Noise-induced sleep maintenance insomnia: hypnotic and residual effects of zaleplon.
OBJECTIVE
The primary objective of the study was to assess the residual effects of zaleplon in the morning, 4 h after a middle-of-the-night administration. The secondary objective was to investigate the effectiveness of zaleplon in promoting sleep in healthy volunteers with noise-induced sleep maintenance insomnia.


METHODS
Thirteen healthy male and female volunteers (aged 20-30 years) with normal hearing, who were sensitive to the sleep-disrupting effects of noise, participated in a double-blind, placebo- and active-drug controlled, four-period cross-over study. The subjects were permitted to sleep for 5 h (22.45-03.45 h) in a quiet environment before they were awoken. At 04.00 h they ingested 10 mg zaleplon, 20 mg zaleplon, 7.5 mg zopiclone (active control), or placebo before a second period of sleep (04.00-08.00 h), during which they were exposed to an 80 dB(A) 1 kHz pure tone pulse with an inter-tone interval of 1 s and a duration of 50 ms. The sound stimulus was stopped after 10 min of persistent sleep or after 2 h if the subject had not fallen asleep. Residual effects were assessed at 08.00 h (4 h after drug administration) using the digit symbol substitution test (DSST), choice reaction time (CRT), critical flicker fusion (CFF), and immediate and delayed free recall of a 20 word list. The data were analysed by analysis of variance. A Bonferroni adjustment was made for the three active treatments compared with placebo.


RESULTS
There were no residual effects of zaleplon (10 and 20 mg) compared with placebo. Zopiclone impaired memory by delaying the free recall of words (P = 0.001) and attenuated performance on DSST (P = 0.004) and CRT (P = 0.001), compared with placebo. Zaleplon reduced the latency to persistent sleep (10 mg, P = 0.001; 20 mg, P = 0.014) and the 20 mg dose reduced stage 1 sleep (P = 0.012) compared with placebo. Zopiclone reduced stage 1 sleep (P = 0.001), increased stage 3 sleep (P = 0.0001) and increased total sleep time (P = 0.003), compared with placebo.


CONCLUSIONS
Zaleplon (10 mg and 20 mg), administered in the middle of the night 4 h before arising, shortens sleep onset without impairing next-day performance.
Stone
Barbara M
BM
QinetiQ Ltd, Centre for Human Sciences, Farnborough, Hampshire, GU14 0LX, UK. bmstone@QinetiQ.com
Turner
Claire
C
Mills
Sue L
SL
Paty
Isabelle
I
Patat
Alain
A
Darwish
Mona
M
Danjou
Philippe
P
D000081:Acetamides / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D018849:Controlled Clinical Trials as Topic; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004569:Electroencephalography; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D009622:Noise / Q000009:adverse effects*; D011597:Psychomotor Performance / Q000187:drug effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000503:physiopathology
D000081:Acetamides; D006993:Hypnotics and Sedatives; D011743:Pyrimidines; C085665:zaleplon