Can a patient with insomnia who took a single dose of eszopiclone 3 mg (Lunesta) and experienced hourly awakenings safely combine it with hydroxyzine or try another medication before discontinuing the hypnotic?

Yes, Continue Eszopiclone 3 mg for Several More Nights Before Discontinuing

Your instinct is correct—one night is insufficient to judge eszopiclone's efficacy, and the patient should continue the medication for at least 7–10 consecutive nights before considering it a failure. 1

Why One Night Is Not Enough

• The FDA label explicitly states that failure of insomnia to remit after 7–10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness, meaning the drug needs at least this duration to demonstrate efficacy before concluding it has failed. 1
• The American Academy of Sleep Medicine recommends reassessing patients after 1–2 weeks to evaluate changes in sleep-onset latency, total sleep time, nocturnal awakenings, and daytime functioning—not after a single dose. 2
• Eszopiclone's clinical trials demonstrated sustained improvements over weeks to months, not single nights; the drug requires consistent nightly dosing to achieve its full therapeutic effect. 3, 4, 5

Regarding Combination with Hydroxyzine

Do NOT add hydroxyzine or any other sedating agent to eszopiclone. 6, 1

• The FDA warns that combining eszopiclone with other CNS depressants (including antihistamines like hydroxyzine) significantly increases the risk of complex sleep behaviors (sleep-driving, sleep-walking), respiratory depression, cognitive impairment, falls, and next-day psychomotor impairment. 1
• The American Academy of Sleep Medicine explicitly recommends against using over-the-counter antihistamines for insomnia due to lack of efficacy data, strong anticholinergic effects (confusion, urinary retention, falls, daytime sedation, delirium), and tolerance development after only 3–4 days. 7
• Creating polypharmacy with multiple sedating agents markedly increases risks without improving outcomes; eszopiclone should be used as monotherapy. 6

Correct Management Strategy

Continue Eszopiclone Alone for 7–10 Nights

• Instruct the patient to take eszopiclone 3 mg nightly for at least 7–10 consecutive nights before judging efficacy, as this is the minimum duration required to assess response. 1
• Eszopiclone should be taken immediately before bedtime (within 30 minutes) with at least 7 hours remaining before planned awakening to minimize next-day impairment. 1
• The patient should avoid alcohol completely while taking eszopiclone, as alcohol markedly increases the risk of complex sleep behaviors and respiratory depression. 1

Simultaneously Initiate Cognitive Behavioral Therapy for Insomnia (CBT-I)

• The American Academy of Sleep Medicine issues a strong recommendation that all adults with chronic insomnia receive CBT-I as initial treatment before or alongside any pharmacotherapy, as it provides superior long-term outcomes with sustained benefits after medication discontinuation. 2, 7
• CBT-I includes stimulus control (use bed only for sleep, leave bed if unable to fall asleep within 20 minutes), sleep restriction (limit time in bed to approximate actual sleep time plus 30 minutes), relaxation techniques, and cognitive restructuring of negative sleep beliefs. 7
• Short-term hypnotic treatment should always be supplemented with behavioral interventions, not used in isolation. 2

Reassess After 1–2 Weeks

• After 7–14 nights of eszopiclone, evaluate:
  • Sleep-onset latency (time to fall asleep)
  • Total sleep time
  • Number and duration of nocturnal awakenings
  • Daytime functioning and alertness
  • Adverse effects (unpleasant/metallic taste, morning sedation, dizziness, headache) 2, 8
• If the patient reports complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating), discontinue eszopiclone immediately—this is an absolute contraindication to continued use. 1

If Eszopiclone Fails After 7–10 Nights

Switch to an Alternative First-Line Agent (Do Not Add)

• Low-dose doxepin 3–6 mg for sleep-maintenance insomnia—reduces wake after sleep onset by 22–23 minutes, has minimal anticholinergic effects at hypnotic doses, and carries no abuse potential. 2, 7
• Suvorexant 10 mg (orexin-receptor antagonist) for sleep-maintenance insomnia—reduces wake after sleep onset by 16–28 minutes through a different mechanism than benzodiazepine-type agents. 2, 7
• Zolpidem 10 mg (5 mg if elderly) for combined sleep-onset and maintenance—shortens sleep-onset latency by ~25 minutes and increases total sleep time by ~29 minutes. 2, 7

Evaluate for Underlying Sleep Disorders

• If insomnia persists beyond 7–10 days despite appropriate eszopiclone dosing, evaluate for comorbid sleep disorders such as sleep apnea, restless-legs syndrome, periodic limb movement disorder, or circadian-rhythm disorders. 1, 7
• The FDA label states that worsening of insomnia or emergence of new thinking or behavior abnormalities may indicate an unrecognized psychiatric or physical disorder that requires evaluation. 1

Common Pitfalls to Avoid

• Judging eszopiclone efficacy after a single night—the drug requires 7–10 consecutive nights to demonstrate full therapeutic effect. 1
• Adding hydroxyzine or other sedating agents to eszopiclone—this creates dangerous polypharmacy with markedly increased risks of respiratory depression, cognitive impairment, falls, and complex sleep behaviors. 6, 1
• Failing to initiate CBT-I alongside eszopiclone—behavioral therapy provides more durable benefits than medication alone and facilitates eventual medication tapering. 2, 7
• Using adult dosing in elderly patients—maximum dose is 2 mg in patients ≥65 years due to increased sensitivity and fall risk. 1
• Continuing eszopiclone long-term without periodic reassessment—FDA labeling indicates short-term use (≤4 weeks) for acute insomnia; evidence beyond 4 weeks is limited. 2, 7