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PubMed Clinical Q&A [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2008-2013.

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

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PubMed Clinical Q&A [Internet].

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Comparing Newer Drugs for Insomnia

, MD.

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Created: .

The treatment of insomnia involves behavioral changes, such as avoiding stressful activities prior to sleeping, and medications. Newer medications for insomnia include zolpidem, zaleplon, zopiclone, and eszopiclone, which work via GABA receptors, and ramelteon, which works via melatonin receptors.

These medications may have a different effect on treating sleep problems. For example, a drug with a shorter half-life might help to reduce the time it takes a person to fall asleep (reduce sleep latency), but be less effective in ensuring the person remains asleep throughout the night (sleep duration). To measure the degree and nature of sleep problems, patients may keep sleep diaries, or polysomnography may be used to record patterns of brain waves during sleeping.

The "Drug Class Review on Newer Drugs for Insomnia" compares the safety and effectiveness of six drugs. A summary of the findings is below.

How do newer drugs compare in the treatment of insomnia?

Zolpidem and zaleplon are similarly effective in helping patients fall asleep, including patients over the age of 65. In patients under the age of 65, zolpidem is more likely than zaleplon to cause rebound insomnia, which is the worsening of insomnia after treatment has finished.

Zolpidem (10 mg) and eszopiclone (2 mg or 3 mg) are similarly effective in reducing the number of times a person wakes up in the night, and also reducing the time it takes a person to fall asleep, as measured by polysomnography. [full review]

Zolpidem and zopiclone are similarly effective in improving insomnia, both when compared against each other, and when compared indirectly against placebo. Comparing all the newer insomnia drugs against placebo, a few differences were found. For example, sleep latency was shorter and sleep duration was longer with eszopiclone compared to ramelteon. But overall, there were no major differences between the drugs on any sleep outcome. [full review]

How do newer drugs for insomnia compare in safety?

When zolpidem is compared to:

  • Eszopiclone – there is no difference in next-day effects, such as morning sleepiness, daytime alertness, and daytime ability to function
  • Zaleplon – the rates of withdrawals from trials are similar
  • Zopiclone – the rates of adverse effects are similar [full review]

Compared to placebo, there is no increased risk of adverse events leading to withdrawal from trials for eszopiclone, ramelteon, zaleplon, zolpidem, or zopiclone. The risk of withdrawal due to adverse events was higher with zolpidem extended release than placebo.

There is no evidence comparing the long-term safety of the drugs. [full review]

Does age, gender, or race influence the safety or effectiveness of newer insomnia drugs?

In adults aged over 65, treatment with zolpidem and zaleplon gives similar results to those in younger adults. There is no difference in overall adverse effects, although daytime drowsiness is more common with zolpidem. Indirect evidence from placebo-controlled trials suggests that eszopiclone increases sleep duration more than zolpidem in elderly patients.

There is no evidence that one of the newer insomnia drugs is safer or more effective than another based on gender or race. [full review]

Drugs included in this review

Generic NameTrade Names
ZaleplonSonata, generic
ZolpidemAmbien, generic
Zolpidem extended-releaseAmbien-CR

Further information

Image th-hypnotics08.jpgThis PubMed Clinical Q&A was reviewed by Susan Carson, MPH.

For the full report and evidence tables, please see:
Carson S, McDonagh MS, Thakurta S, et al. Drug Class Review: Newer Drugs for Insomnia: Final Report Update 2 [Internet]. Portland (OR): Oregon Health & Science University; 2008 Oct. Available at:


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