Association of orexin receptor antagonists with falls during hospitalization

Sogawa, Rintaro; Emoto, Akiko; Monji, Akira; Miyamoto, Yuki; Yukawa, Misako; Murakawa-Hirachi, Toru; Tagomori, Yasuhiro; Kawasaki, Mikiko; Kimura, Shinya; Shimanoe, Chisato

doi:10.1111/jcpt.13619

Cited by 16 publications

(12 citation statements)

References 20 publications

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“…Falls, a common concern in the older population, which may be precipitated by some hypnotic drugs prescribed for insomnia [ 25 , 50 , 51 ], were infrequent. Specifically, the number of falls was numerically lower in patients receiving daridorexant (either dose) than in those receiving placebo, as suggested with other DORAs [ 52 ]. Daridorexant, like other approved DORAs, has been designated as a schedule IV-controlled substance by the US Drug Enforcement Agency.…”

Section: Discussionmentioning

confidence: 79%

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

et al. 2022

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Background and ObjectiveThe dual orexin receptor antagonist daridorexant, studied in two phase III trials, dose-dependently improved objective and subjective sleep variables and daytime functioning in adults with insomnia. Because treatment of insomnia in older adults is challenging and has limited options, the purpose of the current analysis was to further analyse the phase III trial studying the higher doses of daridorexant, those that showed efficacy (daridorexant 50 mg, daridorexant 25 mg and placebo, nightly for 3 months), and compare the safety and efficacy of daridorexant in patients aged ≥ 65 ('older adults') to those aged < 65 years ('younger adults'). Methods Analyses by age (≥ 65 years, n = 364; < 65 years, n = 566) were performed on data from the randomised, doubleblind, placebo-controlled Trial 1 in adult patients with insomnia (NCT03545191). Efficacy endpoints included a change from baseline at month 1 and month 3 in polysomnography-measured wake after sleep onset (WASO) and latency to persistent sleep (LPS), self-reported total sleep time (sTST) and daytime functioning assessed using the validated Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Safety endpoints included adverse events and the Visual Analog Scale for morning sleepiness. Results At baseline, mean [standard deviation] WASO was numerically greater (110 [39] vs 92 [38] min) in older than younger adults, while LPS was comparable (~ 65 min). Mean baseline IDSIQ total and all domain scores were numerically lower (i.e. better) in older adults. Daridorexant caused similar reductions in WASO and LPS, and similar increases in sTST, from baseline, in both age groups; improvements were numerically greater with daridorexant 50 mg than 25 mg. At month 3, daridorexant 50 mg, compared with placebo, decreased WASO by a least-squares mean of 19.6 (95% confidence interval 9.7, 29.5) in older patients versus 17.4 min (10.7, 24.0) in younger patients and decreased LPS by a least-squares mean of 14.9 (7.5, 22.3) in older patients versus 9.7 min (3.7, 15.7) in younger patients. Daridorexant 50 mg increased sTST from baseline to month 3 by a least-squares mean of 59.9 (49.6, 70.3) in older patients versus 57.1 min (48.9, 65.3) in younger patients. Daridorexant 50 mg progressively improved IDSIQ total and domain scores from week 1 onwards similarly in both groups; daridorexant 25 mg improved IDSIQ scores, but only in younger adults. In both age groups, in comparison with placebo, the overall incidence of adverse events was comparable, and there were fewer falls on daridorexant. Daridorexant improved Visual Analog Scale morning sleepiness in both groups; daridorexant 50 mg increased the mean (standard deviation) Visual Analog Scale morning sleepiness score by 15.9 (20.7) in older adults and by 14.9 (18.7) in younger adults from baseline to month 3. In older adults, there was one case of sleep paralysis, and no cases of narcolepsy, cataplexy, or complex sleep behaviour. Conclusions In older patients with insomnia, as in younger patients, the effi...

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Section: Discussionmentioning

confidence: 79%

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

et al. 2022

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“…As in our previous studies, both benzodiazepines and non-benzodiazepines were included among hypnotic medications, except for melatonin receptor agonists and orexin receptor antagonists because these drugs have fewer side effects that cause falls. 27 , 28 If an inpatient experiences a fall, a nurse in charge of the patient or who finds the patient completes an incident/accident report. The number of falls was calculated using these reports.…”

Section: Methodsmentioning

confidence: 99%

History of Falls and Bedriddenness Ranks are Useful Predictive Factors for in-Hospital Falls: A Single-Center Retrospective Observational Study Using the Saga Fall Risk Model

Hirata¹,

Tago²,

Katsuki³

et al. 2022

IJGM

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In our former study, we had validated the previously developed predictive model for in-hospital falls (Saga fall risk model) using eight simple factors (age, sex, emergency admission, department of admission, use of hypnotic medications, history of falls, independence of eating, and Bedriddenness ranks [BRs]), proving its high reliability. We found that only admission to the neurosurgery department, history of falls, and BRs had significant relationships with falls. In the present study, we aimed to clarify whether each of these three items had a significant relationship with falls in a different group of patients. Methods: This was a single-center based, retrospective study in an acute care hospital in a rural city of Japan. We enrolled all inpatients aged 20 years or older admitted from April 2015 to March 2018. We randomly selected patients to fulfill the required sample size. We performed multivariable logistic regression analysis using forced entry on the association between falls and each of the eight items in the Saga fall risk model 2. Results: A total of 2932 patients were randomly selected, of whom 95 (3.2%) fell. The median age was 79 years, and 49.9% were men. Multivariable analysis showed that female sex (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.39-0.93, p = 0.022), having a history of falls (

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“…Although some countries offer melatonin as an over-the-counter drugs or supplements, it is not available in Japan. Previous studies have shown that ramelteon, a melatonin receptor agonist, does not have a significant effect on falls or fractures [ 15 – 17 ]. However, we found that melatonin receptor agonists increased the risk of femoral fractures in patients with PD, which may be attributed to physician bias, where melatonin receptor agonists are prescribed to patients who are at a high risk of falls because these drugs are less likely than benzodiazepines and non-benzodiazepines to cause falls.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study in older adults showed that suvorexant, an orexin receptor antagonist, is associated with a lower risk of falls than placebo; however, somnolence was more common with suvorexant than with placebo [ 20 ]. Another previous study demonstrated that lemborexant, another orexin receptor antagonist that was approved in Japan in 2020, significantly lowered the risk of falls [ 17 ]. In contrast, we found that orexin receptor antagonists did not increase the risk of injuries.…”

Section: Discussionmentioning

confidence: 99%

Hypnotics and injuries among older adults with Parkinson’s disease: a nested case–control design

Fujita

Babazono

et al. 2023

BMC Geriatr

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Background Patients with Parkinson’s disease often experience sleep disorders. Hypnotics increase the risk of adverse events, such as injuries due to falls. In this study, we evaluated the association between hypnotics and injuries among older adults with Parkinson’s disease. Methods The study used a nested case–control design. The participants were 5009 patients with Parkinson’s disease aged ≥ 75 years based on claims data between April 2016 and March 2019 without prescription hypnotics 1 year before the study started. Hypnotics prescribed as oral medications included benzodiazepines, non-benzodiazepines, orexin receptor antagonists, and melatonin receptor agonists. The incidences of outcomes, including injuries, fractures, and femoral fractures, were determined. Each case had four matched controls. Conditional logistic regression analyses were performed to calculate the odds ratios and 95% confidence intervals for the number of hypnotics taken per day for each type of hypnotic. Results The proportion of participants taking at least one type of hypnotic was 18.6%, with benzodiazepines being the most common. The incidence of injuries, fractures, and femoral fractures was 66.7%, 37.8%, and 10.2%, respectively. Benzodiazepines significantly increased the risk of injuries (odds ratio: 1.12; 95% confidence interval: 1.03–1.22), and melatonin receptor agonists significantly increased the risk of femoral fractures (odds ratio: 2.84; 95% confidence interval: 1.19–6.77). Conclusions Benzodiazepines and non-benzodiazepines, which are not recommended according to current guidelines, were the most prevalent among older adults with Parkinson’s disease. Benzodiazepines significantly increased the risk of injuries, and melatonin receptor agonists significantly increased the risk of femoral fractures.

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Association of orexin receptor antagonists with falls during hospitalization

Cited by 16 publications

References 20 publications

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial

History of Falls and Bedriddenness Ranks are Useful Predictive Factors for in-Hospital Falls: A Single-Center Retrospective Observational Study Using the Saga Fall Risk Model

Hypnotics and injuries among older adults with Parkinson’s disease: a nested case–control design

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