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Nonbenzodiazepine hypnotic drugs are associated with increased fractures in older adults
Clinical Question
Are zolpidem, zopiclone, eszopiclone and zaleplon—nonbenzodiazepine hypnotics that are also known as z-drugs—associated with harms in older adults?
Bottom line
Among 14 studies reporting on harms of taking so-called z-drugs, the data show an association with higher fracture and injury risk. 2a-
Reference
Study design: Meta-analysis (other)
Funding: Self-funded or unfunded
Setting: Various (meta-analysis)
Synopsis
These authors searched 2 databases and a clinical trials registry to identify studies of nonbenzodiazepine hypnotic drugs that included an assessment of fractures, falls, and injuries. These hypnotic drugs—zolpidem (Ambien), zopiclone (Zimovane, Imovane), eszopiclone (Lunesta), and zaleplon (Sonata, Starnoc, and Andante)—are sometimes called z-drugs. The authors also scanned the reference lists of retrieved studies. Their search included randomized trials, as well as observational studies. Two investigators independently determined study eligibility and resolved disagreements by discussion and consensus. Ultimately, they included 14 studies with more than 800,000 patients. All of the studies were observational: 10 studies (> 830,000 patients) reported on fractures, 3 studies (> 19,000 patients) reported on falls, and 2 studies (> 160,000) reported on injuries. Patients taking z-drugs were 1.6 times more likely to experience a fracture (95% CI 1.4 - 1.9), but these data demonstrated high levels of heterogeneity. Patients taking z-drugs were not at a statistically significant increased risk of falls, but these data, too, were quite heterogeneous. Finally, patients taking zolpidem (the only drug studied for differences in injury rates) were twice as likely as those not taking it to have injuries (odds ratio 2.05; 1.95 - 2.15) with no evidence for statistical heterogeneity. The results didn't vary when taking various subgroup analyses into account.
Reviewer
Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI
Comments
This study should be in the public press ...
Interesting and not surprising. However, I wonder if clinical judgement is required in elderly patients who don’t sleep an in whom these meds work. There is evidence that insomnia and fatigue also increase the risk of falls and injuries. I find that some elderly people (actually many patients) are not amenable to CBT for insomnia. Also, how many of us have access to effective CBT. It is a precious and not very accessible resource and often not covered by OHIP.
Many CBT practioners know little about CBT for insomnia. Where does this leave us with this problem.
Title is inaccurate and misleading, once again, due to a probable lack of clinical knowledge outside of statistics. "Nonbenzodiazepine hypnotic drugs are associated with increased fractures in older adults"
1. There are several other "non-benzodiazepine hypnotic drugs" than the "Z' drugs assessed; this work did not study them.
2. The risk of fractures with "non-benzodiazepine hypnotic drugs" was not studied and may be the same or worse than the "Z' drugs assessed.
I will stop routine refill of zopiclone in the elderly
Incongruous relationship
That there are increased fractures in those taking z-drugs but not statistically increased falls begs the question as to how those fractures occur if not through a fall.
I use these hypnotics cautiously and have not seen fractures or falls in these patients. However my group may be younger, especially newly menopausal women.
Good poem