[New perspectives in the serotoninergic treatment for depression]

A great deal of data support the view that depression is frequently associated with a decrease in central serotonergic neurotransmission. Furthermore, this neurobiological alteration very probably contributes to depression because treatments known to increase the 'serotonergic tone', such as the chronic administration of selective serotonin reuptake inhibitors (SSRIs), have antidepressant properties. Extensive studies of the mechanisms of action of SSRIs led to the discovery of the key role of somato-dendritic 5-HT1A autoreceptors in a negative control of serotonergic neurotransmission. From this finding, a new treatment of depression has been attempted which consists of the association of an SSRI with an antagonist (non-selective) of these autoreceptors. The potent antidepressant action of this association (with a shorter delay of action, even in depressed patients previously resistant to 'classical' therapies) should promote novel therapeutic strategies consisting of raising the 'serotonergic tone' by acting on different (but convergent) molecular targets.