What is more effective with fewer adverse effects for insomnia treatment: Zolpidem (nonbenzodiazepine hypnotic) or Eszopiclone (nonbenzodiazepine hypnotic)?

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Last updated: April 27, 2025 • View editorial policy

From the Guidelines

Eszopiclone is generally considered to have a slightly better side effect profile compared to zolpidem for treating insomnia, with fewer instances of complex sleep behaviors and a longer duration of action. Both zolpidem and eszopiclone are effective for treating insomnia, but the choice between them should be individualized based on a patient's specific sleep problems, medical history, and previous response to sleep medications 1.

Key Considerations

  • Eszopiclone typically causes fewer instances of complex sleep behaviors (like sleep-walking, sleep-eating, or sleep-driving) compared to zolpidem 1.
  • Eszopiclone has a longer duration of action, which may be beneficial for those who have trouble staying asleep throughout the night 1.
  • Both medications can cause morning grogginess, but this is often more pronounced with zolpidem, especially in older adults or women 1.
  • Both medications should be used for short periods (generally 7-10 days) as they can lead to dependence with prolonged use 2.
  • Neither medication should be combined with alcohol or other central nervous system depressants 2.

Dosage and Administration

  • Eszopiclone is usually started at 1-2 mg before bedtime 1.
  • Zolpidem is typically prescribed at 5-10 mg before bedtime 1.

Patient-Specific Factors

  • The choice between eszopiclone and zolpidem should be based on a patient's specific sleep problems, medical history, and previous response to sleep medications 1, 2.
  • Some patients may respond better to one medication than the other despite the general trends in side effect profiles 1.

From the Research

Comparison of Zolpidem and Eszopiclone for Insomnia

  • Both Zolpidem and Eszopiclone are nonbenzodiazepine hypnotic agents used for the treatment of insomnia.
  • Eszopiclone has been shown to significantly improve sleep onset and sleep maintenance compared to placebo in adult and elderly patients with primary insomnia 3, 4, 5.
  • Zolpidem has been associated with cognitive effects such as impaired verbal memory and attention, as well as slower speed of processing 6.
  • Eszopiclone has been found to have a more favorable adverse-effect profile, with common side effects including unpleasant taste, headache, and dry mouth 3, 4, 5.
  • A systematic review and meta-analysis found that eszopiclone had a moderate effect on sleep onset and maintenance, with no significant evidence of harm when taken as recommended 5.
  • Zolpidem has been associated with a higher risk of adverse events, including somnolence, dizziness, and rebound insomnia 6.
  • Eszopiclone has been shown to be effective for long-term treatment of insomnia, with sustained efficacy over 6 months of nightly treatment 7.

Side Effects and Safety

  • Eszopiclone has been found to have a lower risk of adverse events compared to zolpidem, including a lower risk of somnolence, dizziness, and rebound insomnia 5, 6.
  • Zolpidem has been associated with a higher risk of cognitive impairment, including impaired verbal memory and attention 6.
  • Eszopiclone has been found to have a more favorable pharmacokinetic profile, with rapid absorption and no evidence of tolerance or rebound insomnia 3, 4.

Efficacy and Effectiveness

  • Eszopiclone has been shown to be effective for the treatment of insomnia, with significant improvements in sleep onset and sleep maintenance compared to placebo 3, 4, 5.
  • Zolpidem has been associated with a higher risk of adverse events and cognitive impairment, which may impact its effectiveness for long-term treatment of insomnia 6.
  • Eszopiclone has been found to be effective for long-term treatment of insomnia, with sustained efficacy over 6 months of nightly treatment 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.