Association between Elimination Half-life of Benzodiazepines and Falls in the Elderly: A Meta-analysis of Observational Studies

Masudo, Chikako; Ogawa, Yukari; Yamashita, Naomi; Mihara, Kiyoshi

doi:10.1248/yakushi.18-00156

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…10,11 BZD/non-BZD is a risk factor for falls, cognitive impairment, and delirium. [12][13][14] It is reported that BZD/non-BZD could cause dependence within months, even with regular doses. 15 Additionally, another study reported that BZD/non-BZD can be reduced at a relatively high rate, discontinued, or switched to lemborexant, which is considered less risky.…”

Section: Discussionmentioning

confidence: 99%

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Reducing the use of psychotropics in a convalescent rehabilitation ward

Uematsu,

Tomita,

Obara

et al. 2023

Neuropsychopharm Rep

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AimsMany patients who are transferred to the convalescent rehabilitation ward of Kawasaki Kokoro Hospital (hereinafter, our hospital) are on psychotropics prescribed for delirium by their physicians at acute care hospitals. In this study, psychiatrists and pharmacists collaborated with rehabilitation physicians to reduce the use of psychotropics.MethodsThe basic information and psychotropics prescription statuses of 88 patients discharged from the convalescent rehabilitation ward of our hospital between April 1, 2021 and March 31, 2022 were derived from their medical records.ResultsAt admission, psychotropics were prescribed to 55 patients and the number of prescribed drugs was 2 (median). At discharge, psychotropics were prescribed to 41 patients and the number of prescribed drugs was 1 (median), showing a significant decrease (p < 0.05). Compared with those at admission, prescribed psychotropic doses at discharge were significantly higher for lemborexant but significantly lower for antipsychotics, benzodiazepine/nonbenzodiazepine hypnotics, antidepressants, suvorexant, ramelteon, and sodium valproate (p < 0.05).ConclusionsThese results suggest that it may be possible to reduce the types and doses of psychotropics prescribed at acute care hospitals in convalescent rehabilitation wards. However, further investigation is needed because the number of patients in this study was limited, and selection bias due to different patient characteristics cannot be ruled out.

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Section: Discussionmentioning

confidence: 99%

“…BZD/non‐BZD is a risk factor for falls, cognitive impairment, and delirium 12–14 . It is reported that BZD/non‐BZD could cause dependence within months, even with regular doses 15 .…”

Section: Discussionmentioning

confidence: 99%

Reducing the use of psychotropics in a convalescent rehabilitation ward

Uematsu,

Tomita,

Obara

et al. 2023

Neuropsychopharm Rep

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“…A meta-analysis of observational studies of older subjects aged ≥ 65 years previously suggested that benzodiazepine receptor agonists signi cantly increase fall incidence, regardless of the duration of drug action [15]. In older adults, blood levels of drugs may be increased because of the impairment of renal and hepatic function associated with physiological decline, which likely increases fall risk.…”

Section: Discussionmentioning

confidence: 99%

Association between nocturnal falls and hypnotic drug use in older patients at acute care hospitals

Oda

Takechi

Hirai

et al. 2023

Eur J Clin Pharmacol

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Purpose: Although hypnotic drug use is a known risk factor for falls, few reports have analyzed fall risk associated with individual hypnotic drugs after adjusting for confounding factors. Therefore, it remains unclear whether clinically prescribed benzodiazepine receptor agonist, melatonin receptor agonist, and/or orexin receptor antagonist use is safe in older patients. Here, we aim to assess the in uence of various hypnotic drugs on fall risk in older patients admitted to acute care hospitals.Methods: We investigated the relationship between nocturnal falls and sleeping pill use among 8,044 hospitalized patients aged > 65 years. We used a propensity score matching method to homogenize characteristics of patients with and without nocturnal falls (n = 145 patients in each group) using 24 extracted factors (excluding hypnotic drugs) as covariates.Results: Our analysis of fall risk for each hypnotic drug revealed that benzodiazepine receptor agonists were the only drugs signi cantly associated with falls, suggesting that use of the drugs is a risk factor for falls in older adults (p = 0.003). In addition, a multivariate analysis of 24 selected factors, excluding hypnotic drugs, revealed that patients with advanced recurrent malignancies were at greatest risk of experiencing falls (OR: 2.62; 95% CI: 1.23-5.60; p = 0.013).Conclusion: Benzodiazepine receptor agonists should be avoided in older hospitalized patients since they increase fall risk, with melatonin and orexin receptor antagonists used instead. Particularly, fall risk associated with hypnotic drugs should be considered in patients with advanced recurrent malignancies.

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“…As triazolam has a very short half-life of 2.9 h and the effect of carry-over to the next morning is considered small, it tends to be more commonly used on the elderly compared with long-acting benzodiazepines. However, it has also been reported that the occurrence risk of falls is the same regardless of half-life, or the presence or absence of a benzodiazepine skeleton [40]. Thus, there is no consensus on the effects of factors such as half-life on falls.…”

Section: Discussionmentioning

confidence: 99%

Appropriate use of triazolam in elderly patients considering a quantitative benefit-risk assessment based on real-world data with a modeling and simulation approach

Okada

Shoji

Nagai

2023

Preprint

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Background Triazolam is a typical drug commonly used in the elderly; however, there have been concerns about its adverse events resulting from age-related changes in physiological function anddrug interactions with concomitant drugs. Thus, updated information contributing to the appropriate use based on the latest pharmacokinetic and post-marketing surveillance methods, is needed. In this study, we evaluated the appropriate use of triazolam in the elderly by integrating real-world data with a modeling and simulation approach. Methods The occurrence risk of adverse events in the elderly was evaluated using the spontaneous adverse event reporting regulatory databases from Japan and the United States. Information on drug concentrations and reactions was extracted from previous publications to estimated the threshold for plasma triazolam concentrations that cause adverse events.. The pharmacokinetic/pharmacodynamic (PK/PD) model was then constructed, and the dose and administration were evaluated in various situations anticipated in medical practice. Results Among all prescriptions, 25.4% were prescribed to individuals aged 80 years or above, and 51.8% were for those aged 70 years or above. A majority of cases involved CYP3A-metabolized drug combinations, accounting for 85.6%. Elderly individuals were at a higher risk of developing delirium and fall-fracture. Based on the constructed PK/PD model, the risk of adverse events increased when the plasma concentration of triazolam exceeded the calculated threshold of 0.44 µg/mL at approximately 6 hours after administration. Administering 0.125 mg of triazolam, which is half the approved dose for the elderly in Japan, was deemed appropriate. Moreover, there was a substantial risk of adverse events even at a dosage of 0.0625 mg in combination with a moderate or strong inhibitor of cytochrome P450 3A. Conclusion Analysis by integrating large-scale databases and existing research publications on PK/PD can practically contribute to the optimization of triazolam drug therapy for the elderly in the daily clinical setting.

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Association between Elimination Half-life of Benzodiazepines and Falls in the Elderly: A Meta-analysis of Observational Studies

Cited by 7 publications

References 29 publications

Reducing the use of psychotropics in a convalescent rehabilitation ward

Reducing the use of psychotropics in a convalescent rehabilitation ward

Association between nocturnal falls and hypnotic drug use in older patients at acute care hospitals

Appropriate use of triazolam in elderly patients considering a quantitative benefit-risk assessment based on real-world data with a modeling and simulation approach

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