Effects of the short-acting benzodiazepine triazolam, taken at bedtime, on circadian and sleep-related hormonal profiles in normal men.
Studies in rodents have shown that triazolam, a commonly used hypnotic, may shift circadian rhythms, with the direction and magnitude of the phase-shifts being dependent on the time of drug administration. To determine whether benzodiazepine, taken at standard bedtime, modifies the amount and/or temporal organization of hormonal secretion, six normal men were studied during basal conditions and on the first and third days of treatment with 0.5 mg triazolam. In each study, sleep was polygraphically monitored and plasma cortisol, growth hormone (GH), melatonin, and prolactin (PRL) (i.e., hormones influenced by circadian rhythmicity and/or sleep) were measured at 20-min intervals for 24 h. The sleep latency and the number and duration of awakenings were reduced during triazolam treatment as compared to baseline conditions. The only alteration of sleep architecture was a partial suppression of stages III + IV (SW) in late sleep. Triazolam did not affect the mean cortisol and melatonin levels or the total amount of GH secreted over the 24-h span. The circadian timings of the onsets of cortisol and melatonin secretions were essentially unaltered. The nocturnal rise of melatonin was prolonged by 45 to 60 minutes. Sleep-associated GH release was not modified by triazolam. Sleep-associated PRL secretion persisted, but in half of the nights studied was enhanced almost threefold. This effect of the drug on nocturnal PRL secretion was not specific to either the first or the third night of treatment, nor was it specific to certain subjects. Irrespective of the magnitude of the nocturnal elevation, morning PRL levels were slightly but consistently higher after triazolam treatment than under basal conditions. Normal PRL levels resumed around noon. In conclusion, administration of 0.5 mg triazolam at normal bedtime (2230) for three consecutive days may induce a transient hyperprolactinemia, but does not abolish sleep-related hormone secretion and does not affect the timing of endocrine events controlled by the circadian clock. These findings are consistent with studies in hamsters where treatment with triazolam in the early subjective night was also without effect on the rodent circadian clock.
Copinschi
G
G
School of Medicine, Free University of Brussels, Belgium.
Van Onderbergen
A
A
L'Hermite-Balériaux
M
M
Szyper
M
M
Caufriez
A
A
Bosson
D
D
L'Hermite
M
M
Robyn
C
C
Turek
F W
FW
Van Cauter
E
E
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects*; D006224:Cricetinae; D013006:Growth Hormone / Q000378:metabolism; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000378:metabolism; D008647:Mesocricetus; D011388:Prolactin / Q000378:metabolism; D012890:Sleep / Q000187:drug effects; D014229:Triazolam / Q000494:pharmacology*
D006728:Hormones; D014229:Triazolam; D011388:Prolactin; D013006:Growth Hormone; D008550:Melatonin; D006854:Hydrocortisone