Comparison of the residual effects of two benzodiazepines (nitrazepam and flurazepam hydrochloride) and pentobarbitone sodium on human performance.

Abstract

1 The residual effects of two benzodiazepines, nitrazepam (10 mg) and flurazepam hydrochloride (30 mg), and pentobarbitone sodium (200 mg) were studied by adaptive tracking and by reaction time. Performance was measured at 10 h, 13 h, 16 h, 19 h and 34 h after ingestion of each drug. Impaired performance on adaptive tracking was observed at 10 h, 13 h, 16 h and 19 h after nitrazepam and pentobarbitone sodium and at 10 h, 13 h and 16 h after flurazepam hydrochloride. Enhanced performance was observed at 34 h after nitrazepam and pentobarbitone sodium. 2 Increased reaction time persisted to 16 h after nitrazepam, flurazepam hydrochloride and pentobarbitone sodium and reaction time was also increased at 34 h after nitrazepam and pentobarbitone sodium. 3 During the morning immediately after ingestion, the subjects as a group were able to differentiate correctly between placebo and drugs, but they were not able to assess accurately the persistence of the residual effects of nitrazepam and pentobarbitone sodium. 4 Flurazepam hydrochloride would appear to be a more promising benzodiazepine than nitrazepam for use as a hypnotic by persons involved in skilled activity. There was a rapid recovery of performance during the afternoon and, unlike pentobarbitone sodium and nitrazepam, subjects retained the ability to recognize impaired skill.

Effect of Diazepam and Fosazepam (A Soluble Derivative of Diazepam) on Sleep in Man

“…On the morning after ingestion they felt they had fallen asleep quicker, and had slept better during the night. The subjects did not report increased sleepiness the morning after ingestion of the drugs, but such assessments related to residual effects of drugs may not be reliable (Borland & Nicholson, 1975a). The residual effects of 5-10 mg diazepam would be limited (Borland & Nicholson, 1975b), but, as the activity of fosazepam may be related to that of nordiazepam, it is likely that with fosazepam residual effects on performance would be present (Tansella, Zimmermann Tansella & Lader, 1974).…”

“…Little work has been carried out on the effectiveness of hypnotics at unusual times, but several studies have been concerned with residual effects on performance. Many hypnotics, including the benzodiazepines, lead to impaired performance after overnight ingestion (Malpas, Rowan, Joyce & Scott, 1970;Bond & Lader, 1972Borland & Nicholson, 1974, 1975aBorland, Nicholson & Wright, 1975), but it would appear that the persistence of impaired performance after diazepam is more limited than that after nitrazepam and flurazepam hydrochloride (Borland & Nicholson, 1975a & b). 35 Diazepam may be a particularly useful hypnotic, even though it has received little attention from sleep researchers except for the brief report of Kales & Scharf (1973).…”

Effect of the 1,5‐benzodiazepines, clobazam and triflubazam, on sleep in man.

“…In a previous study it was not possible to establish unequivocally even immediate effects of clobazam on performance (Borland & Nicholson, 1975b), and, even though the subjects reported impaired wakefulness during the morning after ingestion, it would appear that the adverse assessments are unlikely to be related to changes in performance. The overnight ingestion of clobazam would not lead to the residual sequelae observed with some of the 1,4-benzodiazepines (Bond & Lader, 1972, 1973Borland & Nicholson, 1975a), and so it may prove particularly useful for persons involved in skilled activity. These and the previous studies suggest that diazepam (5-10mg) and clobazam (10-20mg) are promising drugs for the management of disturbed sleep when impaired performance the next day would be unacceptable.…”

“…Many benzodiazepines with hypnotic properties have residual effects during the day after overnight ingestion (Bond & Lader, 1972, 1973& 1975Borland & Nicholson, 1975a), but the 1,4-benzodiazepine, diazepam, and the 1,5-benzodiazepine, clobazam, have less persistent sequelae (Caille & Bassano, 1974;Borland & Nicholson, 1975b). In previous studies we have examined the effects of diazepam, its principal metabolites, N-desmethyldiazepam (nordiazepam) and 3-hydroxydiazepam (temazepam), and other closely related benzodiazepines on sleep in man Nicholson, Stone, Clarke & Ferres, 1976), and it would appear that diazepam, or a closely related drug, may prove to be useful in the management of disturbed sleep and be appropriate for persons involved in skilled activity.…”

Performance studies with antihistamines.

“…In previous studies we have been concerned with the effect of benzodiazepines on human performance. Some benzodiazepines, commonly used as hypnotics, have persistent residual sequelae, and would be unacceptable if impaired performance the next day was to be avoided (Borland & Nicholson, 1975). However, impaired performance with other benzodiazepines, which nevertheless possess useful hypnotic activity Nicholson, Stone & Clarke, 1976), may be limited to the sleep period (Clarke & Nicholson, 1978), and so would be appropriate for persons involved in skilled activity.…”