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

Abstract

The effects of 10 mg haloxazolam (HAX), 4 mg flunitrazepam (FNZ), and 0.5 mg triazolam (TRI), each administered for seven consecutive nights were studied in the sleep electroencephalograms (EEG) of 17 (six HAX, five FNZ and six TRI) healthy male student volunteers. Recordings of C3-A1 EEG data from one baseline night, three drug nights (first, fourth and seventh) and two withdrawal nights (second and fourth) were analyzed using a fast Fourier transformation method. All three drugs induced similar changes in the 0.5 Hz to 40 Hz power spectrum; namely (i) higher frequency (including the sigma and beta bands) activity increased and lower frequency activity reduced on the drug nights; (ii) the enhancement of sigma activity peaked during non-rapid eye movement sleep following the first administration and was maintained at high levels on all drug nights; (iii) beta activity increased through the night after administration of HAX and FNZ, but not TRI, which suggests a blood concentration level dependent increase of beta activity; and (iv) only HAX showed a residual effect on the fourth withdrawal night. These results indicate that (i) chronic administration of these three benzodiazepine derivatives produce similar profiles in sleep EEG spectral changes, with some differences depending on their half-lives and doses; (ii) the mechanism of sigma enhancement is sensitive to even the initial administration night of BDZ; and (iii) frequencies below and above the sigma band are less sensitive to BDZ and also show an increase through the night after administration, suggesting differences in the mechanisms reflected by these EEG frequency bands.