EEG Power Spectra Response to a 4-h Phase Advance and Gaboxadol Treatment in 822 Men and Women

Abstract

To explore the effect of gaboxadol on NREM EEG in transient insomnia using power spectral analysis and evaluate the response between men and women. This was a randomized, double-blind, 3-way, parallel-group transient insomnia study in 22 sleep laboratories. After a baseline night (N1), subjects underwent a 4-h phase-advance of their habitual sleep time the following night (N2). Healthy subjects aged 18-64 y were given single-blind placebo on N1 followed by double-blind treatment on N2 (gaboxadol 10 mg [n = 271], 15 mg [n = 274], or placebo [n = 277]) At baseline, women showed significantly greater values in low frequency activity (< 10 Hz) and in high spindle/low beta frequency activity (14-18 Hz) compared to men. During the phase advance (placebo N2-baseline N1), there was a significant increase in power within the high spindle/low beta frequency range (15-17 Hz) and a significant reduction in beta activity (20-32 Hz), which was greater in women than men. Gaboxadol induced a significant (dose-related) increase in low frequencies (< 8 Hz) and a significant (dose-related) decrease within the alpha/spindle range (11-12 Hz). The effect was dependent upon sex, with a greater magnitude of effect observed in women than men. Gaboxadol shows a characteristic NREM EEG spectral profile in a model of transient insomnia. Men and women show clear differences in NREM EEG activity at baseline, to gaboxadol treatment and to phase-shifts in habitual sleep/wake times. The exact mechanisms underlying the sex differences remain unclear, but sex is an important variable in studies evaluating sleep and gaboxadol. TRIAL REGISTRY INFORMATION: www.clinicaltrials.gov, study identifier: NCT00102167.