Trimipramine: A challenge to current concepts on antidepressives

Although it is chemically a classical tricyclic antidepressant agent, trimipramine shows atypical pharmacological properties. Its well-documented antidepressant action cannot be explained by noradrenaline or serotonin reuptake inhibition or by a down-regulation of β-adrenoceptors. Furthermore, its receptor affinity profile resembles more that of clozapine, a neuroleptic drug, than that of tricyclic antidepressants. Trimipramine does not reduce, but rather increases, rapid eye movement sleep. It stimulates nocturnal prolactin secretion and inhibits nocturnal cortisol secretion, and may act at the level of the hypothalamus on corticotropin-releasing hormone secretion. Trimipramine is of particular value in depressed patients with insomnia, and it has been shown to be effective in the therapy of primary insomnia. As the pharmacological profile indicates, and an open clinical study has shown, trimipramine might also be active as an antipsychotic. The drug is both a tool for increasing our understanding of depression and a potential therapy for several psychiatric disorders.