The sensitivity of pharmacodynamic tests for the central nervous system effects of drugs on the effects of sleep deprivation

• Published in: Journal of psychopharmacology (Oxford) 1999, Vol.13 (1), p.10-17
• Main Authors: van Steveninck, A. L., van Berckel, B. N. M., Schoemaker, R. C., Breimer, D. D., van Gerven, J. M. A., Cohen, A. F.
• Format: Article
• Language: English
• Subjects: Activity levels. Psychomotricity; Adult; Alertness; Biological and medical sciences; Central nervous system; Central Nervous System - drug effects; Clinical significance; Cognition - drug effects; Cross-Over Studies; Double-Blind Method; EEG; Electroencephalography; Electroencephalography - drug effects; Eye; Eye movements; Eye Movements - drug effects; Female; Fundamental and applied biological sciences. Psychology; Humans; Hypnotics. Sedatives; Male; Medical sciences; Mood; Motivation; Neuropharmacology; Pharmacodynamics; Pharmacology. Drug treatments; Posture - physiology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychomotor Performance - drug effects; Psychomotor Performance - physiology; Psychopharmacology; Saccadic eye movements; Sleep and wakefulness; Sleep deprivation; Sleep Deprivation - physiology; Sleepiness; Smooth pursuit eye movements; Statistical analysis; Time Factors; Vigilance. Attention. Sleep; Wakefulness
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/026988119901300102

Various methods are used to quantify sedative drug effects, but it is unknown how these surrogate measures relate to clinically relevant sleepiness. This study assessed the sensivity of different surrogates of sedation to clinically relevant sleepiness induced by sleep deprivation. Nine healthy volunteers completed a balanced three-way cross-over study with 1-week wash-out periods. Adaptive tracking, smooth-pursuit and saccadic eye movements, body sway, digit symbol substitution (DSST), visual analogue scales (VAS) and electroencephalograms (EEG) were evaluated on three occasions: (1) during the day after normal sleep, (2) during wakefulness at night; and (3) during the day after a night of sleep deprivation.VAS of alertness showed a gradual decline at night and a constant average reduction of 38 percent [95% Confidence intervals (CI), 28–47%] during the day after sleep deprivation. Average mood scores diminished by 14 percent (95%, CI 2–24%) during the day after sleep deprivation. Adaptive tracking, saccadic eye movements and body sway tended to deteriorate at night, but overall this was not statistically significant. After a night of sleep deprivation, adaptive tracking decreased by 21 percent (95% CI, 11–30%), saccadic eye movements decreased by 9–10 percent (95% CI, 5–13%/6–15%) and body sway increased by 37 percent (95% CI, 5–79%). In contrast, EEG b2-amplitudes declined significantly at night by 18 percent (95% CI, 6–29%), without changes during the day after sleep deprivation. Smooth pursuit, DSST and other EEG-amplitudes remained unchanged. These resultsemphasize that reductions in adaptive tracking, saccadic peak velocity and body sway caused by sedative drugs really reflect sedation. They also provide a level of clinical significance for these surrogates of sedation. EEG parameters and smooth pursuit were unaffected by sleep deprivation, so drug-induced changes in these measures may notreflect sedation in a stricter sense. The motivation and alertnessnecessary for DSST may overcome mild sedation.