Antidepressant Therapy for Depression: An Update

Depression is a chronic and debilitating mental disorder that often remains undertreated. It could be due to unclear understanding of pathophysiology and/or inconsistent efficacy of current pharmacotherapy. Since the discovery of the first effective medications in the late 1950s, a variety of agents have been developed, which are mainly based on correction of monoamine deficit. However, over time, many different strategies have been determined in an effort to improve the efficacy and reduce the untoward effects of the therapeutic intervention. This chapter compiles the relative efficacy and plausible mechanism of antidepressant activity of most current therapeutic approaches targeting a wide range of molecular and cellular pathways, implicated in the pathogenesis of depression. Emerging knowledge of key pathogenic mechanisms, such as the impairment of non-monoaminergic neurotransmission, in addition to monoaminergic neurotransmission, hypothalamic-pituitary-adrenal axis hyperactivity, alteration in neurogenesis signaling pathways, enhanced brain oxidative stress, and inflammatory activity, has led to a host of new molecular drug targets. Several of these have been validated through the preliminary use of lead compounds and therapeutic agents in animals and humans.