I would hate to think of drugging a cat, but could something over the past day or so just spooked him? If you've seen improvement with the box, is it possible it might need to be changed and cleaned more? If Joey's box doesn't get scooped as often as he poops and it doen't get changed and cleaned every other day, he makes sure I see him SQUATTING in the corner of the living room. (He does not actually go, but gives me this HINT.) When Mona was around , if the box was not to her liking she would just pee over the edge. I wouldn't be above having him checked either, and watch to see if he is straining to urinate or licking himself a lot THERE. If he is GET TO THE VET IMMEDIATELY. Joey had a urinary tract blockage years ago and for a day or so before it became totally blocked he was doing this and I did not pick up on it. If I had not picked up on it that Saturday he wouldn't be here today.
Hope this helps.