It is a puzzler, not having the development explained or explored on screen. But maybe having to fight Dean every step of the way actually helped keep Sam going with his research efforts, because having something tangible to fight against helped keep him angry and therefore prevented him sliding into despair. Since they've had their reconciliation and reached an understanding he doesn't have that any more. That confrontation in Fresh Blood was a turning point for Sam as well as for Dean, because it was the moment his own walls of denial came crashing down, the first time he admitted out lout that he might not be able to save his brother. So maybe without that anger and denial to fuel his stubborn determination to keep going, he's just completely lost all hope that there is any miracle out there to find. And thus he's hit absolute despair.

Poor boys :(