Depression: Current Therapy and ovel Anti-depressant Drug Targets

Abstract

Affective disorders such as depression and anxiety are a major cause of disability and place a burden on society from both economic and social perspectives. In spite of over 50 years of effort in drug discovery and development, a substantial increase in the efficacy of antidepressant therapies has not been achieved, although improvements in safety and tolerability have been observed in newer drug therapies. Despite the advances in the anti-depressant therapy with various serotonergic and noradrenergic agents, a substantial unmet medical need in the treatment of depressive illness remains. These needs range from efficacy in treatment resistant patients, to improved onset, to reductions in side effects such as emesis or sexual dysfunction. To address these needs, there are numerous combination therapies and novel targets that have been identified that may demonstrate improvements in one or more areas. At one end of the spectrum is combination therapies that maintain the benefits associated with standard anti-depressant drugs and at the other end more novel targets, such as neurotrophins (BDNF, IGF), based on recent findings that antidepressants induce neurogenesis could fit to the need of antidepressant therapy. This review summarizes the pathological detail of depression, current anti-depressant therapy and development of non-monoamine-based antidepressants, and provides a progress report on some of the most promising current strategies