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Pierre Denise - One of the best experts on this subject based on the ideXlab platform.
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Residual Effects of hypnotic drugs in aging drivers submitted to simulated accident scenarios: an exploratory study
Psychopharmacology, 2009Co-Authors: Mohamed Meskali, Pierre Denise, Catherine Berthelon, Sullivan Marie, Marie-laure BoccaAbstract:Rationale: The Effects of hypnotic drugs on driving performance are most often evaluated on young healthy subjects by using a monotonous motorway driving test. The Effects of drugs in urban driving situations have not yet been evaluated in any age group. Our objectives were to assess Residual Effects of the most prescribed hypnotics, zolpidem and zopiclone, on older middle-age drivers' capacities in an urban situation. Materials and methods: Sixteen healthy subjects aged 55 to 65 years underwent this double-blind, balanced, cross-over study. Zopiclone (7.5 mg), zolpidem (10 mg), and flunitrazepam (1 mg; used as positive control) or a placebo were administered at each subject's home at 11:00 pm under the supervision of an investigator. The next morning, the subjects had to drive in a simulated urban environment where accident scenarios were introduced. Accident scenarios were implemented using data from real accident cases. Results: Hypnotics did not significantly increase the number of collisions. However, significantly higher speeds were found with zopiclone and flunitrazepam; moreover, zolpidem and zopiclone induced modifications of the lateral position of the car on the road. Conclusions: This study did not reveal any major Residual Effects of the hypnotics studied on driving performance in aging drivers. However, the urban driving situations used here for the first time in the evaluation of drugs revealed some modifications in driving habits which could lead to risky behavior. It thus appears that urban driving simulations are useful for gaining knowledge about the Effects of drugs on driving behavior. Simulation - Urban scenarios - Aging drivers - Hypnotic drugs - Residual Effects
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Residual Effects of zolpidem, zopiclone and flunitrazepam on the processing of visual information in driving context
European Review of Applied Psychology, 2008Co-Authors: Catherine Berthelon, A. De Longcamp, Antoine Coquerel, Pierre DeniseAbstract:Abstract Drivers who had taken hypnotic medications such as benzodiazepines are over-represented in road accidents. Experimental studies show that, even the day after, these drugs induce an impairment of real or simulated driving. To remedy the undesirable side-Effects of hypnotics, new families of such drugs have been developed, their Residual Effects on visual information processing functions are poorly documented. We therefore compared the Residual Effects of two hypnotics, zopiclone (7.5 mg) and zolpidem (10 mg), and those of an old one, flunitrazepam (1 mg), versus a placebo on the capacities of subjects to estimate their own speed of movement and to anticipate a situation of collision with another vehicle parked along their trajectory. We found no modification in the processing of visual information the day after taking an active molecule. As these perceptive tasks have been demonstrated to be sensitive to environmental and individual factors, we can conclude that own speed perception and time to collision estimation are not affected by the Residual Effects of the hypnotic drugs studied. Thus, the behavioural impairments observed in previous studies result from the alteration of other functions solicited when driving a vehicle.
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Residual Effects of flunitrazepam, zopiclone and zolpidem in elderly drivers submitted to simulated driving accidents
2007Co-Authors: Catherine Berthelon, Mohamed Meskali, Sullivan Marie, A Cocquerel, M Moessinger, M-l Bocca, Pierre DeniseAbstract:In Europe, about 10% of road traffic victims are under the influence of a psychotropic substance, including illicit drugs and medications, at the time of the accident. Among these drugs, benzodiazepines are often implicated in the occurrence of accidents in both young and elderly users (1, 2). Notably, benzodiazepines and related drugs can lead to drowsiness due to their Residual Effects, which may persist the day after a bedtime dose. Obviously, these symptoms depend on the duration of action of the molecule, explaining why drivers who have taken long half-life benzodiazepines are over-represented in road accidents (3). Although half-life is not the only determinant of a drug's duration of action and Residual Effects, the choice of hypnotic molecules with the shortest half-lives and the fewest Residual Effects on behavioural efficiency has become a challenge in the context of road safety. Zopiclone and zolpidem have thus rapidly become very frequently prescribed hypnotics and are among the five most frequently used in Europe (4).
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Do Zopiclone, Zolpidem and Flunitrazepam have Residual Effects on Simulated Task of Collision Anticipation?
Journal of psychopharmacology (Oxford England), 2003Co-Authors: C. Berthelon, Marie-laure Bocca, Pierre Denise, A. PottierAbstract:Few studies have addressed the modifications in visual information processing brought about by taking hypnotic substances. The present experiment with healthy subjects investigated the Residual Effects of taking a single night-time dose of hypnotics on collision anticipation capacities the next morning. Visual sequences simulated the movement of a driver approaching an intersection where another vehicle was arriving. Ten participants had to estimate, as quickly as possible, whether the other vehicle would arrive before or after them at the intersection. They were tested after having taken a capsule of zolpidem (10 mg), zopiclone (7.5 mg), flunitrazepam (1 mg) or a placebo. The results show no Residual Effects of the molecules. Only flunitrazepam, a benzodiazepine with a long half-life, appears to cause subjects to focus their attention on an element which, while relevant for the task (a road sign playing the role of a spatial reference), is not used correctly.
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Residual Effects of hypnotics on disengagement of spatial attention.
Journal of psychopharmacology (Oxford England), 2000Co-Authors: Marie-laure Bocca, Pierre DeniseAbstract:In an earlier study, we postulated that the Residual Effects of hypnotics could induce a spatial attention disengagement deficit independent of any decrease in alertness. To test this hypothesis, we compared the Residual Effects of zolpidem, zopiclone and flunitrazepam in two ocular saccade tests, gap and overlap. In the gap paradigm, the lateral target is illuminated 200 ms after the extinguishing of the central target. In the overlap paradigm, the central target stayed on when the lateral target was illuminated. Zopiclone increases latency in the overlap, but not in the gap test, which appears to be specific to a deficit of disengagement of spatial attention. Zopiclone impairs the saccadic precision in gap, but not in overlap, which may be interpreted as an impairment of visuospatial memory. The Effects of zolpidem are limited to visuospatial impairment. The Effects of flunitrazepam are massive and probably the results of a decrease in alertness.
Marie-laure Bocca - One of the best experts on this subject based on the ideXlab platform.
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Residual Effects of hypnotic drugs in aging drivers submitted to simulated accident scenarios: an exploratory study
Psychopharmacology, 2009Co-Authors: Mohamed Meskali, Pierre Denise, Catherine Berthelon, Sullivan Marie, Marie-laure BoccaAbstract:Rationale: The Effects of hypnotic drugs on driving performance are most often evaluated on young healthy subjects by using a monotonous motorway driving test. The Effects of drugs in urban driving situations have not yet been evaluated in any age group. Our objectives were to assess Residual Effects of the most prescribed hypnotics, zolpidem and zopiclone, on older middle-age drivers' capacities in an urban situation. Materials and methods: Sixteen healthy subjects aged 55 to 65 years underwent this double-blind, balanced, cross-over study. Zopiclone (7.5 mg), zolpidem (10 mg), and flunitrazepam (1 mg; used as positive control) or a placebo were administered at each subject's home at 11:00 pm under the supervision of an investigator. The next morning, the subjects had to drive in a simulated urban environment where accident scenarios were introduced. Accident scenarios were implemented using data from real accident cases. Results: Hypnotics did not significantly increase the number of collisions. However, significantly higher speeds were found with zopiclone and flunitrazepam; moreover, zolpidem and zopiclone induced modifications of the lateral position of the car on the road. Conclusions: This study did not reveal any major Residual Effects of the hypnotics studied on driving performance in aging drivers. However, the urban driving situations used here for the first time in the evaluation of drugs revealed some modifications in driving habits which could lead to risky behavior. It thus appears that urban driving simulations are useful for gaining knowledge about the Effects of drugs on driving behavior. Simulation - Urban scenarios - Aging drivers - Hypnotic drugs - Residual Effects
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Do Zopiclone, Zolpidem and Flunitrazepam have Residual Effects on Simulated Task of Collision Anticipation?
Journal of psychopharmacology (Oxford England), 2003Co-Authors: C. Berthelon, Marie-laure Bocca, Pierre Denise, A. PottierAbstract:Few studies have addressed the modifications in visual information processing brought about by taking hypnotic substances. The present experiment with healthy subjects investigated the Residual Effects of taking a single night-time dose of hypnotics on collision anticipation capacities the next morning. Visual sequences simulated the movement of a driver approaching an intersection where another vehicle was arriving. Ten participants had to estimate, as quickly as possible, whether the other vehicle would arrive before or after them at the intersection. They were tested after having taken a capsule of zolpidem (10 mg), zopiclone (7.5 mg), flunitrazepam (1 mg) or a placebo. The results show no Residual Effects of the molecules. Only flunitrazepam, a benzodiazepine with a long half-life, appears to cause subjects to focus their attention on an element which, while relevant for the task (a road sign playing the role of a spatial reference), is not used correctly.
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Residual Effects of hypnotics on disengagement of spatial attention.
Journal of psychopharmacology (Oxford England), 2000Co-Authors: Marie-laure Bocca, Pierre DeniseAbstract:In an earlier study, we postulated that the Residual Effects of hypnotics could induce a spatial attention disengagement deficit independent of any decrease in alertness. To test this hypothesis, we compared the Residual Effects of zolpidem, zopiclone and flunitrazepam in two ocular saccade tests, gap and overlap. In the gap paradigm, the lateral target is illuminated 200 ms after the extinguishing of the central target. In the overlap paradigm, the central target stayed on when the lateral target was illuminated. Zopiclone increases latency in the overlap, but not in the gap test, which appears to be specific to a deficit of disengagement of spatial attention. Zopiclone impairs the saccadic precision in gap, but not in overlap, which may be interpreted as an impairment of visuospatial memory. The Effects of zolpidem are limited to visuospatial impairment. The Effects of flunitrazepam are massive and probably the results of a decrease in alertness.
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Residual Effects of zolpidem 10 mg and zopiclone 7 5 mg versus flunitrazepam 1 mg and placebo on driving performance and ocular saccades
Psychopharmacology, 1999Co-Authors: Marie-laure Bocca, Le F Doze, M Pottier, Jean Lhoste, Olivier Etard, Pierre DeniseAbstract:Rationale: Studies report contradictory results concerning the Residual Effects of zolpidem and zopiclone. Moreover, Residual Effects of these compounds on healthy subjects have not yet been simultaneously assessed. Objective: The present study with healthy subjects investigated the Residual Effects of zolpidem 10 mg and zopiclone 7.5 mg on driving performance and on ocular saccade and compared them to those under flunitrazepam 1 mg and placebo. Methods: The study involved 16 subjects divided into two groups, a 9:00 a.m. group and a 11:00 a.m. group, in a balanced, double-blind, cross-over design. Results: In the 9:00 a.m. group, zolpidem had no Residual Effects while zopiclone and flunitrazepam both impaired driving performance (P < 0.001 for both) and increased saccadic latency (P < 0.005; P = 0.052, respectively). Zopiclone impaired driving performance 5 times less than did flunitrazepam. In the 11:00 a.m. group, zolpidem and zopiclone had no Residual Effects, while flunitrazepam increased saccadic latency (P = 0.065) but did not impair driving performance. Conclusions: Zopiclone and flunitrazepam had Residual Effects in the first part of the morning, whereas zolpidem had no Residual Effects. The hierarchical character of the Effects of the molecules differed according to the test administered. This is probably linked more to drug-induced specific alterations than to different sensitivities of the tests.
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Residual Effects OF ZOLDIPEM 10 MG AND ZOPICLONE 7.5 MG ON DRIVING PERFORMANCE AND OCULAR SACCADES
1997Co-Authors: Marie-laure Bocca, Pierre Denise, Olivier Etard, F. Le Doze, J. L’hoste, M PottierAbstract:Although quantifying the responsibility of hypnotic drugs as a cause of traffic accidents is a complex task, their consumption does indeed appear to increase involvement in traffic accidents. The impairment of alertness after taking benzodiazepines is well known. This is why the pharmaceutical companies have developed new families of hypnotics similar to benzodiazepines, such as imidazopyridines or cyclopyrrolones. Whilst the acute and chronic Effects of these compounds now appear to be firmly established, the same cannot be said for their Residual Effects. An open preliminary study on a driving simulator with Zolpidem 10 mg showed Residual Effects for a group performing the driving test at 9.00 am and the absence of Residual Effects for the 11.00 am group, the test being carried out in both cases 12 h after drug administration (Etard et al 1995). This result could have been due to an indirect chronobiological effect resulting in increased post-hypnotic inertia. The protocol followed in this study was adapted so as to bring out this effect. (A) For the covering abstract see IRRD 893732.
Alain Patat - One of the best experts on this subject based on the ideXlab platform.
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Differential Residual Effects of zaleplon and zopiclone on actual driving: a comparison with a low dose of alcohol.
Sleep, 2002Co-Authors: Annemiek Vermeeren, Isabelle Paty, Mona Darwish, Wim J. Riedel, Martin P.j. Van Boxtel, Alain PatatAbstract:STUDY OBJECTIVES: To compare Residual Effects of zaleplon 10 mg, zopiclone 7.5 mg, and placebo, and a social dose of alcohol on car driving, memory, and psychomotor performance. DESIGN: Two-part placebo controlled, crossover study. Part 1 was single blind, Part 2 double blind. SETTING: University research institute. PARTICIPANTS: Thirty healthy volunteers (15 men and 15 women, mean age 32 +/- 7 years) INTERVENTIONS: In Part 1 alcohol and alcohol-placebo drinks were administered around noon. In Part 2 single oral doses of zaleplon 10 mg, zopiclone 7.5 mg and placebo were administered at bedtime. MEASUREMENT AND RESULTS: A highway driving test, laboratory tests of word learning, critical tracking and divided attention, and subjective assessments of sleep, mood, and Effects of treatments on driving. Driving started 40 minutes after a second alcohol dose in Part 1, and 10 hours after drug intake in Part 2. The results demonstrated that alcohol, at average plasma concentrations of approximately 0.030 g/dl, significantly impaired performance in all tests. Zaleplon's Residual Effects did not differ significantly from those of placebo in any test. In contrast, zopiclone had significant Residual Effects on driving, divided attention, and memory. The magnitude of impairment in the driving test observed the morning after zopiclone 7.5 mg was twice that observed with alcohol. CONCLUSION: Zaleplon 10 mg has no Residual Effects on driving when taken at bedtime, 10 hours before driving. In contrast, zopiclone 7.5 mg can cause marked Residual impairment. Patients should be advised to avoid driving the morning after zopiclone administration. Language: en
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Noise-induced sleep maintenance insomnia: hypnotic and Residual Effects of zaleplon
British journal of clinical pharmacology, 2002Co-Authors: Barbara M. Stone, Alain Patat, Isabelle Paty, Claire Turner, Sue L. Mills, Mona Darwish, Philippe DanjouAbstract:Aims The primary objective of the study was to assess the Residual Effects of zaleplon in the morning, 4 h after a middle-of-the-night administration. The secondary objective was to investigate the effectiveness of zaleplon in promoting sleep in healthy volunteers with noise-induced sleep maintenance insomnia. Methods Thirteen healthy male and female volunteers (aged 20–30 years) with normal hearing, who were sensitive to the sleep-disrupting Effects of noise, participated in a double-blind, placebo- and active-drug controlled, four-period cross-over study. The subjects were permitted to sleep for 5 h (22.45–03.45 h) in a quiet environment before they were awoken. At 04.00 h they ingested 10 mg zaleplon, 20 mg zaleplon, 7.5 mg zopiclone (active control), or placebo before a second period of sleep (04.00–08.00 h), during which they were exposed to an 80 dB(A) 1 kHz pure tone pulse with an inter-tone interval of 1 s and a duration of 50 ms. The sound stimulus was stopped after 10 min of persistent sleep or after 2 h if the subject had not fallen asleep. Residual Effects were assessed at 08.00 h (4 h after drug administration) using the digit symbol substitution test (DSST), choice reaction time (CRT), critical flicker fusion (CFF), and immediate and delayed free recall of a 20 word list. The data were analysed by analysis of variance. A Bonferroni adjustment was made for the three active treatments compared with placebo. Results There were no Residual Effects of zaleplon (10 and 20 mg) compared with placebo. Zopiclone impaired memory by delaying the free recall of words (P = 0.001) and attenuated performance on DSST (P = 0.004) and CRT (P = 0.001), compared with placebo. Zaleplon reduced the latency to persistent sleep (10 mg, P = 0.001; 20 mg, P = 0.014) and the 20 mg dose reduced stage 1 sleep (P = 0.012) compared with placebo. Zopiclone reduced stage 1 sleep (P = 0.001), increased stage 3 sleep (P = 0.0001) and increased total sleep time (P = 0.003), compared with placebo. Conclusions Zaleplon (10 mg and 20 mg), administered in the middle of the night 4 h before arising, shortens sleep onset without impairing next-day performance.
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Residual Effects of zaleplon and zolpidem following middle of the night administration five hours to one hour before awakening.
Human psychopharmacology, 2001Co-Authors: Ian Hindmarch, Alain Patat, Neil Stanley, Isabelle Paty, Una RigneyAbstract:The objective was to assess Residual Effects of zaleplon and zolpidem after a middle of the night administration. This was a randomized, double-blind, placebo-controlled, crossover study, conducted in 40 healthy young male and female subjects. Subjects were awakened in the middle of the night and administered either placebo or zaleplon 10 or 20 mg or zolpidem 10 mg. A battery of objective tests exploring psychomotor and cognitive functions such as critical flicker fusion (CFF), choice reaction time (CRT), digit symbol substitution test (DSST), and memory tests (Sternberg memory scanning and a word list) were administered immediately after morning waking. Zaleplon 10 mg was devoid of Residual Effects whatever - the time of dosing - except a minimal but significant decrease in DSST scores when administered 1 h before awakening. Zaleplon 20 mg produced significant Residual Effects on performance (increase in CRT, and decrease in CFF threshold and in DSST scores) and memory (decrease in immediate and delayed free recall of words) only when administered 1 h before awakening. In contrast, zolpidem 10 mg produced significant detrimental Residual Effects on CRT and delayed free recall of words, when administered up to 5 h before waking, on DSST and Sternberg when administered up to 3 h before awakening and on CFF when administered 1 h before awakening. The Residual Effects of zolpidem 10 mg were more marked than those observed after zaleplon 20 mg. The present results demonstrate that zaleplon 10 mg has no or minimal Residual Effects when administered in the middle of the night as little as 1 h before waking. The lack of clinically significant Residual Effects with zaleplon may be explained by its unique pharmacokinetic (rapid elimination half-life) and pharmacodynamic (selective binding for GABA(A) receptors with the alpha(1) subunit, dissociation between sleep inducing properties and impairment of cognitive functions) profiles. Copyright 2001 John Wiley & Sons, Ltd.
P. N. Takkar - One of the best experts on this subject based on the ideXlab platform.
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Residual Effects of phosphorus applied to soyabean or wheat in a soyabean–wheat cropping system on a typic haplustert
The Journal of Agricultural Science, 1996Co-Authors: A. Subba Rao, K. Sammi Reddy, P. N. TakkarAbstract:During a 3-year experimental period (between 1992 and 1995), Residual Effects on yields of subsequent crops of phosphorus applied either to soyabean or wheat, and on recoveries of the added P and changes in the available P, were studied in a soyabean-wheat cropping system on a typic haplustert very low in available P at Bhopal, India. Phosphorus was applied at rates of 0-52 kg P ha -1 (five treatments) to soyabean and 0-39 kg P ha -1 (three treatments) to wheat during the first year, and in the subsequent years the Residual Effects were studied in relation to fresh applications of 39 kg P ha -1 to each crop. The yields of soyabean and wheat were increased significantly by the application of P to each crop. Phosphorus applied to soyabean showed Residual Effects in two succeeding crops, whereas P applied to wheat showed a Residual effect in only one succeeding crop. Phosphorus applied to soyabean was more efficiently utilized by the succeeding crops compared to that applied to wheat in the rotation. The recoveries of added P were greater with smaller rates of added P and greater in the first two Residual crops. Olsen P in soil was adequate only in the first year and it fell below the critical limit in the subsequent two cycles of cropping. Cumulative P uptake by crops determined the levels of available P in the soil and soil test values declined with increase in cumulative P uptake over time.
Isabelle Paty - One of the best experts on this subject based on the ideXlab platform.
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Differential Residual Effects of zaleplon and zopiclone on actual driving: a comparison with a low dose of alcohol.
Sleep, 2002Co-Authors: Annemiek Vermeeren, Isabelle Paty, Mona Darwish, Wim J. Riedel, Martin P.j. Van Boxtel, Alain PatatAbstract:STUDY OBJECTIVES: To compare Residual Effects of zaleplon 10 mg, zopiclone 7.5 mg, and placebo, and a social dose of alcohol on car driving, memory, and psychomotor performance. DESIGN: Two-part placebo controlled, crossover study. Part 1 was single blind, Part 2 double blind. SETTING: University research institute. PARTICIPANTS: Thirty healthy volunteers (15 men and 15 women, mean age 32 +/- 7 years) INTERVENTIONS: In Part 1 alcohol and alcohol-placebo drinks were administered around noon. In Part 2 single oral doses of zaleplon 10 mg, zopiclone 7.5 mg and placebo were administered at bedtime. MEASUREMENT AND RESULTS: A highway driving test, laboratory tests of word learning, critical tracking and divided attention, and subjective assessments of sleep, mood, and Effects of treatments on driving. Driving started 40 minutes after a second alcohol dose in Part 1, and 10 hours after drug intake in Part 2. The results demonstrated that alcohol, at average plasma concentrations of approximately 0.030 g/dl, significantly impaired performance in all tests. Zaleplon's Residual Effects did not differ significantly from those of placebo in any test. In contrast, zopiclone had significant Residual Effects on driving, divided attention, and memory. The magnitude of impairment in the driving test observed the morning after zopiclone 7.5 mg was twice that observed with alcohol. CONCLUSION: Zaleplon 10 mg has no Residual Effects on driving when taken at bedtime, 10 hours before driving. In contrast, zopiclone 7.5 mg can cause marked Residual impairment. Patients should be advised to avoid driving the morning after zopiclone administration. Language: en
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Noise-induced sleep maintenance insomnia: hypnotic and Residual Effects of zaleplon
British journal of clinical pharmacology, 2002Co-Authors: Barbara M. Stone, Alain Patat, Isabelle Paty, Claire Turner, Sue L. Mills, Mona Darwish, Philippe DanjouAbstract:Aims The primary objective of the study was to assess the Residual Effects of zaleplon in the morning, 4 h after a middle-of-the-night administration. The secondary objective was to investigate the effectiveness of zaleplon in promoting sleep in healthy volunteers with noise-induced sleep maintenance insomnia. Methods Thirteen healthy male and female volunteers (aged 20–30 years) with normal hearing, who were sensitive to the sleep-disrupting Effects of noise, participated in a double-blind, placebo- and active-drug controlled, four-period cross-over study. The subjects were permitted to sleep for 5 h (22.45–03.45 h) in a quiet environment before they were awoken. At 04.00 h they ingested 10 mg zaleplon, 20 mg zaleplon, 7.5 mg zopiclone (active control), or placebo before a second period of sleep (04.00–08.00 h), during which they were exposed to an 80 dB(A) 1 kHz pure tone pulse with an inter-tone interval of 1 s and a duration of 50 ms. The sound stimulus was stopped after 10 min of persistent sleep or after 2 h if the subject had not fallen asleep. Residual Effects were assessed at 08.00 h (4 h after drug administration) using the digit symbol substitution test (DSST), choice reaction time (CRT), critical flicker fusion (CFF), and immediate and delayed free recall of a 20 word list. The data were analysed by analysis of variance. A Bonferroni adjustment was made for the three active treatments compared with placebo. Results There were no Residual Effects of zaleplon (10 and 20 mg) compared with placebo. Zopiclone impaired memory by delaying the free recall of words (P = 0.001) and attenuated performance on DSST (P = 0.004) and CRT (P = 0.001), compared with placebo. Zaleplon reduced the latency to persistent sleep (10 mg, P = 0.001; 20 mg, P = 0.014) and the 20 mg dose reduced stage 1 sleep (P = 0.012) compared with placebo. Zopiclone reduced stage 1 sleep (P = 0.001), increased stage 3 sleep (P = 0.0001) and increased total sleep time (P = 0.003), compared with placebo. Conclusions Zaleplon (10 mg and 20 mg), administered in the middle of the night 4 h before arising, shortens sleep onset without impairing next-day performance.
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Residual Effects of zaleplon and zolpidem following middle of the night administration five hours to one hour before awakening.
Human psychopharmacology, 2001Co-Authors: Ian Hindmarch, Alain Patat, Neil Stanley, Isabelle Paty, Una RigneyAbstract:The objective was to assess Residual Effects of zaleplon and zolpidem after a middle of the night administration. This was a randomized, double-blind, placebo-controlled, crossover study, conducted in 40 healthy young male and female subjects. Subjects were awakened in the middle of the night and administered either placebo or zaleplon 10 or 20 mg or zolpidem 10 mg. A battery of objective tests exploring psychomotor and cognitive functions such as critical flicker fusion (CFF), choice reaction time (CRT), digit symbol substitution test (DSST), and memory tests (Sternberg memory scanning and a word list) were administered immediately after morning waking. Zaleplon 10 mg was devoid of Residual Effects whatever - the time of dosing - except a minimal but significant decrease in DSST scores when administered 1 h before awakening. Zaleplon 20 mg produced significant Residual Effects on performance (increase in CRT, and decrease in CFF threshold and in DSST scores) and memory (decrease in immediate and delayed free recall of words) only when administered 1 h before awakening. In contrast, zolpidem 10 mg produced significant detrimental Residual Effects on CRT and delayed free recall of words, when administered up to 5 h before waking, on DSST and Sternberg when administered up to 3 h before awakening and on CFF when administered 1 h before awakening. The Residual Effects of zolpidem 10 mg were more marked than those observed after zaleplon 20 mg. The present results demonstrate that zaleplon 10 mg has no or minimal Residual Effects when administered in the middle of the night as little as 1 h before waking. The lack of clinically significant Residual Effects with zaleplon may be explained by its unique pharmacokinetic (rapid elimination half-life) and pharmacodynamic (selective binding for GABA(A) receptors with the alpha(1) subunit, dissociation between sleep inducing properties and impairment of cognitive functions) profiles. Copyright 2001 John Wiley & Sons, Ltd.
