The Vision of Vilazodone and Vortioxetine

https://slatestarcodex.com/2020/06/15/the-vision-of-vilazodone-and-vortioxetine/

I.

One of psychiatry's many embarrassments is how many of our drugs get discovered by accident. They come from random plants or shiny rocks or stuff Alexander Shulgin invented to get high.

But every so often, somebody tries to do things the proper way. Go over decades of research into what makes psychiatric drugs work and how they could work better. Figure out the hypothetical properties of the ideal psych drug. Figure out a molecule that matches those properties. Synthesize it and see what happens. This was the vision of vortioxetine and vilazodone, two antidepressants from the early 2010s. They were approved by the FDA, sent to market, and prescribed to millions of people. Now it's been enough time to look back and give them a fair evaluation. And…

…and it's been a good reminder of why we don't usually do this.

Enough data has come in to be pretty sure that vortioxetine and vilazodone, while effective antidepressants, are no better than the earlier medications they sought to replace. I want to try going over the science that led pharmaceutical companies to think these two drugs might be revolutionary, and then speculate on why they weren't. I'm limited in this by my total failure to understand several important pieces of the pathways involved, so I'll explain the parts I get, and list the parts I don't in the hopes that someone clears them up in the comments.