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Concept: Zaleplon

249

Knowledge regarding whether benzodiazepines and similarly acting non-benzodiazepines (Z-drugs) are associated with an increased risk of pneumonia among older adults is lacking. We sought to investigate this association among community-dwelling adults with Alzheimer disease, a condition in which both sedative/hypnotic use and pneumonia are common.

Concepts: Alzheimer's disease, Pneumonia, Benzodiazepine, Zaleplon, Zolpidem

188

Hip fractures in the older person lead to an increased risk of mortality, poorer quality of life and increased morbidity. Benzodiazepine (BNZ) use is associated with increased hip fracture rate, consequently Z-drugs are fast becoming the physician’s hypnotic prescription of choice yet data on their use is limited. We compared the risk of hip fracture associated with Z-drugs and BNZ medications, respectively, and examined if this risk varied with longer-term use.

Concepts: Osteoporosis, Pharmacology, Bone fracture, Benzodiazepine, Barbiturate, Hypnotic, Zaleplon, Zolpidem

13

Despite cautions by professional associations, benzodiazepines (BZD) and Z hypnotics (BZD/Z) are widely prescribed to older adults who are particularly susceptible to insomnia and anxiety, but who are also more sensitive to drugs adverse events. In this study, we assessed the prescription of BZD/Z drugs in a sample of older adults (≥65) who presented for emergency care after a fall.

Concepts: Benzodiazepine, Hypnotic, Insomnia, Flunitrazepam, Zaleplon, Triazolam, Nonbenzodiazepine, Temazepam

6

Long-term sedative use is prevalent and associated with significant morbidity, including adverse events such as falls, cognitive impairment, and sedation. The development of dependence can pose significant challenges when discontinuation is attempted as withdrawal symptoms often develop. We conducted a scoping review to map and characterize the literature and determine opportunities for future research regarding deprescribing strategies for long-term benzodiazepine and Z-drug (zopiclone, zolpidem, and zaleplon) use in community-dwelling adults.

Concepts: Physical dependence, Withdrawal, Benzodiazepine, Hypnotic, Zaleplon, Zolpidem, Zopiclone, Nonbenzodiazepine

4

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.

Concepts: Benzodiazepine, Hypnotic, Insomnia, Zaleplon, Zolpidem, Zopiclone, Nonbenzodiazepine, Z-drug

4

Use of sedatives may increase risk of death in opioid users. The aim of the study was to assess whether prescription of sedatives may be associated with mortality in patients in opioid maintenance treatment.

Concepts: Cohort study, Cohort, Actuarial science, Midazolam, Alprazolam, Medical prescription, Benzodiazepine, Zaleplon

3

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.

Concepts: Pharmacology, Epidemiology, Disease, Infectious disease, Benzodiazepine, Zaleplon, Sedative, Zolpidem

3

The aim of our study was to investigate the risk of any, ischemic, and hemorrhagic stroke associated with incident benzodiazepine and related drug (BZDR) use among community-dwelling individuals with Alzheimer’s disease (AD). Data from the MEDALZ cohort including all community-dwelling persons newly diagnosed with AD between 2005 and 2011 in Finland were utilized. Incident BZDR users were identified with a 1-year washout period for previous use. Persons with a previous stroke were excluded, resulting in a final study sample of 45 050 individuals. Incident any, ischemic, and hemorrhagic strokes were identified from the Hospital Discharge and Causes of Death registers. The risk of stroke between time on BZDRs was compared with nonuse time with Cox proportional hazard models. During the follow-up, 21.9% (N=9879) of persons started BZDR use. Compared with nonuse, BZDR use was associated with an increased risk of any stroke [adjusted hazard ratio (aHR): 1.21; 95% confidence interval (CI): 1.04-1.40] and ischemic stroke (aHR: 1.21; 95% CI: 1.02-1.44), but the association between BZDR use and hemorrhagic stroke did not reach significance (aHR: 1.26; 95% CI: 0.91-1.74). Z-drug use was associated with a similar risk as benzodiazepine use. In conclusion, BZDR use was associated with an increased risk of stroke among older individuals with AD.

Concepts: Epidemiology, Sample size, Proportional hazards models, Stroke, Dementia, Benzodiazepine, Zaleplon, Long-term effects of benzodiazepines

2

Benzodiazepines are effective medicines for insomnia and anxiety but are commonly used beyond recommended treatment time frames, which may lead to adverse drug events. The aim of this systematic review was to critically evaluate the success of interventions used to reduce benzodiazepines and ‘Z-drug’ use, and the impact of these interventions on clinical outcomes in older adults.

Concepts: Pharmacology, Adverse drug reaction, Benzodiazepine, Hypnotic, Insomnia, Zaleplon, Zolpidem, Zopiclone

2

IMPORTANCE It is important to understand the relationship between sleep medication use and injurious falls in nursing home residents. OBJECTIVE To conduct a case-crossover study to estimate the association between nonbenzodiazepine hypnotic drug use (zolpidem tartrate, eszopiclone, or zaleplon) and the risk for hip fracture among a nationwide sample of long-stay nursing home residents, overall and stratified by individual and facility-level characteristics. DESIGN AND SETTING Case-crossover study performed in an academic research setting. PARTICIPANTS The study participants included 15 528 long-stay US nursing home residents 50 years or older with a hip fracture documented in Medicare Part A and Part D fee-for-service claims between July 1, 2007, and December 31, 2008. MAIN OUTCOME MEASURES Odds ratios (ORs) of hip fracture were estimated using conditional logistic regression models by comparing the exposure to nonbenzodiazepine hypnotic drugs during the 0 to 29 days before the hip fracture (hazard period) with the exposure during the 60 to 89 and 120 to 149 days before the hip fracture (control periods). Analyses were stratified by individual and facility-level characteristics. RESULTS Among the study participants, 1715 (11.0%) were dispensed a nonbenzodiazepine hypnotic drug before the hip fracture, with 927 exposure-discordant pairs included in the analyses. The mean (SD) age of participants was 81.0 (9.7) years, and 77.6% were female. The risk for hip fracture was elevated among users of a nonbenzodiazepine hypnotic drug (OR, 1.66; 95% CI, 1.45-1.90). The association between nonbenzodiazepine hypnotic drug use and hip fracture was somewhat greater in new users (OR, 2.20; 95% CI, 1.76-2.74) and in residents with mild vs moderate to severe impairment in cognition (OR, 1.86 vs 1.43; P = .06), with moderate vs total or severe functional impairment (OR, 1.71 vs 1.16; P = .11), with limited vs full assistance required with transfers (OR, 2.02 vs 1.43; P = .02), or in a facility with fewer Medicaid beds (OR, 1.90 vs 1.46; P = .05). CONCLUSIONS AND RELEVANCE The risk for hip fracture is elevated among nursing home residents using a nonbenzodiazepine hypnotic drug. New users and residents having mild to moderate cognitive impairment or requiring limited assistance with transfers may be most vulnerable to the use of these drugs. Caution should be exercised when prescribing sleep medications to nursing home residents.

Concepts: Benzodiazepine, Hypnotic, Insomnia, Zaleplon, Zolpidem, Zopiclone, Nonbenzodiazepine, Eszopiclone