When I first started using computers, I was using one of these mouse wrist rests for a few years, thinking that it would be more ergonomic. I was very wrong.

Perhaps I wasn't using it properly, perhaps my desk was too high, but in any case I developed discomfort in my right wrist, which progressed into acute pain whenever I stretched my wrist backwards. I got rid of the wrist rest, but the pain wouldn't go away.
Eventually, and even though I'm right-handed, I moved the mouse to the left side (I still have it there) and the pain progressively dissipated. It took many months though, perhaps more than a year.
Getting used to left-hand mousing took a couple of weeks or so (it was very frustrating at first), but after that, I could use it equally well with both hands. Besides, due to the standard keyboard's asymmetry, the left side is closer to the center of the keyboard (even on a 60%) and it's a more ergonomic place for the mouse to be (at least for me).
Nowadays, I do extensible use of keyboard shortcuts (
vimium for browsing,
layer mappings for text editing, etc.) and only use the mouse when necessary. I hadn't had any pain in my hands ever since.