GABA receptor agonists(Massachusetts General Hospital Clinical Research Program)

One of the most serious neurological disorders is epilepsy. This study aimed to investigate the effects of baclofen, a GABA receptor agonist, on pain and seizure thresholds, as well as on oxidative damage in brain mitochondrial membranes of mice. Sixty male mice were divided into 10 groups. Control, baclofen (1, 5, and 10 mg/kg) with short-term exposure (1 day), long-term exposure (7 days), and withdrawal syndrome (eight days). The withdrawal syndrome was evaluated one day after the last dose of the drug. Hotplate and tail-flick tests were performed to assess pain threshold, and the rotarod was used to assess motor coordination. The seizure threshold and oxidative stress markers, including reactive oxygen species (ROS), malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH), and the MTT assay, were investigated. The results showed that baclofen (10 mg/kg) in short-term and all doses (1, 5, and 10 mg/kg) in long-term increased the seizure threshold. Evaluation of motor function and coordination in mice revealed decreased motor activity. The effect of baclofen on oxidative damage showed that, in long-term exposure, it improved mitochondrial ROS, malondialdehyde, and GSH levels. Protein carbonyl and MTT tests did not show a significant difference. A GABAB receptor agonist causes a dose- and time-dependent increase in the seizure threshold. Baclofen could reduce oxidative damage by decreasing ROS levels and malondialdehyde formation, and increasing GSH content.

To investigate sleep medication prescriptions over a 3‐year period for all patients including those with dementia who admitted to Kyushu University Hospital, as well as trends in incident reports, such as fall and delirium, in the hospital over the same period.

This study included 15,721 patients (22,229 prescriptions) who were hospitalized at Kyushu University Hospital (Fukuoka, Japan) between April 1, 2019, and March 31, 2021, and were prescribed sleep medication during their hospital stay. Data on prescribed sleep medications, dementia status, and psychiatric liaison interventions were extracted from medical records. Additionally, information on falls, delirium, and self‐removal of drains and tubes was collected from in‐hospital incident reports. The study was approved by the Ethics Committee of the Faculty of Medical Sciences, Kyushu University.

Among all hospitalized patients, the proportion of GABA receptor agonist prescriptions decreased from 54% in 2019 to 37% in 2021, while the proportion of orexin receptor antagonist prescriptions increased from 34% to 52% over the same period. Similar trends were observed in a subgroup analysis of patients who received psychiatric liaison team interventions, including those with dementia, where the proportion of orexin receptor antagonist prescriptions increased from 48% to 65%. During this period, the number of in‐hospital incidents, such as delirium, falls, and self‐removal of drains and tubes, showed a decreasing trend that inversely correlated with the increased prescription of orexin receptor antagonists. Notably, the number of incidents involving delirium was reduced by approximately half.

This study demonstrated that a shift in sleep medication prescriptions from GABA receptor agonists to orexin receptor antagonists were observed among 15,721 hospitalized patients, even in general medical departments. The observed decreasing trend in the number of incidents, such as falls and delirium in patients with dementia, suggests that changes in hypnotic prescription patterns may have contributed to these improvements.