Can an inert sleeping pill affect sleep? Effects on polysomnographic, behavioral and subjective measures

Rationale: Since two recent meta-analyses on sleep changes associated with placebo in clinical trials suggested a beneficial effect of placebo treatments, pointing to a dissociation between subjective and objective measures of sleep, the current experiment was directly aimed to assess the effects of an inert compound, administered with the suggestion that it was a hypnotic substance in subjects with mild sleep complaints. Objectives: The aim of this study was to compare subjective, behavioral, polysomnographic (PSG), and quantitative electroencephalographic (EEG) changes during a night preceded or not by the intake of two 50-mg lactose capsules. Methods: Ten female students, selected by the Pittsburgh Sleep Quality Index, slept for three consecutive nights in a sleep laboratory, with the experimental (EXP) night defined by the administration of two 50-mg lactose pills. Self-ratings of sleep quality and performance were assessed upon morning awakening of baseline (BSL) and EXP nights. Results: The EXP nights were self-rated as more restful and characterized by a decreased number of nocturnal awakenings than the BSL nights. PSG measures showed that wakefulness after sleep onset significantly decreased during the EXP night as compared to the BSL night. The EXP nights also showed an increase of 0.5-4.0 Hz power during nonrapid eye movement sleep and a decrease of EEG activity in the beta frequency range during rapid eye movement sleep only at central brain sites. A specific improvement of behavioral measures was also found upon morning awakening after the EXP night compared to the BSL night. Conclusions: The administration of an inert pill improves both the subjective and objective quality of sleep. The reduced sleep fragmentation and the effects on some quantitative EEG markers of sleep homeostasis suggest that the experimental manipulation induced coherent changes in the subsequent sleep, resembling an enhancement of sleep pressure. The regional differences of EEG activity suggest the involvement of a specific physiological mechanism distinct from that of effective treatments.