NOCTURNAL MELATONIN SECRETION AND SLEEP AFTER DOXEPIN ADMINISTRATION IN CHRONIC PRIMARY INSOMNIA

Nocturnal melatonin secretion and polysomnographic sleep patterns were investigated in ten patients with chronic primary insomnia (age 41.3 +/- 9.5 years) and in five healthy subjects (age 27.2 +/- 0.7 years) a fter either a single intravenous administration of 25 mg doxepin or pl acebo in a randomized, double-blind, and cross-over setting. In the pa tient group a third session was performed after a three-week open oral treatment with 25 mg doxepin daily. The single-dose administration of doxepin did not affect plasma melatonin concentrations in either the patients or the healthy subjects. After three weeks of oral doxepin in take by the patients, the area under the curve of total nocturnal plas ma melatonin concentration was significantly increased by 26% and the peak values were increased by 30%. Both after the single i.v. treatmen t as well as after long-term oral administration, doxepin also signifi cantly improved sleep latency, total sleep time, and sleep efficiency in the insomniacs as well as the healthy subjects, whereas the nocturn al wake time was decreased. These findings indicate that this tricycli c antidepressant not only improves sleep and but also preserves the se cretion of a hormone which is believed to play a special role in the c ircadian sleep-wake rhythm. Long-term doxepin treatment of chronic ins omniac patients not only improves sleep but also restores nocturnal me latonin secretion in these patients.