Emerging drugs for major depressive disorder.

Most current pharmacologic antidepressant treatments target either or both serotonin and norepinephrine systems in the brain to alleviate depressive symptoms. However, > or = 30% of patients with major depressive disorder fail to respond to these antidepressants, inciting a need for alternative treatment strategies. In the past decade, there has been extensive research into improving the mechanism of action for monoamine agents as well as identifying novel treatment targets for depression. For monoamines, drugs that increase serotonin, norepinephrine, melatonin or dopamine have been explored as putative antidepressants and in some cases approved (agomelatine and desvenlafaxine). Novel drugs that act on amino acid receptors, neurotrophic factors, cytokines, neuropeptides and acetylcholine are also in development. This review will discuss the scientific rationale for these targets, as well as highlight the current status of drugs in development.