Unmet Needs in MDD

Andrew J. Cutler, MD: If I could summarize the first part of our discussion, it sounds like we need medicines that work faster; more broadly on more patients and address a broader range of symptoms; and ideally have less tolerability and safety issues. That’s a tall order.... Let’s talk a little bit about some of these unmet needs. Greg, you and I have done a ton of clinical trials; How are newly approved treatments or those in clinical trials aiming to fulfill these unmet needs?

Gregory Mattingly, MD: First of all, we’re looking at novel mechanisms. The day of just modulating monoamines, I think, is behind us at this point. Most of our new agents are looking at novel mechanisms. Many of those mechanisms focus on that GABA and glutamate interface, and what’s really exciting is if you go up to the NMDA [N-methyl-D-aspartate] receptor and cascade through the nerve cell and the pathways, there are medicines in development that are targeting each and every one of those cascade points. Can they work quicker? Can they have a faster onset, as Sagar said? A lot of these newer agents are what we call fast-acting antidepressants where we don’t see separation after 2 weeks or 4 weeks or 6 weeks. We may see separation after 2 or 3 days. Looking at residual symptoms. I’m doing a study right now, Andy, where its primary efficacy measure is not an improvement of depression, it’s an improvement of anhedonia. Can emotional blunting and anhedonia be moved and moved quickly with a new treatment option? Cognitive issues. Many of our current and newer agents are measuring processing speed. Can I actually help the brain to process information more quickly, more efficiently as I get people better with depression? So, I think those are exciting agents. Everything has to be tested to see if they really work and what are the adverse effects and what do we bring as far as both good news and bad news with the new agent? But it’s exciting to look at this field where a lot of new things are in development.

Andrew J. Cutler, MD: That is certainly true. And it sounds like we are looking at these medicines that work maybe farther downstream in the process, as you mentioned, we think maybe the monoamine is doing something that starts a process that ultimately may lead to this synaptogenesis and other things. And certainly, the discovery of ketamine has made us realize maybe we can work farther down that pathway and faster.

Transcript edited for clarity