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.
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