What is the recommended dosing of eszopiclone for insomnia in adults (including those ≥65 years), and what are its contraindications, precautions, and common adverse effects?

Eszopiclone Dosing and Clinical Guidance for Insomnia

Recommended Dosing

Eszopiclone 2 mg at bedtime is the recommended starting dose for adults aged 18–64 years, with titration to 3 mg if sleep maintenance remains inadequate after 1–2 weeks. 1, 2

Age-Specific Dosing

• Adults 18–64 years: Start 2 mg at bedtime; increase to 3 mg if clinically indicated for sleep maintenance 1, 2
• Adults ≥65 years: Start 1 mg at bedtime for sleep-onset difficulty; maximum 2 mg for sleep maintenance 1, 2
• Hepatic impairment (severe): Maximum 2 mg; start at 1 mg 1, 2
• Renal impairment: No dose adjustment required 3

Administration Instructions

• Take within 30 minutes of bedtime with at least 7 hours remaining before planned awakening 2
• Rapidly absorbed with peak concentrations at 1.0–1.6 hours 4, 3
• Mean elimination half-life is 6 hours in younger adults, increasing to approximately 9 hours in patients ≥65 years 4

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Clinical Efficacy

Eszopiclone demonstrates moderate-strength evidence for both sleep-onset and sleep-maintenance insomnia, with clinically significant improvements in objective sleep latency (≈19 minutes reduction) and total sleep time (28–57 minutes increase). 1, 5

Sleep Parameters Improved

• Sleep-onset latency: Reduced by ≈19 minutes versus placebo 1
• Total sleep time: Increased by 28–57 minutes 1, 2
• Wake after sleep onset: Reduced by ≈11 minutes 1
• Sleep efficiency: Clinically significant improvement demonstrated 1
• Sleep quality: Moderate-to-large subjective improvement 1

Remission Rates

• At 12 weeks, 50% of patients achieve remission (Insomnia Severity Index <7) compared with 19% on placebo 2

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Duration of Therapy

Unlike zolpidem and zaleplon, eszopiclone is not restricted to short-term use in its FDA labeling, though the American College of Physicians states evidence beyond 4 weeks is insufficient. 1, 2, 6

• Studies demonstrate sustained efficacy for up to 6–12 months without tolerance 1, 7, 4
• FDA labeling recommends short-term use for acute insomnia (≤4 weeks), though longer trials exist 1, 2
• Reassess efficacy and adverse effects after 1–2 weeks, then every 4–6 weeks 2
• Use the lowest effective dose for the shortest necessary duration 1, 2

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Contraindications and Precautions

Absolute Contraindications

• History of complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating) on any hypnotic 1, 2
• Known hypersensitivity to eszopiclone or zopiclone 8

Relative Contraindications and High-Risk Populations

• Severe hepatic impairment: Reduce maximum dose to 2 mg 1, 2
• Elderly patients (≥65 years): Maximum 2 mg due to increased sensitivity, fall risk, and prolonged half-life 1, 2
• Cognitive impairment or dementia risk: Observational data link hypnotics to increased dementia risk (hazard ratio 2.34) 1, 2
• High fall risk or osteoporosis: All hypnotics increase fracture risk 1, 2
• Concurrent CNS depressants: Combining multiple sedatives markedly increases respiratory depression, cognitive impairment, and fall risk 2

Drug Interactions

• Potent CYP3A4 inhibitors: Dose adjustment necessary; eszopiclone is metabolized via CYP3A4 3
• Alcohol: Must be avoided—markedly increases risk of complex sleep behaviors and respiratory depression 2

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Common Adverse Effects

The most common treatment-emergent adverse effects are unpleasant/bitter taste (most distinctive), headache, and somnolence. 1, 6, 7, 4, 3

Frequency of Adverse Effects

• Unpleasant/bitter taste: Most common and distinctive side effect 1, 6, 7, 4, 3
• Headache: Approximately 15–30% of patients 1, 4, 3
• Somnolence: Approximately 23% 1, 4
• Dry mouth: Common 7, 3
• Dizziness: Common 1, 6, 3
• Dyspepsia, diarrhea, nausea: Reported 7, 4
• Upper respiratory infection, urinary tract infection: Reported in trials 7, 4

Serious Adverse Effects

• Complex sleep behaviors: Sleep-driving, sleep-walking, sleep-eating—discontinue immediately if these occur 1, 2
• Next-day impairment: Eszopiclone 3 mg produces measurable psychomotor and memory deficits up to 11.5 hours after dosing; patients often do not perceive impairment 2
• Memory impairment: Higher incidence versus placebo per FDA medical reviews 1
• Psychiatric adverse effects: Depression, anxiety, abnormal thinking, behavioral changes 1
• Serious adverse events: 3% versus 1% placebo in one trial 1
• Falls and fractures: Increased risk, especially in elderly 1, 2

Withdrawal and Discontinuation

• Rebound insomnia: Reported following discontinuation of 2 mg dose in non-elderly subjects 4
• Withdrawal symptoms: Anxiety, abnormal dreams, hyperesthesia, nausea, upset stomach reported after discontinuation 4
• Taper gradually when discontinuing to avoid rebound insomnia, using CBT-I to support cessation 2
• No serious withdrawal effects or tolerance during 12 months of treatment 7, 4

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Abuse and Dependence Potential

• Unpublished data show eszopiclone 6–12 mg produces euphoria similar to diazepam 20 mg in benzodiazepine drug addicts 4
• For patients with substance-use history, consider ramelteon 8 mg (no abuse potential, no DEA scheduling) instead 2

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Essential Treatment Framework

All pharmacotherapy must be combined with Cognitive Behavioral Therapy for Insomnia (CBT-I), which provides superior long-term outcomes and sustained benefits after medication discontinuation. 1, 2

CBT-I Components

• Stimulus control: Use bed only for sleep; leave bed if unable to sleep within ≈20 minutes 2
• Sleep restriction: Limit time in bed to approximate total sleep time plus 30 minutes 2
• Relaxation techniques: Progressive muscle relaxation, guided imagery, breathing exercises 2
• Cognitive restructuring: Modify negative beliefs about sleep 2
• Sleep hygiene: Consistent bedtime/wake time, avoid caffeine ≥6 hours before bed, limit screen time 2

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Monitoring and Reassessment

• After 1–2 weeks: Assess sleep-onset latency, total sleep time, nocturnal awakenings, daytime functioning, and adverse effects (somnolence, bitter taste, headache, memory impairment) 1, 2
• Every 4–6 weeks: Determine whether hypnotic can be tapered as CBT-I effects consolidate 2
• If insomnia persists beyond 7–10 days: Evaluate for underlying sleep disorders (sleep apnea, restless-legs syndrome, circadian-rhythm disorders) 2

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Common Clinical Pitfalls

• Starting eszopiclone without implementing CBT-I: Leads to less durable benefit and higher relapse rates 2
• Using adult dosing in elderly patients: Age-adjusted dosing (maximum 2 mg for ≥65 years) is essential to reduce fall risk 1, 2
• Combining multiple sedative agents: Markedly increases respiratory depression, cognitive impairment, falls, and complex sleep behaviors 2
• Failing to reassess regularly: Efficacy, side effects, and continued need should be evaluated every 2–4 weeks 2
• Continuing long-term without periodic reassessment: FDA labeling indicates short-term use; routine use beyond 4 weeks requires justification 1, 2
• Allowing alcohol use: Alcohol must be avoided while on eszopiclone due to additive CNS depression 2