Long time Thunderbird in Linux user, had to switch to Mutt a few months ago. Having 3 inboxes configured was taking, for some reason, +10Gb of disk and several Gb of RAM, plus being painfully slow and freeze pretty often.
My fix for most annoyances was to copy mail locally, and run dovecot locally on the same box as TB (TB doesn't support standard maildir). I also added a wrapper script that does a VACUUM on all the sqlite dbs in the profile when starting TB.
With the above, TB has worked well for me.
I have 15 GB of mail across 5 email accounts and Thunderbird is currently sitting at 350 MB RAM. Rarely crosses 500MB, I think.
I am encountering some freezes and occasional crashes which are annoying, but on linux there is nothing better.