Effects of a Short-Acting Benzodiazepine on Brain Electrical Activity During Sleep

Abstract

1, SUMMARYThe changes seen in EEG activity with administration of long-acting benzodiazepines are a significant decrease In delta, 0.5-3 Hz, and a significant increase in sleep spindles, bursts of 11-15 Hz activity. These changes often persist for several days after the medication is discontinued.The introduction of a new benzodiazepine hypnotic, triazolam, in which the half-life of both the parent compound and its metabolite is less than 10 hours, raises questions as to whether its use will produce similar EEG changes during sleep and whether there will be a build-up effect over nights. Of particular interest is whether electrophysiological and performance changes will persist at the same level during a 7.5-hour sleep period and whether there will be a quick return to baseline EEG activity during withdrawal. As part of a larger study on the effects of benzodiazepines on EEG, sleep, arousal levels, and performance, delta and spindle activity were measured during baseline, treatment, and withdrawal. The auditory cortical evoked potential was also obtained during the last baseline and during the fifth drug night.Twenty male chronic poor sleepers, mean age 21.02 ± 2.37 years, with EEG measured sleep latencies of greater than 30 minutes, participated in the double-blind study. All received a placebo for 3 nights, 10 continued to receive the placebo and 10 were given 0.5 mg triazolam for 6 nights, and all received placebo on 2 withdrawal nights. Subjects received click stimulation on the last night of the baseline and the fifth night of hypnotic administration (study nights 4 and 9).Subjects receiving triazolam showed a significant increase in sleep spindles and a significant decrease in delta count during drug administration. Both values returned to baseline on the first withdrawal night. The auditory evoked potential (AEP) peak-to-trough amplitude was also significantly reduced during sleep by triazolam, but, as the time since drug ingestion increased, the amplitude of the AEP also increased. There was no difference in AEP amplitude between the two groups 5 hours post-drug ingestion.In morning performance batteries, there were no cognitive or visual motor performance decrements. While the long-acting metabolites of some benzodiazepines, further influenced by dose levels, may be the neuropharmacological basis for daytime performance decrements, these data indicate that the EEG changes occur in the absence of long-acting metabolites. As with flurazepam, there was no relationship between the EEG changes, sleep efficiency, and morning performance.2

Long‐, intermediate‐ and short‐acting benzodiazepine effects on human sleep EEG spectra

“…Unlike the progressive increases in beta activity across drug nights, sigma enhancement peaked immediately on the IDN for each BDZ and did not change significantly across the drug nights, except HAX which showed significances when 4DN and 7DN were compared with IDN. Thus, sigma enhancement appeared less related to plasma accumulations of these BDZ hypnotics, which is consistent with previous reports 19,20 . Although FNZ produced a distinctly peaked large enhancement in beta activity during REM periods as we previously reported 11 it was not significantly greater than that produced by HAX or TRI.…”

Disqualified and qualified poor sleepers: Subjective and objective variables.

“…Presleep heart rate (HR) was calculated by counting heart beats on the polygraphic record, obtaining 1-min samples every 2 min from the time of lights out to Stage 2 onset. Spindle rates and delta rates during sleep were obtained according to procedures described previously (Johnson & Spinweber, 1981; Johnson, Spinweber, Seidel, & Dement, 1983). Following the morning awakening, subjects were asked to estimate their laboratory sleep latencies and evaluate their nighttime sleep by responding to our Morning Questionnaire.…”

“…In our previous research on sleeping aids (Johnson & Spinweber, 1981; Spinweber & Johnson, 1982, 1983), we utilized questionnaire responses and laboratory polysomnography to select sleep-onset insomniacs for participation. On the Naval Health Research Center (NHRC) Sleep Questionnaire (Johnson & Spinweber, 1983), potential subjects identified themselves as poor or very poor sleepers, reported a usual sleep latency of at least 45 min and indicated that they had trouble falling asleep for over 6 months.…”

On the Distribution of REM and NREM Sleep Under Two Benzodiazepines with Comparable Receptor Affinity but Different Kinetic Properties

“…In both parts ofthe present study, this led to an increase in stage 2 of 59 % under lormetazepam and 68 % under triazolam (KaIes et al, 1976;Leibowitz and Sunshine, 1978). However, under benzodiazepines the increase in stage 2 is accompanied by an increase in spindie density, i.e., in sleep spind-Ies per minute of stage 2 (Borbely et al, 1983;Johnson and Spinweber, 1981 ;Johnson et al, 1983;MOn/i, 1981 ;Spinweber and Johnson, 1982). While spindie reduction rarely exceeded normal values to any significant extent under land 2 mg lormetazepam, it was 42 % above the norm under 0.5 mg triazolam and as much as 65 % above the norm under I mg.…”