Effects of trazodone and imipramine on the biological rhythm: an analysis of sleep EEG and body core temperature.

Depression commonly involves abnormalities of the sleep-wake rhythm, the temperature rhythm, and other biological rhythms. The changes of these biological rhythms are caused in remission by medications. However, it has yet to be clarified whether the biological rhythms are changed as a result of recovery from depression or from the direct pharmacological effects of the antidepressants. Therefore, we have undertaken a study on the direct effects of the antidepressants trazodone and imipramine on the biological rhythms of healthy volunteers. The study involved 12 healthy male volunteers (ages 21 approximately 28 years, mean age 23.9+/-1.7 years) who had given written informed consent. Placebo, trazodone, and imipramine were each administered in a single blind manner four times a day, during the three-day study period. The total daily dosage of trazodone was 100 mg (50 mg in one subject), and of imipramine 40 mg (20 mg in one subject). Subjects were submitted to polysomnography (PSG) and body core temperature (rectal temperature) measurements during the study period. We compared the data concerning the antidepressants to those of the placebo. The results show that, with regard to the sleep rhythm, trazodone significantly increased slow wave sleep (SWS), but no changes were observed in REM (rapid eye movement) sleep. Imipramine significantly decreased REM sleep and prolonged the REM cycle. With regard to the temperature rhythm, trazodone showed a tendency to advance the appearance time of the minimal temperature. Imipramine significantly lowered the maximal temperature and decreased the difference between the maximal and the minimal temperature, but no changes in the phases were observed. Neither antidepressant had any effect on the temperature cycle. Trazodone and imipramine showed different effects on PSG. Furthermore, they had different effects on the temperature rhythm. The changes of the sleep-wake rhythm were greater than those of the temperature rhythm. Although the two antidepressants had different mechanisms of action, it is worthy of note that both directly influenced the biological rhythms of healthy volunteers.