Journal Article

Effects of zolpidem and zaleplon on cognitive performance after emergent morning awakenings at Tmax: a randomized placebo-controlled trial

Johnston, Smith L, Baskin, Pamela, Basner, Mathias, Dinges, David F, Ecker, Adrian J

2019

Overview

Abstract Study Objectives Prescription sleep aids are frequently used in the general population and even more frequently in spaceflight. To evaluate the risk to operational safety, a ground-based, double-blind, placebo-controlled study on the emergent awakening effects of zolpidem and zaleplon was conducted. Methods N = 34 participants (age M = 42.1 ± 9.7; 25 males; 9 Astronauts, 7 Astronaut candidates, and 18 Flight Controllers) were investigated for three nights separated by M = 10 days. They were randomized to ingestion of one of the following at lights out: placebo, 10 mg zaleplon, and either 5 mg (N = 20) or 10 mg (N = 14) zolpidem. They were awakened abruptly by alarm at the expected PK,max (1 hr after lights out for zaleplon; 1.5 hr for placebo/zolpidem). Participants were required to turn off the alarm and perform a cognitive test battery twice, separated by a 20–30 min reading break. They then returned to sleep and were awakened to perform the same cognitive tasks at an average of 6.7 hr after drug ingestion. Results Relative to placebo, the effects of 10 mg zaleplon and 5 mg zolpidem on cognitive performance were minor. In contrast, 10 mg zolpidem adversely affected cognitive throughput (p < 0.001), psychomotor vigilance (p < 0.001), working memory (p < 0.01), delayed word recall (p < 0.05), and subjective sleepiness (p < 0.01) at the first emergent awakening. At terminal awakening, neither cognitive performance nor subjective sleepiness was impaired after ingestion of zaleplon or zolpidem (5 mg and 10 mg) compared with placebo. Conclusions Presleep ingestion of sleep medications, especially 10 mg zolpidem, poses a risk for performance errors after emergent awakenings near the expected PK,max. Registration Optimize Astronaut Sleep Medication Efficacy and Individual Effects (clinicaltrials.gov ID NCT03526575).

• Publisher: Oxford University Press
• Subject: Acetamides - adverse effects / Acetamides - pharmacology / Adult / Astronauts / Cognition - drug effects / Cognition - physiology / Cognitive Dysfunction - chemically induced / Cognitive Dysfunction - diagnosis / Cognitive Dysfunction - psychology / Cross-Over Studies / Double-Blind Method / Female / Humans / Hypnotics and Sedatives - adverse effects / Hypnotics and Sedatives - pharmacology / Male / Middle Aged / Pyrimidines - adverse effects / Pyrimidines - pharmacology / Sleep / Sleep - drug effects / Sleep - physiology / Sleep Aids, Pharmaceutical - adverse effects / Sleep Aids, Pharmaceutical - pharmacology / Wakefulness - drug effects / Wakefulness - physiology / Zolpidem - adverse effects / Zolpidem - pharmacology