Zaleplon and Zolpidem Objectively Alleviate Sleep Disturbances in Mountaineers at a 3,613 Meter Altitude

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Abstract
To assess the effects of zolpidem and zaleplon on nocturnal sleep and breathing patterns at altitude, as well as on daytime attention, fatigue, and sleepiness. Double-blind, randomized, placebo-controlled, cross-over trial. 3 day and night alpine expedition at 3,613 m altitude. 12 healthy male trekkers. One week spent at 1,000 m altitude (baseline control), followed by 3 periods of 3 consecutive treatment nights (N1–3) at altitude, to test 10 mg zolpidem, 10 mg zaleplon, and placebo given at 21:45. Sleep from EEG, actigraphy and sleep logs; overnight arterial saturation in oxygen (SpO2) from infrared oximetry; daytime attention, fatigue and sleepiness from a Digit Symbol Substitution Test, questionnaires, and sleep logs; acute mountain sickness (AMS) from the Lake Louise questionnaire. Compared to baseline control, sleep at altitude was significantly impaired in placebo subjects as shown by an increase in the amount of Wakefulness After Sleep Onset (WASO) from 17 ± 8 to 36 ± 13 min (P<0.05) and in arousals from 5 ± 3 to 20 ± 8 (P<0.01). Slow wave sleep (SWS) and stage 4 respectively decreased from 26.7% ± 5.8% to 20.6% ± 5.8% of total sleep time (TST) and from 18.2% ± 5.2% to 12.4% ± 3.1% TST (P<0.05 and P<0.001, respectively). Subjects also complained from a feeling of poor sleep quality combined with numerous O2 desaturation episodes. Subjective fatigue and AMS score were increased. Compared to placebo control, WASO decreased by ~6 min (P<0.05) and the sleep efficiency index increased by 2% (P<0.01) under zaleplon and zolpidem, while SWS and stage 4 respectively increased to 22.5% ± 5.4% TST (P<0.05) and to 15.0% ± 3.4% TST (P<0.0001) with zolpidem only; both drugs further improved sleep quality. No adverse effect on nighttime SpO2, daytime attention level, alertness, or mood was observed under either hypnotic. AMS was also found to be reduced under both medications. Both zolpidem and zaleplon have positive effects on sleep at altitude without adversely affecting respiration, attention, alertness, or mood. Hence, they may be safely used by climbers.

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