Trimipramine and imipramine exert different effects on the sleep EEG and on nocturnal hormone secretion during treatment of major depression.
In a 4-week double-blind clinical trial we compared the effects of the tricyclic antidepressants trimipramine and imipramine on the sleep EEG and on nocturnal bormone secretion in 20 male inpatients with major depression. Both treatments produced rapid significant clinical improvement in depression without severe adverse effects. However, the two drugs had markedly different neurobiologic profiles. Trimipramine enhanced rapid eye movement (REM) sleep and slow wave sleep, whereas imipramine suppressed REM sleep and showed no effect on slow wave sleep. Total sleep time and the sleep efficiency index increased under trimipramine but not under imipramine. Nocturnal cortisol secretion decreased with trimipramine but remained unchanged with imipramine. In contrast to imipramine, trimipramine induced an increase in prolactin secretion compatible with its known antagonism at dopamine (D2) receptors. Imipramine induced a decrease in growth hormone secretion during the first half of the night. Neither of the drugs induced significant changes in plasma testosterone concentration. We conclude that trimipramine is an antidepressant with sleep-improving qualities that possibly acts through inhibition of hypothalamic-pituitary-adrenocortical system activity by a yet unknown mechanism.
Sonntag
A
A
Max Planck Institute of Psychiatry, Department of Psychiatry, Munich, Germany.
Rothe
B
B
Guldner
J
J
Yassouridis
A
A
Holsboer
F
F
Steiger
A
A
D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D065127:Dopamine D2 Receptor Antagonists; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007099:Imipramine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D017286:Polysomnography / Q000187:drug effects*; D011388:Prolactin / Q000097:blood*; D017448:Receptors, Dopamine D2 / Q000502:physiology; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D013739:Testosterone / Q000097:blood; D014299:Trimipramine / Q000009:adverse effects / Q000627:therapeutic use*
D000929:Antidepressive Agents, Tricyclic; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D019382:Human Growth Hormone; D013739:Testosterone; D014299:Trimipramine; D011388:Prolactin; D007099:Imipramine; D006854:Hydrocortisone