What are the long-term implications of zopiclone (nonbenzodiazepine hypnotic agent) use?

From the Guidelines

Zopiclone's long-term use is associated with significant risks, including physical dependence, cognitive impairment, and increased risk of falls and accidents, and therefore should be used at the lowest effective dose for the shortest duration possible, ideally not exceeding 2-4 weeks, as recommended by recent guidelines 1. The potential long-term implications of zopiclone use include:

• Physical dependence and tolerance, requiring higher doses for the same effect
• Withdrawal symptoms upon discontinuation
• Cognitive impairment, including memory problems and daytime drowsiness
• Increased risk of falls and accidents, particularly in older adults
• Potential associations with dementia with prolonged use, though research is ongoing
• Psychological dependence, making it difficult to stop despite negative consequences These concerns stem from zopiclone's mechanism as a non-benzodiazepine hypnotic that enhances GABA activity in the brain, which can lead to adaptive changes with prolonged exposure. Key considerations for prescribing zopiclone include:
• Using the lowest effective dose, typically 7.5mg for adults and 3.75mg for elderly patients
• Limiting treatment duration to the shortest possible time, ideally not exceeding 2-4 weeks
• Counseling patients on the potential risks and benefits of zopiclone use
• Considering non-pharmacological approaches, such as cognitive behavioral therapy for insomnia (CBT-I), as first-line treatments for persistent sleep problems. Recent guidelines and systematic reviews support these recommendations, highlighting the importance of careful consideration and caution when prescribing zopiclone for long-term use 1.

From the Research

Long Term Implications of Zopiclone

• The long term implications of zopiclone are not well established, as it is indicated for short term use and should not be prescribed for more than 4 weeks 2, 3.
• Studies have shown that zopiclone is effective and well tolerated in the short term treatment of insomnia, with a low propensity for rebound insomnia and dependence 2, 3.
• However, the risk-benefit profile of zopiclone in long term use remains unknown, and potential differences between zopiclone and benzodiazepines in terms of rebound insomnia and dependence liability may have little clinical relevance in the context of short term intermittent use 3.
• Cognitive behavioral therapy (CBT) has been shown to be an effective alternative to zopiclone for the treatment of chronic insomnia, with similar or superior efficacy and longer lasting effects 4, 5.
• CBT has also been shown to improve sleep quality, reduce symptoms of depression and anxiety, and improve sleep hygiene and dysfunctional beliefs about sleep 4, 5.
• The combination of CBT and pharmacological treatment, such as eszopiclone, may be more effective than pharmacological treatment alone for the treatment of sleep disorders in certain patient populations 6.

Comparison with Other Treatments

• Zopiclone has been compared to other hypnotic agents, including benzodiazepines, and has been shown to be at least as effective, with a similar tolerability profile 2, 3.
• CBT has been compared to zopiclone and other pharmacological treatments, and has been shown to be an effective and durable treatment for chronic insomnia 4, 5.
• The combination of CBT and pharmacological treatment may be more effective than pharmacological treatment alone for certain patient populations, such as those transferred out of the intensive care unit 6.

Patient Populations

• Zopiclone is well tolerated in both elderly and younger patients with insomnia 2, 3.
• CBT has been shown to be effective in older adults with chronic primary insomnia, with improved sleep efficiency and reduced symptoms of depression and anxiety 5.
• The combination of CBT and pharmacological treatment may be effective in patient populations with sleep disorders, such as those transferred out of the intensive care unit 6.