Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research

Abstract

Various adverse events resulting from, or associated with, benzodiazepine and/or Z-drug use have been extensively reported on and discussed in great detail within the biomedical literature. It is widely accepted that motor vehicle accidents and falls leading to fractures in older adults are major adverse events that have been shown to occur more frequently in users of sedative-hypnotic medication, especially of the benzodiazepine and related Z-drug variety. However, the last few years have seen increasing reports in the literature raising the issue of benzodiazepine and Z-drug exposure in the development of other serious medical issues including dementia, infections, respiratory disease exacerbation, pancreatitis, and cancer. This article provides an overview and interpretation on the current state of evidence regarding each of these associations and proposes what gaps in the evidence for drug-exposure–harm associations need to be addressed in the future for the purpose of evaluating causality of harm as it relates to these drugs.

Medicines associated with dependence or withdrawal: a mixed-methods public health review and national database study in England

“…these medicines were developed with the aim of preventing the over-sedation and daytime sleepiness associated with benzodiazepines, and were initially believed to carry a low risk of dependence. 14 Antidepressants are not associated with a risk of dependence, are used long-term for severe depression, and can bring transformative clinical benefit. [15][16][17] However, antidepressants have become controversial, with claims that they have minimal efficacy and can be harmful.…”

Patient‐reported factors associated with the desire to continue taking sleep‐inducing drugs after hospital discharge: A survey of older adults

“…A review based on epidemiological research found an overwhelming degree of evidence that benzodiazepines and Z‐drugs cause fatal and nonfatal motor vehicle accidents, fractures, and cognitive dysfunction and, at least, weak evidence that these drugs cause dementia. And even if clinical doubt persists regarding the new safety accusations, such as dementia, pancreatitis, or cancer, the use of these drugs, especially in older persons, needs particular caution. Glass et al and Treves et al come to the same conclusion, namely, that for persons over 60, the benefits of sedatives and hypnotics may not justify the increased risk.…”

“…[4][5][6][7] In Germany, it is estimated that 1.2 to 1.5 million of its 82 million citizens are dependent upon tranquilizers and sleep-inducing drugs, especially older people. 8 A review based on epidemiological research 9 found an overwhelming degree of evidence that benzodiazepines and Z-drugs cause fatal and nonfatal motor vehicle accidents, fractures, and cognitive dysfunction and, at least, weak evidence that these drugs cause dementia. And even if clinical doubt persists regarding the new safety accusations, such as dementia, pancreatitis, or cancer, 9 the use of these drugs, especially in older persons, needs particular caution.…”

Concomitant use of benzodiazepines and opioids in community‐dwelling older people with or without Alzheimer's disease—A nationwide register‐based study in Finland

“…[1][2][3] The use of BZDRs in older people is problematic because they are associated with several risks, such as sedation, dependence, falls, and fractures. 4 In general, BZDRs are approved for short-term use (less than 2-4 weeks) and not recommended for long-term use. 5 In older people, even short-term use of BZDRs poses risks due to sedation and falls resulting in fractures.…”