Sleep and residual sedation after administration of zaleplon, zolpidem, and placebo during experimental middle-of-the-night awakening.
OBJECTIVE
To assess the efficacy of zaleplon 10 mg and zolpidem 10 mg administered during experimental middle-of-the-night awakenings in patients with sleep-maintenance insomnia using objective polysomnographic measures and to assess daytime residual sedation 4 to 7 hours after dosing using sleep-latency testing.


METHODS
A randomized, double-blind, placebo-controlled, 3-period, crossover design was used to study 37 adults with insomnia who received treatment during an experimental awakening 4 hours after bedtime. Latency to persistent sleep and total sleep time before and after awakening were recorded. The primary residual sedation measure was a sleep latency test conducted hourly from 4 to 7 hours after treatment. Self-report measure of alertness and concentration and digit symbol substitution tests were examined concurrently.


METHODS
Sleep disorders centers.


METHODS
Thirty-seven adults with sleep-maintenance insomnia.


METHODS
Zaleplon 10 mg, zolpidem 10 mg, or placebo.


RESULTS
Thirty-one patients had efficacy-evaluable data; 37 patients received at least 1 dose of study medication and were included in the safety analysis. Compared with placebo, latency to persistent sleep after both zaleplon and zolpidem was shorter and total sleep time after administration of the drugs was longer (overall p < .001, Dunnett p < .001 for all posthoc comparisons). Significant differences from placebo were not found with zaleplon in daytime-sedation measures. At 4, 5, and 7 hours after zolpidem, sleep onset on sleep latency testing was shorter than after placebo (overall p < .001 for all, Dunnett tests for posthoc comparisons p < .001, p < .001, p < .05, respectively). Self-report measures of concentration (4, 5, and 6 hours, overall p < .05, Dunnett p < .05 for each time point) and alertness (4 hours, overall p < .05, Dunnett p < .05), and Digit Symbol Substitution Test scores (4 and 5 hours, overall p < .001, Dunnett p < .01 for both time points) after zolpidem were also lower than with placebo.


CONCLUSIONS
Zaleplon 10 mg and zolpidem 10 mg effectively shorten sleep latency and lengthen sleep duration after dosing, when administered during experimental nocturnal awakening. Residual sedation was not detected as little as 4 hours after zaleplon 10 mg, whereas residual sedation was detected with zolpidem 10 mg up to 7 hours after treatment. These findings suggest that zaleplon may be an appropriate treatment for use when patients awaken during the night and have difficulty reinitiating sleep.
Zammit
Gary K
GK
Clinilabs Sleep Disorders Institute, St. Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY 10019, USA. gzammit@clinilabs.com
Corser
Bruce
B
Doghramji
Karl
K
Fry
June M
JM
James
Steven
S
Krystal
Andrew
A
Mangano
Richard M
RM
D000081:Acetamides / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017286:Polysomnography; D011725:Pyridines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D020178:Sleep Disorders, Circadian Rhythm / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome; D014851:Wakefulness; D000077334:Zolpidem
D000081:Acetamides; D006993:Hypnotics and Sedatives; D011725:Pyridines; D011743:Pyrimidines; D000077334:Zolpidem; C085665:zaleplon