Developing Effective Treatments for Psychiatric Diseases

The past few decades have seen concerted efforts by ‘‘Team Science’’—universities, Government, private foundations, industry, and advocacy groups—to find and develop better treatments for patients with mood disorders. Multiple technologies including genetics, proteomics, transcriptomics, optical genetics, and neuroimaging (to name a few) have been used to explore the pathophysiology of these disorders. While we have yet to produce a single antidepressant that is more effective than those introduced over the past 50 years, Team Science has also achieved significant breakthroughs. Most notably, until recently we expected to wait weeks or longer for our antidepressants to ‘‘kick in’’, leading to considerable patient suffering and increased suicide risk. In a massive paradigm shift, recent studies have demonstrated that the anesthetic agent ketamine, a glutamatergic modulator, produces a significant antidepressant, antisuicidal ideation, and anti-anhedonic response in merely hours. Treatments thatwork thisquicklycould dramatically reduce the cumulativemorbidity, disability, and excess death associated with recurrent and protracted episodes of depression.Now, thereareplentyofunknownsassociated with ketamine use over time including its impact on cognition and the possibility of addiction. But we have an extraordinary opportunity to bring our considerable scientific acumen to bear on reverse engineering ketamine and using that knowledge to identify its mechanism of action, resulting in new and promisingcandidatedrugsderived fromketaminewithout addictivepropertiesor problematic side effects. Indeed, the ‘‘ketamine story’’ has already led to a boom in basic, clinical, and translational research. We have not achieved a cure yet, but we are a few steps closer. Team Science can get us there. Fund Research for Cures