In historical retrospect, Howard Hughes had a pretty good excuse for going off the rails in the 25 years prior to his death. He had screwed up his lower back in plane crashes much earlier and was prescribed an increasingly assorted amount of high powered medications (and self-prescribed) that affected his mental state.

The 1950s-early 1970s were not exactly a golden era of non-addictive totally harmless painkillers and other psychoactive pharmaceuticals. And if you had essentially unlimited money to spend on private doctors who would do whatever you wanted...

All of that, combined with whatever underlying bipolar or other psychological conditions he might have had, and Howard's predilection towards self-medicating himself, did not turn out to be a good combination.