach provides superior outcomes for both sleep and psychiatric symptoms 4