Khandi Alexander leaves the show in the middle of the fourth season and after it's fourth season, the show is cancelled. Two weeks after it's cancellation, it's magically renewed for a fifth season. Ten days after that, Phil Hartman is murdered by his wife.
So, in the fifth season, you have two of the main characters leave the show.
In a sense, it gets a little weird and stale like Scrubs: Med School was.