Can zopiclone (nonbenzodiazepine hypnotic agent) cause rebound insomnia?

Zopiclone and Rebound Insomnia

Yes, zopiclone can cause rebound insomnia, particularly following abrupt discontinuation after regular use. This effect is typically characterized by a temporary worsening of sleep parameters compared to baseline after stopping the medication.

Evidence for Rebound Insomnia with Zopiclone

• Rebound insomnia is defined as a dose-dependent temporary worsening in sleep parameters (latency, sleep efficiency, and number of awakenings) compared with baseline following discontinuation of treatment 1
• The FDA label for zopiclone (marketed as Lunesta in the US) specifically mentions that rebound insomnia can occur following discontinuation, characterized by the return of symptoms of chronic insomnia 1
• Clinical trials have shown that discontinuation-emergent effects with zopiclone are generally mild and appear to resolve by the second night after discontinuation 1
• Some studies have found evidence of rebound insomnia after withdrawal of zopiclone, limited primarily to the first night following discontinuation 2

Comparison with Other Hypnotics

• Zopiclone appears to have a lower propensity for causing rebound insomnia compared to traditional benzodiazepines, particularly those with short half-lives 3, 4
• In a comparative study, triazolam showed more significant rebound effects on total sleep time and sleep efficiency in the first night after discontinuation compared to zopiclone 5
• After withdrawal from zopiclone, only slight but not statistically significant rebound effects concerning sleep continuity were observed 5

Risk Factors and Management

• The risk of rebound insomnia appears to be related to:
  • Duration of treatment (longer treatment periods may increase risk) 2
  • Dosage (higher doses increase risk) 1
  • Abrupt versus gradual discontinuation 2
• To minimize rebound insomnia:
  • Use the lowest effective dose for the shortest duration possible 2
  • Consider gradual tapering rather than abrupt discontinuation 2
  • Be aware that symptoms typically peak on the first night after discontinuation 1, 5

Clinical Implications

• Patients should be informed about the possibility of rebound insomnia when starting zopiclone treatment 2
• Zopiclone is indicated for short-term use and should not be prescribed for more than 4 weeks to minimize the risk of dependence and rebound phenomena 3
• Rapid dose decrease or abrupt discontinuation can produce withdrawal symptoms, including rebound insomnia, similar to that seen with benzodiazepines 2
• The American Academy of Sleep Medicine notes that some studies found no evidence of rebound after varying durations of nightly or intermittent use of similar medications (zolpidem) for up to six months, while others reported evidence of rebound primarily limited to the first night following discontinuation 2

Important Considerations

• The risk-benefit profile of zopiclone for long-term use remains unclear, as most studies focus on short-term treatment 4
• Tolerance to the effects of zopiclone was not observed in short-term clinical trials (≤4 weeks), but data from longer-term studies are conflicting 4
• While the potential for rebound insomnia exists, reports of clinically significant rebound insomnia after zopiclone withdrawal are relatively rare in the literature 6
• The risk of developing dependence appears low with zopiclone when used as recommended, though the potential for abuse should be considered in patients with a history of substance use disorders 3, 6