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Background There is growing evidence of harm associated with trazodone and nonbenzodiazepine sedative hypnotics (e.g., zopiclone); however, their comparative risk of harm is unknown. Methods We conducted a retrospective cohort study with linked health administrative data, which enrolled older ( ≥66 years old) nursing home residents living in Alberta, Canada, between December 1, 2009, and December 31, 2018; the last followup date was June 30, 2019. We compared the rate of injurious falls and major osteoporotic fractures (primary outcome) and all-cause mortality (secondary outcome) within 180 days of first prescription of zopiclone or trazodone with cause-specific hazard models and inverse probability of treatment weights to control for confounding; primary analysis was intention-totreat and secondary analysis was per-protocol (i.e., residents censored if dispensed the other exposure drug). Results Our cohort included 1,403 residents newly dispensed trazodone and 1,599 residents newly dispensed zopiclone. At cohort entry, the mean resident age was 85.7 (standard deviation [SD] 7.4), 61.6% were female, and 81.2% had dementia. New zopiclone use was associated with similar rates of injurious falls and major osteoporotic fractures (intention-to-treat-weighted hazard ratio 1.15, 95% confidence interval [CI] 0.90-1.48; perprotocol-weighted hazard ratio 0.85, 95% CI 0.60-1.21) and all-cause mortality (intention-to-treat-weighted hazard ratio 0.96, 95% CI 0.79-1.16; per-protocol-weighted hazard ratio 0.90, 95% CI 0.66-1.23) compared to trazodone. Conclusions Zopiclone was associated with a similar rate of injurious falls, major osteoporotic fractures, and all-cause mortality compared to trazodone--suggesting one medication should not be used in lieu of the other. Appropriate prescribing initiatives should also target zopiclone and trazodone. [ABSTRACT FROM AUTHOR]

Background and Objective: Lemborexant is a dual orexin receptor antagonist recently approved in the USA, Japan, and Canada for the treatment of adults with insomnia. Because some pharmacotherapy for insomnia causes respiratory depression, this study assessed the effects of lemborexant treatment on respiratory safety parameters. Methods: This single-dose, randomized, double-blind, placebo-controlled, three-period crossover study enrolled healthy adult and elderly subjects (n = 17). Subjects were randomized to one of three treatment sequences, each consisting of three treatment periods in which they received a single dose of placebo, lemborexant 10 mg, or lemborexant 25 mg. Each treatment period was separated by a washout period of at least 14 days. Assessments included pharmacodynamic respiratory parameters (peripheral capillary oxygen saturation (SpO2) and apnea–hypopnea index (AHI)) and safety. Results: There were no significant differences for either dose of lemborexant versus placebo in mean peripheral capillary oxygen saturation (SpO2; least squares mean (LSM) difference (95% confidence interval (CI)): lemborexant 10 mg, −0.36 (−0.78 to 0.07); lemborexant 25 mg, − 0.29 (− 0.72 to 0.14)) or AHI (LSM difference (95% CI): lemborexant 10 mg, 0.52 (− 1.72 to 2.76); lemborexant 25 mg, − 1.16 (− 3.40 to 1.08)) during sleep. Additionally, significant differences were not observed for the percentage of total sleep during which SpO2 was < 85% (LSM difference (95% CI): lemborexant 10 mg, 0.004 (− 0.058 to 0.067); lemborexant 25 mg, 0.044 (− 0.018 to 0.107)) or < 80% (LSM difference (95% CI): lemborexant 10 mg, 0.001 (− 0.002 to 0.005); lemborexant 25 mg, 0.002 (−0.001 to 0.006)) for either lemborexant dose versus placebo. There was also no significant difference for lemborexant 10 mg versus placebo, for which SpO2 was < 90% during total sleep time (LSM difference (95% CI): 0.185 (− 0.034 to 0.405)). Conclusion: Overall, lemborexant at recommended doses did not have a negative effect on mean SpO2 or AHI and was well tolerated in this cohort of healthy subjects. Plain Language Summary: Insomnia is a sleep disorder in which people have trouble falling asleep or staying asleep, or both. People can take prescription medicines to help improve sleep, but these drugs can have side effects including making breathing more difficult during sleep. We looked at a new medicine for insomnia, lemborexant, and with the aim of finding out how it affects breathing during sleep and if there were any side effects. A group of 17 healthy adult and elderly people took a normal or high dose of lemborexant or a placebo that did not contain active medicine. Researchers measured people's breathing while they slept. We found that lemborexant did not change the amount of oxygen in people's blood during sleep, and that lemborexant did not cause people to have shallow breathing or to have brief pauses in their breathing. People who took lemborexant reported few side effects and these were all mild. In this study, lemborexant was well tolerated in healthy adults and elderly people and did not make breathing more difficult during sleep. [ABSTRACT FROM AUTHOR]

Background Utilization of psychotropic medications among the elderly has garnered attention due to concerns about safety and degree of efficacy, but may be used differently across regions. Methods We conducted a cross-sectional study of all antipsychotic, benzodiazepine, and trazodone prescriptions dispensed to seniors (≥ 65 years) leveraging IQVIA (Durham, NC) GPM data in 2013. We report the units dispensed (per 100 seniors) by province. Results Nationally, on average, 26,210 units of antipsychotics, 24,257 of benzodiazepines, and 7,519 of trazodone were dispensed in 2013 for every 100 seniors; reports varied across Canada. The rate of antipsychotic and benzodiazepine prescribing was highest in New Brunswick (AP: 35,375 units per 100, BZD: 43,989 units per 100), and lowest in Newfoundland & Labrador for antipsychotics (20,974 per 100) and Saskatchewan for benzodiazepines (12,692 per 100). Trazodone unit dispensation rates were highest in Nova Scotia (9,164 per 100) and lowest in Newfoundland & Labrador (2,968 per 100). Conclusions There is considerable geographic variation in the prescribing patterns of antipsychotics, benzodiazepine, and trazodone. This study serves as the first step in understanding these differences, while future work is needed to develop regionspecific strategies to optimize the prescribing of psychotropic medications to older Canadian adults. [ABSTRACT FROM AUTHOR]