What are the effects of long-term eszopiclone ( Lunesta ) use for insomnia lasting more than 5 years?

Long-Term Eszopiclone Use Beyond 5 Years: Evidence and Recommendations

There is insufficient evidence to support eszopiclone use beyond 6 months, and current guidelines explicitly state that evidence does not support long-term use exceeding this duration. 1

Critical Evidence Gap

The longest controlled trials of eszopiclone extend only to 6-12 months, creating a substantial evidence void for use beyond this timeframe. 1, 2, 3 The American College of Physicians explicitly states that "evidence is insufficient to evaluate the balance of the benefits and harms of long-term use of pharmacologic treatments in adults with chronic insomnia disorder." 1

FDA-Approved Duration vs. Clinical Reality

• The FDA has approved eszopiclone and other hypnotics for short-term use only (4-5 weeks), and explicitly recommends against extended use without reevaluation. 1
• The FDA further recommends that insomnia not remitting within 7-10 days of treatment warrants further evaluation for underlying causes. 1
• Despite this, the American Academy of Sleep Medicine acknowledges that chronic hypnotic medication "may be indicated for long-term use in those with severe or refractory insomnia or chronic comorbid illness." 1

Potential Harms of Prolonged Use (>5 Years)

Observational studies demonstrate serious adverse effects associated with chronic hypnotic use that were not captured in short-term RCTs:

• Dementia risk increases with prolonged hypnotic exposure. 1
• Serious injury and fractures occur more frequently, particularly concerning for older adults. 1
• Daytime impairment, "sleep driving," behavioral abnormalities, and worsening depression are FDA-labeled warnings. 1
• Dependence and abuse potential exists, with eszopiclone at doses of 6-12 mg producing euphoria effects similar to diazepam 20 mg in benzodiazepine-dependent individuals. 2

What the Evidence Actually Shows

The longest available data (6-12 months) demonstrates:

• No tolerance development during 12 months of treatment. 2, 3
• Sustained efficacy for sleep onset (12-minute reduction in latency) and maintenance (17-minute reduction in wake time, 28-minute increase in total sleep time). 4
• No rebound insomnia after 8 weeks of treatment upon discontinuation. 5
• However, one study showed rebound insomnia following 2 mg discontinuation in non-elderly subjects. 2

Clinical Algorithm for Patients on Long-Term Eszopiclone (>5 Years)

For patients already taking eszopiclone beyond evidence-supported durations:

1. Immediately initiate cognitive behavioral therapy for insomnia (CBT-I) as the evidence-based first-line treatment, which can facilitate medication tapering. 1

2. Assess for underlying or new comorbid conditions that may perpetuate insomnia (depression, anxiety, pain syndromes, sleep apnea, restless legs syndrome). 1

3. Implement structured tapering protocol:

   • Transition to intermittent dosing (3 nights per week) rather than nightly use. 1
   • Use "as needed" dosing based on actual sleep need. 1
   • Employ lowest effective maintenance dose. 1

4. Monitor closely for:

   • Cognitive decline or memory impairment (dementia risk). 1
   • Falls or balance problems (fracture risk, especially in elderly). 1
   • Behavioral changes or mood worsening. 1
   • Signs of tolerance (dose escalation requests). 1

5. Follow-up schedule: Every few weeks initially during taper, then regularly for ongoing assessment of effectiveness and adverse effects. 1

Common Pitfalls to Avoid

• Do not continue prescribing without attempting CBT-I, which has moderate-quality evidence for efficacy and facilitates medication discontinuation. 1
• Do not ignore the 4-5 week FDA approval window as a signal that longer use requires exceptional justification and heightened monitoring. 1
• Do not assume short-term safety data extrapolates to 5+ years, as observational studies reveal harms not apparent in controlled trials. 1
• Do not prescribe nightly dosing indefinitely when intermittent or as-needed strategies may reduce cumulative exposure and risk. 1

The Bottom Line

After 5+ years of eszopiclone use, the patient is in uncharted territory with no supporting evidence for continued safety or efficacy. The priority must shift to morbidity and mortality reduction by minimizing exposure to a medication with known serious adverse effects (dementia, falls, fractures) while transitioning to evidence-based non-pharmacological treatment (CBT-I). 1