Night-to-night variability of sleep latency significantly predicts the magnitude of subsequent change in sleep latency during placebo administration

ObjectiveTo investigate the association between subjective sleep latency (sSL) fluctuation during the lead-in period and the placebo response in the subsequent double-blind period.MethodsThe current study is a secondary analysis of data from the placebo arm (380 patients) of a double-blind study in outpatients with primary insomnia.ResultsHigher 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 (R2 = 0.13 and 0.44, respectively, in Week 2).ConclusionsThe 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.