Proof of concept trials in bipolar disorder and major depressive disorder: a translational perspective in the search for improved treatments.

A better understanding of the neurobiology of mood disorders, informed by preclinical research and bi-directionally translated to clinical research, is critical for the future development of new and effective treatments. Recently, diverse new targets/compounds have been specifically tested in preclinical models and in proof-of-concept studies, with potential relevance as treatments for mood disorders. Most of the evidence comes from case reports, case series, or controlled proof-of-concept studies, some with small sample sizes. These include (1) the opioid neuropeptide system, (2) the purinergic system, (3) the glutamatergic system, (4) the tachykinin neuropeptide system, (5) the cholinergic system (muscarinic system), and (6) intracellular signaling pathways. These targets may be of substantial interest in defining future directions in drug development, as well as in developing the next generation of therapeutic agents for the treatment of mood disorders. Overall, further study of these and similar drugs may lead to a better understanding of relevant and clinically useful drug targets in the treatment of these devastating illnesses.