Clinical Cases Podcast Series-FREE NO CME-2017 Bzd and Z-drug Review

2017 Bzd and Z-drug Review
Pdf Summary
This 2017 narrative review summarizes epidemiologic and experimental evidence on major adverse outcomes linked to benzodiazepines and non-benzodiazepine hypnotics (“Z-drugs” such as zolpidem, zopiclone, zaleplon, eszopiclone). It highlights that these drugs are effective sedative-hypnotics but have important safety concerns.<br /><br />The strongest and most causally supported harms are motor vehicle accidents and falls/fractures. Experimental driving studies using standardized deviation of lateral position (SDLP) show dose- and half-life–dependent impairment with benzodiazepines, and significant residual impairment with zopiclone (up to ~11 hours). Epidemiologic meta-analyses generally find increased crash risk with benzodiazepines (roughly 40–80% higher odds; higher for fatal crashes), with more limited but concerning evidence for Z-drugs (notably zolpidem in several studies). For falls and fractures, evidence consistently indicates increased risk largely through psychomotor and balance impairment; meta-analyses estimate benzodiazepines raise fracture risk modestly (about 13–30%), while zolpidem studies suggest potentially higher risk, though heterogeneity and confounding may inflate estimates. Risk appears greater with higher doses and during early treatment.<br /><br />Regarding overdose, benzodiazepines alone rarely cause fatal respiratory depression, but combined use with opioids and/or alcohol markedly increases morbidity and mortality; U.S. data show rising overdose deaths involving benzodiazepines, often with opioids.<br /><br />For newer proposed associations—dementia, infections (e.g., pneumonia/influenza-like illness), respiratory disease exacerbations (COPD/asthma), pancreatitis, and cancer—the review finds evidence is suggestive but inconsistent and vulnerable to bias (e.g., confounding by indication, protopathic/reverse-causation). The authors conclude that causality is clear for accidents and falls/fractures, but not established for the other outcomes, and call for better prospective studies and mechanistic research to clarify risks and guide safer use.
Keywords
benzodiazepines
Z-drugs
zolpidem
motor vehicle accidents
falls
fractures
overdose
dementia
COPD
psychomotor impairment