The Effects of Benzodiazepine and Nonbenzodiazepine Agents, Ramelteon, Low-dose Doxepin, Suvorexant, and Selective Serotonin 5-HT_2A Receptor Antagonists and Inverse Agonists on Sleep and Wakefulness

Abstract

1 provides a classification system of sleep stages that comprises the following three different states: wakefulness (W), nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Relaxed W is characterized by an electroencephalogram (EEG) with alpha activity (8-12 Hz) intermixed with lower amplitude irregular beta waves (13-35 Hz), slow or rapid electrooculogram, eyelid blinks, a relatively high tonic electromyogram (EMG), and movement artifacts. NREM sleep is characterized by the following: stage N1 sleep represents the transition from W to sleep and is characterized by the presence of relatively low-voltage, mixed frequency waves (4-7 Hz range) with a prominence of activity in the theta range. It is viewed as a shallow sleep during which the subject can be easily aroused. Stage N2 sleep is the first unequivocal stage of sleep, which is characterized by the presence of two types of EEG signals, namely the sleep spindles (12-14 Hz) and the K-complexes. During this stage, a more intense stimulus is needed to arouse the subject. Stage N3 sleep is characterized by the occurrence of slow high-amplitude delta waves (frequency of ∼0.5-2 Hz). It is also known as slow wave sleep (SWS) or delta sleep. REM sleep is characterized by the presence of low-voltage mixed frequency EEG activity, which closely resembles that of stage N1 sleep. Often observed against this background are sawtooth waves (theta activity, 4-7 Hz) in conjunction with bursts of REMs. In contrast, muscles are completely relaxed (with the exception of the extraocular muscles and the diaphragm). However, the flat EMG tracing can be periodically interrupted by muscle twitches. Of note is the fact that typically the first half of the night is dominated by stage N3 sleep, whereas REM sleep predominates in the second half of the night.Age and gender variables have been shown to have associations with the duration of sleep stages. Young adults spend

Preventive Effects of Ramelteon, Suvorexant, and Lemborexant on Delirium in Hospitalized Patients With Physical Disease

“…Olanzapine has been reported to be associated with delirium prevention, 22 and multiple studies have indicated that olanzapine increases slow wave sleep and REM sleep. 55,56,66,67 A previous study reported that ramelteon had no effect on REM sleep (Table 5), 57 and in the present study, ramelteon did not show delirium-prevention effects. Consistent with this result, meta-analyses 40,41 and an RCT 42 have shown that ramelteon does not prevent delirium.…”

“…13 Table 5 summarizes the sleep architecture during delirium and the effect of each sleepinducing medication on sleep. 17,[57][58][59] During delirium, rapid eye movement (REM) sleep and total sleep time (TST) are reduced 17,59 ; in particular, patients with serious disease have frequent awakenings and decreased REM sleep. 59 The reduction in REM sleep is attributed to increased inflammatory cytokine levels owing to DSWR.…”

“…Previous reports 23,69,70 have suggested that the use of benzodiazepines is more likely to induce delirium than nonuse, and the present study showed similar results. This is likely because benzodiazepines decrease both non-REM and REM sleep (Table 5), 57 causing a state similar to sleep resulting in delirium. In addition, Z-drugs did not affect REM sleep (Table 5), 57 and the present study also showed that Z-drugs (zolpidem, zopiclone, and eszopiclone) did not affect the development of delirium.…”

“…This is likely because benzodiazepines decrease both non-REM and REM sleep (Table 5), 57 causing a state similar to sleep resulting in delirium. In addition, Z-drugs did not affect REM sleep (Table 5), 57 and the present study also showed that Z-drugs (zolpidem, zopiclone, and eszopiclone) did not affect the development of delirium. Previous reports [71][72][73][74] have shown that zolpidem reduces REM sleep and can induce delirium.…”

Insomnia among Cancer Patients in the Real World: Optimising Treatments and Tailored Therapies

“…However, in advanced stages of the disease, concern about dependence should not prevent their prescription. Benzodiazepine can also alter the sleep architecture, increasing the N2 stage and decreasing the N3 and REM stages of sleep [67]. The Zolpidem augmentation of treatment with Venlafaxine and SSRI has shown to improve sleep and quality of life in breast cancer survivors [68].…”