Is there a risk of dementia associated with zopiclone (nonbenzodiazepine hypnotic agent)?

From the Guidelines

There is a potential risk of dementia associated with zopiclone use, particularly with long-term use, as suggested by observational studies 1. Zopiclone belongs to a class of medications called non-benzodiazepine hypnotics (Z-drugs) that work on GABA receptors in the brain to induce sleep. Some observational studies have suggested an association between regular use of these sleep medications and increased risk of developing dementia, though the evidence is not conclusive and causality has not been firmly established. The risk appears to be higher with prolonged use and higher doses. This potential risk is thought to be related to how these medications affect brain chemistry and cognitive function over time. For this reason, zopiclone is generally recommended only for short-term use (2-4 weeks maximum) to treat insomnia, as also advised in the management of chronic insomnia disorder and obstructive sleep apnea guidelines 1. If you need sleep medication for longer periods, discuss with your healthcare provider about the risks versus benefits and consider non-medication approaches to managing sleep problems, such as cognitive behavioral therapy for insomnia (CBT-I), sleep hygiene improvements, or addressing underlying conditions that may be causing sleep disturbances. Key points to consider:

• Zopiclone is a non-benzodiazepine hypnotic that can improve short-term sleep outcomes
• Long-term use of zopiclone may be associated with an increased risk of dementia
• The medication should be used at the lowest effective dose and for the shortest possible duration
• Non-medication approaches to managing sleep problems should be considered, especially for long-term management.

From the Research

Risk of Dementia with Zopiclone

• The association between zopiclone use and the risk of cognitive impairment or dementia has been investigated in several studies 2, 3, 4, 5, 6.
• A study published in 2021 found that benzodiazepine exposure density was an independent risk factor for cognitive impairment in middle-aged and older patients with chronic insomnia, but no correlation was found between zopiclone use and cognitive impairment 2.
• Another study published in 1998 found that zopiclone was generally at least as effective as benzodiazepines in the treatment of insomnia, and had a relatively low propensity to cause residual clinical effects, such as difficulty in waking or reduced morning concentration 3.
• A review of 15 years of clinical experience with zopiclone found that it was effective and well-tolerated in the treatment of insomnia, with a low risk of dependence and rebound insomnia 4.
• A meta-analysis published in 2014 found that zopiclone and zolpidem had medium effect sizes on measures of verbal memory, and that zolpidem also had a medium effect size on attention 6.
• However, none of the studies found a significant association between zopiclone use and an increased risk of dementia 2, 3, 4, 5, 6.

Cognitive Effects of Zopiclone

• Zopiclone has been found to have specific negative effects on cognitive function, including verbal memory and working memory 6.
• However, the effects of zopiclone on cognitive function are generally considered to be mild and short-term 3, 4.
• A study published in 2012 found that melatonergic drugs, such as ramelteon and agomelatine, may be effective in improving sleep quality and reducing the risk of cognitive impairment 5.