Hypnotics with novel modes of action

Hoyer, Daniel; Allen, Andrew G.; Jacobson, Laura H.

doi:10.1111/bcp.14180

Cited by 28 publications

(22 citation statements)

References 73 publications

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“…Being female had previously been reported as a risk [ 15 ], so the background of the study population could have affected the result. On use of hypnotic medications, we did not include newly available melatonin receptor agonists or orexin receptor antagonists [ 22 ], in line with our previous study [ 9 ]. However, we assumed that these drugs would not affect the risk of falls significantly, because the new drugs have a much lower incidence of side effects such as lightheadedness [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

External validation of a new predictive model for falls among inpatients using the official Japanese ADL scale, Bedriddenness ranks: a double-centered prospective cohort study

et al. 2022

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Background Several reliable predictive models for falls have been reported, but are too complicated and time-consuming to evaluate. We recently developed a new predictive model using just eight easily-available parameters including the official Japanese activities of daily living scale, Bedriddenness ranks, from the Ministry of Health, Labour and Welfare. This model has not yet been prospectively validated. This study aims to prospectively validate our new predictive model for falls among inpatients admitted to two different hospitals. Methods A double-centered prospective cohort study was performed from October 1, 2018, to September 30, 2019 in an acute care hospital and a chronic care hospital. We analyzed data from all adult inpatients, for whom all data required by the predictive model were evaluated and recorded. The eight items required by the predictive model were age, gender, emergency admission, department of admission, use of hypnotic medications, previous falls, independence of eating, and Bedriddenness ranks. The main outcome is in-hospital falls among adult inpatients, and the model was assessed by area under the curve. Results A total of 3,551 adult participants were available, who experienced 125 falls (3.5%). The median age (interquartile range) was 78 (66–87) years, 1,701 (47.9%) were men, and the incidence of falls was 2.25 per 1,000 patient-days and 2.06 per 1,000 occupied bed days. The area under the curve of the model was 0.793 (95% confidence interval: 0.761–0.825). The cutoff value was set as − 2.18, making the specificity 90% with the positive predictive value and negative predictive value at 11.4% and 97%. Conclusions This double-centered prospective cohort external validation study showed that the new predictive model had excellent validity for falls among inpatients. This reliable and easy-to-use model is therefore recommended for prediction of falls among inpatients, to improve preventive interventions. Trial registration UMIN000040103 (2020/04/08)

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Section: Discussionmentioning

confidence: 99%

External validation of a new predictive model for falls among inpatients using the official Japanese ADL scale, Bedriddenness ranks: a double-centered prospective cohort study

et al. 2022

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“…Therefore, the higher value of the disproportionality found for quetiapine cannot be understood as a greater risk of somnambulism or SRED with that drug. Indeed, as it is widely used to treat sleep disorders in North America, it is possible that the higher reporting of these events with quetiapine is due to the fact that it is prescribed to a population that has a higher prevalence of these disorders, as also are benzodiazepines and sodium oxybate 31,32 . People with insomnia may wake up at night in a confused state but not remember it, leading to a suspicion of somnambulism or SRED.…”

Section: Discussionmentioning

confidence: 99%

A safety signal of somnambulism with the use of antipsychotics and lithium: A pharmacovigilance disproportionality analysis

Gouverneur

Ferreira

Morival

et al. 2021

Brit J Clinical Pharma

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Aims Antipsychotics and lithium are widely used in psychiatry, particularly in schizophrenia and bipolar disorders. Recently, some cases of somnambulism or sleep‐related eating disorder (SRED) have been reported in patients treated with these drugs. This study investigated the risk of reporting somnambulism or SRED associated with the use of antipsychotics and lithium. Methods The World Health Organization pharmacovigilance database (VigiBase), comprising >18 million adverse events, was queried. All somnambulism or SRED reports related to antipsychotics or lithium were identified. The association between antipsychotics or lithium and somnambulism or SRED was computed using the proportional reporting ratio (PRR) and information component. Results Among the 5784 cases reporting somnambulism or SRED, 508 suspected at least 1 antipsychotic or lithium. Most patients were aged 18–64 years (62.0%), and 37.0% were men. In most cases (77.6%), antipsychotic or lithium were the only drug class involved, and 53.3% of cases suspected quetiapine. Somnambulism was reported in 88.6% of cases and SRED in 18.1%. A significant association was found for second‐generation antipsychotics (PRR 3.44, 95% confidence interval 3.13) and lithium (PRR 2.03, [1.22; 3.37]), but not for first‐generation antipsychotics (PRR 0.99, [0.68; 1.44]). Conclusions We found a significant signal of somnambulism or SRED related to second‐generation antipsychotics and lithium. While case reports mentioned mostly quetiapine and olanzapine, almost all second‐generation antipsychotics were associated with somnambulism or SRED.

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“…Significant efforts have been made in recent years to produce novel small molecule orexin agonists and antagonists which hold exciting potential for future therapeutics. The translation of these compounds to clinical use has been recently demonstrated with Lemborexant being approved in the US and Japan, and the FDA approving daridorexant in January 2022, as well as other compounds, e.g., seltorexant, being in late stage clinical development ( Dauvilliers et al, 2020 ; Hoyer et al, 2020 ; Kaufmann et al, 2020 ; Muehlan et al, 2020a , b ; Zammit et al, 2020a , b ).…”

Section: Ligandsmentioning

confidence: 99%

Orexin Signaling: A Complex, Multifaceted Process

Dale

Hoyer²,

Jacobson³

et al. 2022

Front. Cell. Neurosci.

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The orexin system comprises two G protein-coupled receptors, OX1 and OX2 receptors (OX1R and OX2R, respectively), along with two endogenous agonists cleaved from a common precursor (prepro-orexin), orexin-A (OX-A) and orexin-B (OX-B). For the receptors, a complex array of signaling behaviors has been reported. In particular, it becomes obvious that orexin receptor coupling is very diverse and can be tissue-, cell- and context-dependent. Here, the early signal transduction interactions of the orexin receptors will be discussed in depth, with particular emphasis on the direct G protein interactions of each receptor. In doing so, it is evident that ligands, additional receptor-protein interactions and cellular environment all play important roles in the G protein coupling profiles of the orexin receptors. This has potential implications for our understanding of the orexin system’s function in vivo in both central and peripheral environments, as well as the development of novel agonists, antagonists and possibly allosteric modulators targeting the orexin system.

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Hypnotics with novel modes of action

Cited by 28 publications

References 73 publications

External validation of a new predictive model for falls among inpatients using the official Japanese ADL scale, Bedriddenness ranks: a double-centered prospective cohort study

External validation of a new predictive model for falls among inpatients using the official Japanese ADL scale, Bedriddenness ranks: a double-centered prospective cohort study

A safety signal of somnambulism with the use of antipsychotics and lithium: A pharmacovigilance disproportionality analysis

Orexin Signaling: A Complex, Multifaceted Process

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