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

B. N. M. van Berckel

R. C. Schoemaker

Centre for Human Drug Research, Leiden University Hospital

D. D. Breimer

Centre for Human Drug Research, Leiden University Hospital; Leiden–Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, Leiden, The Netherlands

J. M. A. van Gerven

Centre for HumanDrug Research, Leiden University Hospital; Centre for Human Drug Research, Zernikedreef 10, 2333 CL Leiden, The Netherlands jg{at}chdr.nl

A. F. Cohen

Centre for Human Drug Research, Leiden University Hospital

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.

Key Words: electroencephalogram • healthy volunteers • psychomotor performance • sedation • sleep deprivation • subjective effects

Journal of Psychopharmacology, Vol. 13, No. 1, 10-17 (1999)
DOI: 10.1177/026988119901300102


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