Some game modifiers alter difficulty a bit. But there's one game modifier that changes the game a lot. "Navigator" (available only in advanced/roguelite). WIth this thing on, you have a map but you have no information where on the map you are (unless you use a map device on the wall).
Besides that, I do not plan to add extra hard difficulty, although I'd like to add something that could change specific rules of the game (be one-handed, health drops all the time but killing restores it a bit, etc). These are more like ideas for the time after release. And remember that there is also endless mode coming that may contain much harder missions/quests.