ABSTRACT
Slow wave sleep (SWS) has been reported to correlate with sleep maintenance, but whether pharmacological enhancement of SWS also leads to improved sleep maintenance is not known. Here we evaluate the time-course of the effects of gaboxadol, an extra-synaptic gamma-aminobutyric acid (GABA) agonist, on SWS, sleep maintenance, and other sleep measures in a traffic noise model of transient insomnia. After a placebo run-in, 101 healthy subjects (20-78 y) were randomized to gaboxadol (n = 50; 15 mg in subjects <65 y and 10 mg in subjects ≥65 y) or placebo (n = 51) for 7 nights (N1-N7). The model caused some disruption of sleep initiation and maintenance, with greatest effects on N1. Compared with placebo, gaboxadol increased SWS and slow wave activity throughout N1 to N7 (p < 0.05). Gaboxadol reduced latency to persistent sleep overall (N1-N7) by 4.5 min and on N1 by 11 min (both p < 0.05). Gaboxadol increased total sleep time (TST) overall by 16 min (p < 0.001) and on N1 by 38 min (p < 0.0001). Under gaboxadol, wakefulness after sleep onset was reduced by 11 min overall (p < 0.01) and by 29 min on N1 (p < 0.0001), and poly-somnographic awakenings were reduced on N1 (p < 0.05). Gaboxadol reduced self-reported sleep onset latency overall and on N1 (both p < 0.05) and increased self-reported TST overall (p < 0.05) and on N1 (p < 0.01). Subjective sleep quality improved overall (p < 0.01) and on N1 (p < 0.0001). Increases in SWS correlated with objective and subjective measures of sleep maintenance and subjective sleep quality under placebo and gaboxadol (p < 0.05). Gaboxadol enhanced SWS and reduced the disruptive effects of noise on sleep initiation and maintenance.
