Can an adult patient with a history of depression or anxiety, currently taking sertraline, be started on Lunesta (eszopiclone) for insomnia?

Can a Patient on Sertraline Be Started on Lunesta?

Yes, Lunesta (eszopiclone) can be safely started in a patient taking sertraline, but only after initiating Cognitive Behavioral Therapy for Insomnia (CBT-I) first, and the combination should be used to address both the underlying depression/anxiety and insomnia simultaneously. 1, 2

Treatment Algorithm for This Patient

Step 1: Initiate CBT-I Immediately

• CBT-I must be started before or alongside any sleep medication, as it provides superior long-term outcomes with sustained benefits after medication discontinuation 2
• CBT-I includes stimulus control therapy, sleep restriction therapy, relaxation techniques, and cognitive restructuring, deliverable through individual therapy, group sessions, telephone-based programs, or web-based modules 2
• This is non-negotiable—pharmacotherapy should supplement, not replace, behavioral interventions 2

Step 2: Add Eszopiclone if CBT-I Alone is Insufficient

• Start eszopiclone 2-3 mg at bedtime for both sleep onset and maintenance insomnia 2
• Eszopiclone demonstrates moderate-to-large improvement in sleep quality with 28-57 minute increase in total sleep time 2
• The combination of eszopiclone with an SSRI (specifically studied with escitalopram, a close relative of sertraline) showed significantly improved sleep, daytime functioning, and anxiety measures with good tolerability 3

Step 3: Monitor Specific Parameters

• Assess sleep latency, wake after sleep onset, total sleep time, and daytime functioning after 1-2 weeks 2
• Watch for adverse effects including unpleasant taste (most common), headache, dry mouth, and somnolence 3
• Monitor for complex sleep behaviors (sleep-driving, sleep-walking) and discontinue immediately if they occur 2

Why This Combination is Appropriate

Sertraline is the preferred SSRI in this context because it has been extensively studied and appears to have a lower risk of QTc prolongation than citalopram or escitalopram 1. The combination addresses both conditions:

• For depression/anxiety: Sertraline continues as the primary treatment 1
• For insomnia: Eszopiclone provides effective sleep improvement without significant drug interactions with sertraline 3, 4

Research specifically demonstrates that eszopiclone combined with an SSRI (escitalopram) resulted in 63% anxiety response rate versus 49% with SSRI alone, with improved sleep maintained throughout the 8-week treatment period 3.

Critical Safety Considerations

Drug Interaction Profile

• Sertraline has a low potential for cytochrome P450 interactions, making it safer for combination therapy than other SSRIs 4
• No dosage adjustments are needed for either medication when used together 4
• The overall adverse event rate with eszopiclone plus SSRI therapy was 77.6%, with most events being mild to moderate 3

Avoid These Common Pitfalls

• Do not use over-the-counter antihistamines (diphenhydramine/Benadryl) instead—they are explicitly not recommended due to anticholinergic effects and lack of efficacy 2
• Do not use trazodone—it is explicitly not recommended for insomnia treatment despite common off-label use 2
• Do not skip CBT-I—medication alone provides inferior long-term outcomes 2
• Do not use long-term without reassessment—FDA labeling indicates hypnotics are intended for short-term use, though eszopiclone is approved for longer duration 2

Alternative First-Line Options if Eszopiclone is Contraindicated

If eszopiclone cannot be used, consider these alternatives in order:

1. Low-dose doxepin 3-6 mg for sleep maintenance—reduces wake after sleep onset by 22-23 minutes with minimal side effects 2
2. Zolpidem 10 mg (5 mg if elderly) for sleep onset and maintenance—reduces sleep latency by 25 minutes 2
3. Ramelteon 8 mg for sleep onset—melatonin receptor agonist with no dependence risk 2

Duration and Discontinuation Strategy

• After 8 weeks of combined therapy, reassess the need for continued eszopiclone 3
• When discontinuing eszopiclone, there is no evidence of rebound insomnia if tapered appropriately 3
• Continue CBT-I techniques indefinitely to maintain sleep improvements after medication discontinuation 2
• Anxiety and mood improvements from sertraline should be maintained even after eszopiclone discontinuation 3