Nonbenzodiazepine Sedative Hypnotics and Risk of Fall-Related Injury

The objective of this study was to test the hypothesis that use of zolpidem, eszopiclone, and zaleplon would be associated with increased risk of traumatic brain injury (TBI) and hip fracture. We conducted a case-crossover study on a 5% random sample of Medicare beneficiaries age 65 y or older hospitalized with either TBI (n = 15,031) or hip fracture (n = 37,833) during 2007–2009. Use of zolpidem, eszopiclone, or zaleplon during the 30-day period prior to injury hospitalization was compared to use during four control periods at 3, 6, 9, and 12 mo prior to injury. The primary outcome was hospitalization for TBI or hip fracture. Zolpidem use during the month prior to injury was associated with increased risk of TBI (odds ratio [OR] 1.87; 95% confidence interval [CI] 1.56, 2.25); however, eszopiclone use during the same period was not associated with increased risk (OR 0.67; 95% CI 0.40, 1.13). Zolpidem use during the month prior to injury was associated with increased risk of hip fracture (OR 1.59; 95% CI 1.41, 1.79); however, eszopiclone use during the same period was not associated with increased risk (OR 1.12; 95% CI 0.83, 1.50). Analysis of zaleplon use in the month prior to injury was limited by low drug utilization but was not associated with increased risk of TBI (OR 0.85; 95% CI 0.21, 3.34) or hip fracture (OR 0.92; 95% CI 0.40, 2.13) in this study. For the treatment of insomnia in older adults, eszopiclone may present a safer alternative to zolpidem, in terms of fall-related injuries. Sleep complaints represent a major public health concern. In spite of documented risks of adverse events, the most commonly employed treatment for insomnia remains sedative hypnotic therapy. In the current study of Medicare beneficiaries, zolpidem, but not eszopiclone, was associated with increased risk of hip fracture and TBI resulting in hospitalization. Whereas a growing body of evidence documents risks associated with zolpidem, these are the first data to document a differential risk between NBSHs. Use of eszopiclone may present a safer alternative to zolpidem for the treatment of insomnia, in terms of fall-related injury. Additional studies are needed to verify the relationships between specific NBSH drugs with fall-related outcomes and to consider alternative insomnia management strategies.