Chronobiological research on antidepressant drugs: the effect of the antidepressant drugs, trazodone and imipramine on the circadian rhythm using electroencephalography in healthy volunteers

Abstract

The effects of the antidepressant drugs trazodone and imipramine on the circadian rhythm were studied by means of the sleep propensity test (SPT; sleep latency was examined by 35-minute EEG records at 09:00, 11:00, 13:00, 15:00, 17:00). The subjects were 11 healthy male volunteers (mean age, 23.6 years old). The drugs were administered 4 times a day with single blind trials using an inactive placebo as a control. The dosages of the drugs were trazodone 50-100 mg/day and imipramine 20-40 mg/day. We discussed the circadian rhythm referring to previous polysomnograhy (PSG) studies using the same drugs and dosages with most of the same subjects. As a result, the mean sleep latency of SPT was the shortest at 09:00 (p<0.1) with a placebo, at 11:00 (p<0.05) with trazodone and at 13: 00 (not significantly) with imipramine administration. These results suggested that neither drug affected sleepiness. They affected the circadian rhythm during the daytime (=the day rhythm). They delayed the day rhythm. Delay of the day rhythm was due to trazodone and have been caused by not only trazodon administration itself, but also by the increase of slow-wave sleep obtained in the previous night's PSG study. And the day-rhythm delay was due to imipramine and might have been caused by not only imipramine administration itself, but also by the decrease in the percentage of slow-wave sleep and REM sleep, and an increase in REM latency obtained in the previous night's PSG study. Therefore, we concluded that neither drug affected the tendency toward sleepiness, but did affect the day rhythm in healthy subjects.