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

Various methods are used to quantify sedative drug effects, but it is unkno wn how these surrogate measures relate to clinically relevant sleepiness. T his study assessed the sensivity of different surrogates of sedation to cli nically relevant sleepiness induced by sleep deprivation. Nine healthy volu nteers completed a balanced three-way cross-over study with I-week wash-out periods. Adaptive tracking, smooth-pursuit and saccadic eye movements, bod y sway, digit symbol substitution (DSST), visual analogue scales (VAS) and electroencephalograms (EEG) were evaluated on three occasions: (1) during t he 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 gradu al decline at night and a constant average reduction of 38 percent [95% Con fidence intervals (CI), 28-47%] during the day after sleep deprivation. Ave rage mood scores diminished by 14 percent (95%, Cl 2-24%) during the day af ter sleep deprivation. Adaptive tracking saccadic eye movements and body sw ay tended to deteriorate at night, but overall this was not statistically s ignificant. After a night of sleep deprivation, adaptive tracking decreased by 21 percent (95% CI, 11-30%), saccadic eye movements decreased by 9-10 p ercent (95% CI, 5-13%/6-15%) and body sway increased by 37 percent (95% CI, 5-79%). In contrast, EEG beta(2)-amplitudes declined significantly at nigh t by 18 percent (95% CI, 6-29%), without changes during the day after sleep deprivation. Smooth pursuit, DSST and other EEC-amplitudes remained unchan ged. These results emphasize that reductions in adaptive tracking, saccadic peak velocity and body sway caused by sedative drugs really reflect sedati on. They also provide a level of clinical significance for these surrogates of sedation. EEG: parameters and smooth pursuit were unaffected by sleep d eprivation, so drug-induced changes in these measures may not reflect sedat ion in a stricter sense. The motivation and alertness necessary for DSST ma y overcome mild sedation.