History of the Discovery of Antidepressant Drugs

Abstract

The clinical introduction of the first two specifically antidepressant drugs took place during the 1950s: iproniazid, a monoamine-oxidase inhibitor that had been used in the treatment of tuberculosis, and imipramine, the first drug in the tricyclic antidepressant family. Both antidepressant drugs made two fundamental contributions to the development of psychiatry: one of a social-health nature, consisting in an authentic change in the psychiatric care of depressive patients; and the other of a purely pharmacological nature, since these agents have constituted an indispensable research tool for neurobiology and psychopharmacology, permitting, among other things, the postulation of the first aetiopathogenic hypotheses of depressive disorders. The clinical introduction of fluoxetine, a selective serotonin reuptake inhibitor, in the late 1980s, once again revolutionized therapy for depression, opening the way for new families of antidepressants. All of these antidepressants, like the rest of those currently available for clinical practice, except agomelatine, share the same action mechanism, which involves the modulation of monoaminergic neurotransmission at a synaptic level. However, the future of antidepressant therapy could be directed to the search of extraneuronal non-aminergic mechanisms or mechanisms that modulate the intraneuronal biochemical pathways.