Having only been on Wellbutrin, I can't speak to that except that it's not doing it's thing (why they haven't invented a happy pill yet is beyond me.....) so a Zoloft booster was added. I have been on Ambien long term and it lost it's effectiveness so I have to switch it out every so many months and then go back.
I think anybody builds up a tolerance level to anything. It's how our bodies are meant to function, really.
I also have added Omega 3's a while ago and saw some improvement. Plus it's good for a whole bunch of stuff....

I'm sure others with more experience will pipe in.

But I hear you on the good days/bad days dilemma. The good (which is a relative term, I know) days are nice, but when they are over you suffer more, because you get just a teasing taste....