Usefulness of Temazepam and Zaleplon to Induce Afternoon Sleep

Military Medicine, Oct 2006 by Simons, Ries

Insufficient daytime sleep may result in reduction of effectiveness and safety during overnight military missions. The usefulness of temazepam and zaleplon to optimize afternoon sleep and their effects on performance and alertness during a subsequent night shift were studied. Method: In a randomized double-blind within-subjects design, 11 subjects took 20 mg of temazepam, 10 mg of zaleplon, or placebo before a 5:30-10:00 p.m. sleep period. Sleep length and quality were measured. Subjects were kept awake throughout the night while alertness, cognitive performance, and muscle power were repeatedly measured. Results: Temazepam provided significantly longer and qualitatively better sleep than zaleplon or placebo. During the night, sleepiness increased and muscle power was impaired in all conditions. Better sleep was correlated with less sleepiness during the night. Conclusion: Temazepam is useful to optimize a 4.5-hour afternoon sleep before overnight missions. Irrespective of hypnotic treatment, sleepiness and fatigue increased during the night shift.

Introduction

Military round-the-clock operations are characterized by circadian disruption, rapid work shift changes, prolonged duty, nonoptimal sleep facilities, sleep loss, and high stress levels. These factors may result in high levels of fatigue and sleepiness when on duty, with consequent reduction of operational effectiveness and safety.1 Sleep deprivation is an important cause of impaired performance of crew.2-5 Rapid changes from day-to-night shift may require crew to sleep before their duty.6 Because in the afternoon the body clock dictates wakefulness, it is anticipated that efficiency and quality of sleep in the afternoon will be low.7 Poor preduty sleep may lead to impaired alertness and performance during a night shift.5 To optimize daytime sleep, hypnotics may be required and 10-20 mg of temazepam has been recommended for aircrew, in cases where preservation of sleep is crucial.8,9 The recently developed nonbenzodiazepine zaleplon may also be considered for optimizing sleep in military crew. It has an elimination half-life of approximately 1 hour and appears to facilitate falling asleep but the effect on total sleep time (TST) is unclear.10 Zaleplon had no negative effects on performance following a 3.5-hour daytime sleep.11

This study was conducted to assess the usefulness of temazepam (20 mg) and zaleplon (10 mg) to improve 4.5 hours of sleep in the afternoon to optimize performance and alertness during subsequent night shift work.

Methods

Subjects

Twelve healthy male volunteers (mean age, 23.0 years; range, 19-35 years), participated in the study. Subjects had no history of insomnia, were nonsmokers, and were drug free from 3 months before the study. The medical ethical committee of the Central Military Hospital of The Netherlands granted approval of the study. Informed consent was obtained from all subjects after a full explanation of the nature of the study. Subjects were paid for their participation.

Assessment Methods

Quality of sleep on the trial day was assessed by a version of the Groningen Sleep Quality Scale (AGSQS) that was adjusted for a sleep period shorter than 5 hours12. The result of the AGSQS is a quality score ranging from 0 (very good) to 13 (very poor). Subjects also estimated their TST. An actigraph device (Actiwatch Plus, Cambridge Neurotechnology, Cambridge, United Kingdom) was used to record objective TST, sleep efficiency (TST/time in bed x 100%), and fragmentation index during the sleep period after drug intake.13,14 The Stanford Sleepiness Scale (SSS; Ref. 15) was used to assess subjective sleepiness at baseline and during the night shift. The result of the SSS is a score with increasing sleepiness from 1 to 7.

Each cognitive performance test session included a vigilance and tracking task (VigTrack) and the Multi-Attribute Task battery (MAT). The VigTrack task16,17 is a dual task performed on a handheld computer measuring vigilance performance under the continuous load of a compensatory tracking task. The MAT battery18,19 includes a system monitoring task, tracking task, communication task, and a resource management task, which has to be performed simultaneously. This complex informationprocessing task is performed on a personal computer.

Maximal isometric muscle power of the underarm20 was measured during each test session. Subjects had to squeeze two vertically fixed grips with the preferred hand and exert full strength for 3 seconds. The best period of 2 seconds of the maximal force (N) delivery was taken as result.

Design and Treatments

Using the double-dummy technique, single doses of 20 mg of temazepam (rapidly absorbed formulation), 10 mg of zaleplon, and placebo were randomly used in a double-blind crossover design (sequentially balanced Latin square). Between the drug administrations, there was a wash-out period of 7 days.

Procedure

Volunteers were medically examined and trained on the performance tests. The night before each trial day, subjects slept at home from 11:00 p.m. until 7:00 a.m. Each test session included the SSS, VigTrack (10 minutes), MAT battery (10 minutes), and isometric power testing of the underarm. On trial days, subjects performed a baseline test session before the sleep period and rated the subjective characteristics of their sleep at home (quality, TST, bedtime, wake-up time). After the baseline session, they were in bed in a darkened room from 5:30 p.m. until 10:00 p.m., wearing the Actiwatch device on their nondominant wrist. After waking up at 10:00 p.m., subjects rated their sleep (quality, TST, latency, number of awakenings). After 10:00 p.m., subjects were kept awake and another six test sessions were performed at regular intervals from 10:15 p.m. until 7:00 a.m.