Z-drugs and risk for falls and fractures in older adults-a systematic review and meta-analysis

Objective: zolpidem, zopiclone, eszopiclone and zaleplon, also known as 'Z-drugs', are commonly used as alternatives to benzodiazepines (BZDs) to treat insomnia. Z-drugs are often perceived as safer than BZDs. We conducted a systematic review and meta-analysis evaluating the association between Z-drugs and fracutres, falls and injuries. Methods: a systematic review was performed using MEDLINE, EMBASE and ClinicalTials.gov. Pooled effect-sizes were calculated comparing Z-drugs users with non-users, using fixed and random-effect models with corresponding 95% confidence of intervals (CI). Results: we identified 14 eligible studies reporting on the association between Z-drugs and outcomes of interest. Z-Drugs were associated with a statistically significant increased risk for fractures, with evidence of considerable heterogeneity (OR = 1.63; 95% CI: 1.42-1.87; I2 = 90%; n = 830,877). Likewise, there was a trend suggesting a 2-fold increase in the odds for falls, however, this result was not statistically significant and there was evidence of considerable heterogeneity (OR = 2.40; 95% CI: 0.92-6.27; I2 = 95%; n = 19,505). In an analysis assessing the risk for injuries following exposure to zolpidem we found a statistically significant increased risk of injuries, with no evidence of heterogeneity (OR = 2.05; CI 95%: 1.95-2.15; I2 = 0; n = 160,502). Results were similar in sensitivity analyses, including analyses restricted to studies of high-quality, studies with control groups suffering from insomnia, and with specific Z-drugs. Conclusion: our results indicate that Z-drugs are associated with an increased risk for fractures, and suggest a possible increased risk for falls and injuries as well. However, studies included were observational and susceptible to confounding. Physicians should consider these potential risks before prescribing these medications in older adults.