New views on antidepressant action

The increasing incidence of depressive spectrum disorders worldwide, together with the failure of current medication to effectively treat a significant proportion of cases, calls for a better knowledge of the physiopathology of depression and of the therapeutic action of antidepressants. Recent research has unveiled an array of new mechanisms through which antidepressant drugs help restore neuronal plasticity and neurotransmission. In this review, we summarize the latest advances in the field, focusing on the effectors and molecular pathways that sustain the action of antidepressants. Grasping the overall brain response to antidepressants, with an integrated overview of the neurotransmitter systems, signaling cascades and neural circuits at play, should help to design more potent and selective therapies.

► Understanding how antidepressants exert their therapeutic effect remains a challenge.
► Antidepressant drugs help restore neuronal plasticity and neurotransmission.
► We review the molecular pathways involved in the action of antidepressants.
► We focus on neurogenesis, Wnt pathway, epigenetic mechanisms and circadian rhythms.