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Efficacy of SM‐1 in a transient insomnia model
Author(s) -
Dahl Thomas,
Chen Lan Bo,
Zammit Gary,
Ahmad Maha,
Roth Thomas
Publication year - 2019
Publication title -
human psychopharmacology: clinical and experimental
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.461
H-Index - 78
eISSN - 1099-1077
pISSN - 0885-6222
DOI - 10.1002/hup.2713
Subject(s) - sleep onset , somnolence , placebo , polysomnography , primary insomnia , diphenhydramine , insomnia , anesthesia , medicine , psychology , clinical endpoint , adverse effect , sleep disorder , randomized controlled trial , psychiatry , apnea , alternative medicine , pathology , histamine
Objectives The objectives of this study were primarily to assess the efficacy and safety of SM‐1 in a circadian challenge model of transient insomnia and secondarily, to assess the contribution of diphenhydramine to the combination. Methods Randomized, double‐blind, placebo‐controlled three‐way cross‐over study with a 5‐hr phase advance. Subjects were 39 healthy adults reporting a history of transient insomnia. All treatments (SM‐1, SM‐1 without diphenhydramine, or placebo) were administered to all subjects in a randomly assigned sequence, with at least 1 week between treatments. The primary endpoint was total sleep time (TST) determined by polysomnography. Secondary endpoints included wakefulness after sleep onset (WASO), latency to persistent sleep, number of awakenings (NAW), subjective TST (sTST) and sleep latency (sSL), TST, and NAW by quarters of the night and sleep quality. Safety endpoints included adverse events, Karolinska Sleepiness Scale digit symbol substitution test, and subject‐reported alertness level. Results SM‐1 provided an increase of 126.7 min in TST over placebo ( p < .001). WASO, sTST, sleep quality, and sSL also showed significant improvement. Diphenhydramine demonstrated a significant ( p = .014) contribution of 43.7 min to TST. SM‐1 was well‐tolerated with type and frequency of adverse events comparable with placebo, and no residual sleepiness upon awakening after 8 hr. Conclusions SM‐1 provided a robust and statistically significant increase in TST compared with placebo in a circadian model of transient insomnia, without evidence of next‐day impairment. Diphenhydramine contributed to the effect.