Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people

Abstract

Current pharmacological treatments for insomnia include benzodiazepine and non-benzodiazepine hypnotics targeting γ-aminobutyric acid (GABA) A receptors, as well as agonists of the melatonin receptors MT1 and MT2. Melatonin, temazepam and zolpidem are thought to exert their effect through different mechanisms of action, but whether this leads to differential effects on electroencephalogram (EEG) power spectra during sleep in middleaged people is currently not known. To establish whether the effects of prolonged-release melatonin (2 mg) on the nocturnal sleep EEG are different to those of temazepam (20 mg) and zolpidem (10 mg). Sixteen healthy men and women aged 55-64 years participated in a double-blind, placebocontrolled, four-way cross-over trial. Nocturnal sleep was assessed with polysomnography and spectral analysis of the EEG. The effects of single oral doses of prolonged-release melatonin, temazepam and zolpidem on EEG slow-wave activity (SWA, 0.75-4.5 Hz) and other frequencies during nocturnal non-rapid eye movement (NREM) sleep were compared. In an entire night analysis prolonged-release melatonin did not affect SWA, whereas temazepam and zolpidem significantly reduced SWA compared with placebo. Temazepam significantly reduced SWA compared with prolonged-release melatonin. Prolonged-release melatonin only reduced SWA during the first third of the night compared with placebo. These data show that the effects of prolonged-release melatonin on the nocturnal sleep EEG are minor and are different from those of temazepam and zolpidem; this is likely due to the different mechanisms of action of the medications.

Efficacy of a Topical Aromatic Rub (Vicks VapoRub<sup>®</sup>) on Effects on Self-Reported and Actigraphically Assessed Aspects of Sleep in Common Cold Patients

“…To place this change in perspective it is noted that the observed response to VVR compared to placebo for the SQSQ was 7.9 units, which is comparable to the positive effects of gaboxadol on subjective sleep quality in a traffic noise model of sleep disruption [20] and approximately half the size of the effect of zolpidem and temazapam on sleep in middle-aged people [25]. Supporting this is the finding that responses to the "How refreshed did you feel upon waking?"…”

“…question of the SQSQ, a validated questionnaire which has been shown to be sensitive to effects of zolpidem, temazepam [25], gaboxadol and traffic noise [20] and slow wave sleep disruption by acoustic stimuli [26], was chosen as the primary endpoint. The KSD questionnaire [21], [27] was modified for this study by removing the first 5 questions due to duplication of sleep measures with the SQSQ.…”

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

“…Unlike current hypnotics of the benzodiazepine and non‐benzodiazepine (Z‐drugs) class, melatonin preserves physiological sleep structure and architecture and does not suppress SWS (Zisapel, 2012; Arbon et al, 2015). Through its activity on sleep and the circadian clock, add‐on PRM to anti‐hypertensive therapy can potentially improve clinical outcome in hypertensive patients with insomnia.…”

“…However, activation of this brain area is decreased concomitantly with the endogenous rise of melatonin, so that administration of exogenous melatonin at night does not have a further notable effect (Figure 1B,C). Because melatonin does not increase the amount of SWS (Arbon et al, 2015), which is considered a marker of the homeostatic sleep pressure (Zisapel, 2007), the sleep promoting effects of melatonin may be mostly ascribed to the circadian component of sleep regulation.…”

A systematic review of treatments for sleepwalking: 100 years of case studies

“…Benzodiazepines, for example, potentiate the inhibitory effects of GABA throughout the CNS, resulting in anxiolytic, sedative, hypnotic, muscle relaxant and antiepileptic effects (Rossi, 2015) and reduce slow wave sleep (Arbon, Knurowska, & Dijk, 2015;Plante et al, 2016;Shrivastava, Jung, Saadat, Sirohi, & Crewson, 2014;Stockmann et al, 2015). Antidepressants are also thought to reduce sleepwalking either through their antianxiolytic properties (Liliwhite, Wilson, & Nutt 1994) or by reducing partial arousal, characteristic of sleepwalking (Frölich, Wiater, & Lehmkuhl, 2001).…”