Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis.

Previous studies have reported inconsistent results about exogenous melatonin's sleep-promoting effects. A possible explanation relies on the heterogeneity in administration schedule and dose, which might be accountable for differences in treatment efficacy. In this paper, we undertook a systematic review and meta-analysis of double-blind, randomized controlled trials performed on patients with insomnia and healthy volunteers, evaluating the effect of melatonin administration on sleep-related parameters. The standardized mean difference between treatment and placebo groups in terms of sleep onset latency and total sleep time were used as outcomes. Dose-response and meta-regression models were estimated to explore how time of administration, dose, and other treatment-related parameters might affect exogenous melatonin's efficacy. We included 26 randomized controlled trials published between 1987 and 2020, for a total of 1689 observations. Dose-response meta-analysis showed that melatonin gradually reduces sleep onset latency and increases total sleep time, peaking at 4 mg/day. Meta-regression models showed that insomnia status (ß = 0.50, p < 0.001) and time between treatment administration and the sleep episode (ß = -0.16, p = 0.023) were significant predictors of sleep onset latency, while the time of day (ß = -0.086, p < 0.01) was the only significant predictor of total sleep time. Our results suggest that advancing the timing of administration (3 h before the desired bedtime) and increasing the administered dose (4 mg/day), as compared to the exogenous melatonin schedule most used in clinical practice (2 mg 30 min before the desired bedtime), might optimize the efficacy of exogenous melatonin in promoting sleep.

The fear of spiders: perceptual features assessed in augmented reality.

Background: Persons with specific phobias typically generalize the dangerousness of the phobic animal to all members of its species, possibly as a result of malfunctioning brain circuitry normally providing quick and dirty identification of evolutionary-relevant stimuli. An objective assessment of which perceptual features make an animal more or less scary to phobic and non-phobic people would help overcome the limitations of the few studies available so far, based on self-reports. Objective: To achieve this aim, we built an augmented reality setting where volunteers with different levels of fear of spiders were asked to make holographic spiders that look either dangerous or harmless. To reach this goal, a computerized interface allowed participants to modify the spider's perceptual features (hairiness, body/leg size, and locomotion) in real time. Results: On average, the dangerous spiders were made hairy, thick, and moving according to spider-like locomotion; coherently, the harmless spiders were made hairless, slim, and moving according to a butterfly-like locomotion. However, these averaged preferences could not fully describe the complex relationship between perceptual preferences with each other and with arachnophobia symptoms. An example of a key finding revealed by cluster analysis is the similarity in perceptual preferences among participants with little or no fear of spiders, whereas participants with more arachnophobia symptoms expressed more varying preferences. Conclusion: Perceptual preferences toward the spider's features were behaviorally assessed through an observational study, objectively confirming a generalization effect characterizing spider-fearful participants. These results advance our knowledge of phobic preferences and could be used to improve the acceptability of exposure therapies.