Future directions for pharmacotherapies for treatment-resistant bipolar disorder

Current pharmacological treatments for bipolar disorder (BD) are limited and efficacy has
historically been discovered through serendipity. There is now scope for new drug development,
focused on the underlying biology of BD that is not targeted by current therapies. The need for novel
treatments is urgent when considering treatment resistant BD, where current therapies have failed. While established
drugs targeting the monoamine systems continue to be worthwhile, new biological targets including inflammatory and
oxidative an nitrosative pathways, apoptotic and neurotrophic pathways, mitochondrial pathways, the N-methyl-Daspartate
(NMDA)–receptor complex, the purinergic system, neuropeptide system, cholinergic system and melatonin
pathways are all being identified as potential anchors for the discovery of new agents. Many agents are experimental and
efficacy data is limited, however further investigation may provide a new line for drug discovery, previously stalled by
lack of corporate interest.