title: Night-to-night variability of sleep latency significantly predicts the magnitude of subsequent change in sleep latency during placebo administration.
abstract: OBJECTIVE
  To investigate the association between subjective sleep latency (sSL) fluctuation during the lead-in period and the placebo response in the subsequent double-blind period.
  
  
  METHODS
  The current study is a secondary analysis of data from the placebo arm (380 patients) of a double-blind study in outpatients with primary insomnia.
  
  
  RESULTS
  Higher fluctuation of lead-in sSL was associated with a greater decrease in sSL in the subsequent weeks. Multivariate analysis suggested that a wider standard deviation for daily sSL and a higher weekly mean sSL during the lead-in period were independent predictors of greater improvement in mean sSL during the subsequent weeks of placebo treatment. Likewise, a wider standard deviation and lower mean of subjective total sleep time (sTST) during the lead-in period were independent predictors of greater improvement in mean sTST in the subsequent weeks, but predictability of change in sTST with these parameters appears lower than those for sSL (R(2)=0.13 and 0.44, respectively, in Week 2).
  
  
  CONCLUSIONS
  The importance of night-to-night variability of sSL in sleep assessment is highlighted. Excluding patients with high variability of lead-in sSL should be considered in clinical studies evaluating an effect on sleep onset, especially in the early stages of clinical development.
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogawa
authors.forename: Shiro
authors.initials: S
authors.lastname: Hinotsu
authors.forename: Hisashi
authors.initials: H
authors.lastname: Urushihara
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000328:Adult; D000368:Aged; D002940:Circadian Rhythm / Q000502:physiology; D005260:Female; D006801:Humans; D007192:Indenes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015990:Placebo Effect; D011237:Predictive Value of Tests; D044094:Receptors, Melatonin / Q000819:agonists*; D012890:Sleep / Q000187:drug effects* / Q000502:physiology*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D007192:Indenes; D044094:Receptors, Melatonin; C495910:ramelteon