Action of Trimipramine on Sleep and Pituitary Hormone Secretion

Trimipramine is unlike other antidepressants in that it does not suppress REM sleep and possesses an atypical pharmacological profile. This antidepressant was administered in the evening to 10 depressed patients at a dosage of 75 mg on night 1 with 25 mg increments each night, up to 200 mg on night 6 and at this dosage thereafter. Sleep parameters were measured at baseline and on nights 2, 11 and 21. On nights 11 and 21, there was a significantly improved sleep pattern as shown by increases in sleep period time, total sleep time and sleep efficiency, and there was a decrease in sleep onset latency. No suppression of REM sleep occurred, and an increase was even noted; this, however, may have been due to a particularly low baseline value. Subjective assessments in which self-ratings of sleep quality were used also demonstrated an improvement in sleep. In addition, the neuroendocrine effects of trimipramine were investigated in 8 healthy volunteers after a single oral 75 mg dose. After 3 hours, a significant fall in plasma cortisol concentration from 117 to 43 micrograms/L and a significant rise in plasma prolactin concentration from 6 to 16.3 micrograms/L were observed, but there was no significant effect on plasma human growth hormone concentration. These results further support the effectiveness of trimipramine therapy in normalising a disturbed sleep pattern in depressed patients, and it may be of use in non-depressed insomniacs. The acute neuroendocrine effects of trimipramine are similar to those observed with neuroleptics and further indicate its atypical pharmacological profile.